BioMed Research International: Biomaterials The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. In Vitro and In Vivo Response to Low-Modulus PMMA-Based Bone Cement Thu, 20 Aug 2015 16:17:29 +0000 The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated. Elin Carlsson, Gemma Mestres, Kiatnida Treerattrakoon, Alejandro López, Marjam Karlsson Ott, Sune Larsson, and Cecilia Persson Copyright © 2015 Elin Carlsson et al. All rights reserved. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release Thu, 13 Aug 2015 14:00:08 +0000 Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. Jingqiong Lu, Yinhui Li, Deng Hu, Xiaoling Chen, Yongmei Liu, Liping Wang, and Yansheng Zhao Copyright © 2015 Jingqiong Lu et al. All rights reserved. Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors Tue, 11 Aug 2015 05:50:26 +0000 Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instable in vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factors in vivo has become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor’s application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches. Hai-yang Zhao, Jiang Wu, Jing-jing Zhu, Ze-cong Xiao, Chao-chao He, Hong-xue Shi, Xiao-kun Li, Shu-lin Yang, and Jian Xiao Copyright © 2015 Hai-yang Zhao et al. All rights reserved. Erratum to “Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury” Tue, 28 Jul 2015 11:22:45 +0000 Wei Zhang, Yuan Gao, Yan Zhou, Jianheng Liu, Licheng Zhang, Anhua Long, Lihai Zhang, and Peifu Tang Copyright © 2015 Wei Zhang et al. All rights reserved. New Biomaterials and Regenerative Medicine Strategies in Periodontology, Oral Surgery, Esthetic and Implant Dentistry Mon, 27 Jul 2015 15:01:11 +0000 David M. Dohan Ehrenfest, Hom-Lay Wang, Jean-Pierre Bernard, and Gilberto Sammartino Copyright © 2015 David M. Dohan Ehrenfest et al. All rights reserved. Histological and Histomorphometric Human Results of HA-Beta-TCP 30/70 Compared to Three Different Biomaterials in Maxillary Sinus Augmentation at 6 Months: A Preliminary Report Sun, 26 Jul 2015 13:04:59 +0000 Objective. The aim of this investigation was to examine the bone regenerative potential of newly biphasic calcium phosphate ceramics (HA-β-TCP 30/70), by assessing histological and histomorphometric results of human specimens retrieved from sinuses augmented with HA-β-TCP 30/70, and comparing them to anorganic bovine bone (ABB), mineralized solvent-dehydrated bone allograft (MSDBA), and equine bone (EB), after a healing period of 6 months. Materials and Methods. Four consecutive patients with edentulous atrophic posterior maxilla were included in this report. A two-stage procedure was carried out for sinus augmentation with HA-β-TCP 30/70, ABB, MSDBA, and EB. After 6 months, specimens were retrieved at the time of implant placement and processed for histological and histomorphometric analyses. Results. At histological examination, all biomaterials were in close contact with the newly formed bone and showed the same pattern of bone formation; the grafted granules were surrounded by a bridge-like network of newly formed bone. A limited number of ABB particles were partially covered by connective tissue. The histomorphometric analysis revealed 30.2% newly formed bone for Ha-β-TCP 30/70, 20.1% for ABB, 16.4% for MSDBA, and 21.9% for EB. Conclusions. Within the limitations of the present investigation, these results support the successful use of HA-β-TCP 30/70 for sinus augmentation. Susanna Annibali, Giovanna Iezzi, Gian Luca Sfasciotti, Maria Paola Cristalli, Iole Vozza, Carlo Mangano, Gerardo La Monaca, and Antonella Polimeni Copyright © 2015 Susanna Annibali et al. All rights reserved. Oral Streptococci Biofilm Formation on Different Implant Surface Topographies Sun, 26 Jul 2015 08:47:31 +0000 The establishment of the subgingival microbiota is dependent on successive colonization of the implant surface by bacterial species. Different implant surface topographies could influence the bacterial adsorption and therefore jeopardize the implant survival. This study evaluated the biofilm formation capacity of five oral streptococci species on two titanium surface topographies. In vitro biofilm formation was induced on 30 titanium discs divided in two groups: sandblasted acid-etched (SAE- ) and as-machined (M- ) surface. The specimens were immersed in sterilized whole human unstimulated saliva and then in fresh bacterial culture with five oral streptococci species: Streptococcus sanguinis, Streptococcus salivarius, Streptococcus mutans, Streptococcus sobrinus, and Streptococcus cricetus. The specimens were fixed and stained and the adsorbed dye was measured. Surface characterization was performed by atomic force and scanning electron microscopy. Surface and microbiologic data were analyzed by Student’s -test and two-way ANOVA, respectively (). S. cricetus, S. mutans, and S. sobrinus exhibited higher biofilm formation and no differences were observed between surfaces analyzed within each species (). S. sanguinis exhibited similar behavior to form biofilm on both implant surface topographies, while S. salivarius showed the lowest ability to form biofilm. It was concluded that biofilm formation on titanium surfaces depends on surface topography and species involved. Pedro Paulo Cardoso Pita, José Augusto Rodrigues, Claudia Ota-Tsuzuki, Tatiane Ferreira Miato, Elton G. Zenobio, Gabriela Giro, Luciene C. Figueiredo, Cristiane Gonçalves, Sergio A. Gehrke, Alessandra Cassoni, and Jamil Awad Shibli Copyright © 2015 Pedro Paulo Cardoso Pita et al. All rights reserved. Influence of Leukocyte- and Platelet-Rich Fibrin (L-PRF) in the Healing of Simple Postextraction Sockets: A Split-Mouth Study Sun, 26 Jul 2015 08:17:48 +0000 The aim of this study was to evaluate the effects of leukocyte- and platelet-rich fibrin (L-PRF) on the pain and soft tissue healing after tooth extractions. Twenty-six patients (9 males and 17 females) were treated with multiple extractions (2 to 8), with a total of 108 extractions. This was an exploratory single blinded randomized clinical trial with a split-mouth design. The pain after the surgery was assessed in each patient by the VAS scale (1 to 10) at intervals of 24-48-72-96 hours. The soft tissue healing was clinically evaluated at 3, 7, 14, and 21 days after surgery by the same examiner surgeon, using the modified Healing Index (4 to 12). The mean value of postextraction pain was 3.2 ± 0.3 in the experimental sides and 4.1 ± 0.1 in the control sides. After 7 days from the extractions, the values of modified Healing Index in the experimental and control groups were, respectively, 4.8 ± 0.6 and 5.1 ± 0.9. The use of L-PRF in postextraction sockets filling can be proposed as a useful procedure in order to manage the postoperative pain and to promote the soft tissue healing process, reducing the early adverse effects of the inflammation. Gaetano Marenzi, Francesco Riccitiello, Mariano Tia, Alessandro di Lauro, and Gilberto Sammartino Copyright © 2015 Gaetano Marenzi et al. All rights reserved. Innate Immunity and Biomaterials at the Nexus: Friends or Foes Sun, 12 Jul 2015 11:12:45 +0000 Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body response: an acute sterile inflammatory reaction which overlaps with tissue vascularisation and remodelling and ultimately fibrotic encapsulation of the biomaterial to prevent further interaction with host tissue. Severity and clinical manifestation of the biomaterial-induced foreign body response are different for each biomaterial, with cases of incompatibility often associated with loss of function. However, unravelling the mechanisms that progress to the formation of the fibrotic capsule highlights the tightly intertwined nature of immunological responses to a seemingly noncanonical “antigen.” In this review, we detail the pathways associated with the foreign body response and describe possible mechanisms of immune involvement that can be targeted. We also discuss methods of modulating the immune response by altering the physiochemical surface properties of the biomaterial prior to implantation. Developments in these areas are reliant on reproducible and effective animal models and may allow a “combined” immunomodulatory approach of adapting surface properties of biomaterials, as well as treating key immune pathways to ultimately reduce the negative consequences of biomaterial implantation. Susan N. Christo, Kerrilyn R. Diener, Akash Bachhuka, Krasimir Vasilev, and John D. Hayball Copyright © 2015 Susan N. Christo et al. All rights reserved. Nanostructures Control the Hepatocellular Responses to a Cytotoxic Agent “Cisplatin” Sun, 12 Jul 2015 10:53:32 +0000 In drug discovery programs, the alteration between in vivo and in vitro cellular responses to drug represents one of the main challenges. Since the variation in the native extracellular matrix (ECM) between in vivo and 2D in vitro conditions is one of the key reasons for such discrepancies, thus the utilization of substrate that likely mimics ECM characteristics (topography, stiffness, and chemical composition) is needed to overcome such problem. Here, we investigated the role of substrate nanotopography as one of the major determinants of hepatic cellular responses to a chemotherapeutic agent “cisplatin.” We studied the substratum induced variations in cisplatin cytotoxicity; a higher cytotoxic response to cisplatin was observed for cells cultured on the nanopattern relative to a flat substrate. Moreover, the nanofeatures with grating shapes that mimic the topography of major ECM protein constituents (collagen) induced alterations in the cellular orientation and chromatin condensation compared to flat surfaces. Accordingly, the developments of biomimetic substrates with a particular topography could have potentials in drug development analyses to reflect more physiological mimicry conditions in vitro. Shimaa A. Abdellatef, Riho Tange, Takeshi Sato, Akihiko Ohi, Toshihide Nabatame, and Akiyoshi Taniguchi Copyright © 2015 Shimaa A. Abdellatef et al. All rights reserved. Gold Nanoparticles Promote Oxidant-Mediated Activation of NF-κB and 53BP1 Recruitment-Based Adaptive Response in Human Astrocytes Tue, 23 Jun 2015 13:31:42 +0000 Nanogold-based materials are promising candidate tools for nanobased medicine. Nevertheless, no conclusive information on their cytotoxicity is available. In the present study, we investigated the effects of gold nanoparticles (AuNPs) on human astrocytes in vitro. Nanogold treatment in a wide range of concentrations did not result in cytotoxicity. In contrast, nanogold provoked changes in the astrocyte cell cycle and induced senescence-associated β-galactosidase activity. AuNPs promoted oxidative stress and caused activation of NF-κB pathway. After nanogold treatment, an inverse correlation between the formation of 53BP1 foci and micronuclei generation was observed. The robust 53BP1 recruitment resulted in reduced micronuclei production. Thus, nanogold treatment stimulated an adaptive response in a human astrocyte cell. Jennifer Mytych, Anna Lewinska, Jacek Zebrowski, and Maciej Wnuk Copyright © 2015 Jennifer Mytych et al. All rights reserved. Dental Stem Cell Migration on Pulp Ceiling Cavities Filled with MTA, Dentin Chips, or Bio-Oss Wed, 03 Jun 2015 08:03:51 +0000 MTA, Bio-Oss, and dentin chips have been successfully used in endodontics. The aim of this study was to assess the adhesion and migration of dental stem cells on human pulp ceiling cavities filled with these endodontic materials in an experimental model, which mimics the clinical conditions of regenerative endodontics. Cavities were formed, by a homemade mold, on untouched third molars, filled with endodontic materials, and observed with electron microscopy. Cells were seeded on cavities’ surface and their morphology and number were analysed. The phenomenon of tropism was assessed in a migration assay. All three materials demonstrated appropriate microstructures for cell attachment. Cells grew on all reagents, but they showed a differential morphology. Moreover, variations were observed when comparing cells numbers on cavity’s filling versus the surrounding dentine disc. The highest number of cells was recorded on dentin chips whereas the opposite was true for Bio-Oss. This was confirmed in the migration assay where a statistically significant lower number of cells migrated towards Bio-Oss as compared to MTA and dentin chips. This study highlights that MTA and dentin chips have a greater potential compared to Bio-Oss regarding the attraction of dental stem cells and are good candidates for bioengineered pulp regeneration. Stefania Lymperi, Vasiliki Taraslia, Ioannis N. Tsatsoulis, Athina Samara, Athanasios D. Velentzas, Anastasia Agrafioti, Ema Anastasiadou, and Evangelos Kontakiotis Copyright © 2015 Stefania Lymperi et al. All rights reserved. A Novel Injectable Magnesium/Calcium Sulfate Hemihydrate Composite Cement for Bone Regeneration Sun, 31 May 2015 11:37:51 +0000 Objective. A novel injectable magnesium/calcium sulfate hemihydrate (Mg/CSH) composite with improved properties was reported here. Methods. Composition, setting time, injectability, compressive strength, and bioactivity in simulated body fluid (SBF) of the Mg/CSH composite were evaluated. Furthermore, the cellular responses of canine bone marrow stromal cells (cBMSCs) and bone formation capacity after the implantation of Mg/CSH in tibia defects of canine were investigated. Results. Mg/CSH possessed a prolonged setting time and markedly improved injectability and mechanical property . Mg/CSH samples showed better degradability than CSH in SBF after 21 days of soaking . Moreover, the degrees of cell attachment, proliferation, and capability of osteogenic differentiation on the Mg/CSH specimens were higher than those on CSH, without significant cytotoxicity and with the increased proliferation index, ALP activity, and expression levels of integrin β1 and Coll I in cBMSCs . Mg/CSH enhanced the efficiency of new bone formation at the tibia defect area, including the significantly elevated bone mineral density, bone area fraction, and Coll I expression level . Conclusions. The results implied that this new injectable bone scaffold exhibited promising prospects for bone repair and had a great potential in bone tissue engineering. Shanchuan Zhang, Ke Yang, Fuzhai Cui, Yi Jiang, Lingling E, Baohua Xu, and Hongchen Liu Copyright © 2015 Shanchuan Zhang et al. All rights reserved. The Use of Natural Polysaccharides as Biomaterials Mon, 25 May 2015 08:53:48 +0000 Paola Laurienzo, João C. Fernandes, Sylvia Colliec-Jouault, and J. Helen Fitton Copyright © 2015 Paola Laurienzo et al. All rights reserved. Prevention of Polyglycolic Acid-Induced Peritoneal Adhesions Using Alginate in a Rat Model Thu, 21 May 2015 14:18:05 +0000 Postoperative intra-abdominal or intrathoracic adhesions sometimes cause significant morbidity. We have designed three types of alginate-based treatments using strongly cross-linked (SL), weakly cross-linked (WL), and non-cross-linked (NL) alginate with calcium gluconate. In rat experiments, we compared the antiadhesive effects of the three types of alginate-based treatments, fibrin glue treatment (a standard treatment), and no treatment against adhesions caused by polyglycolic acid (PGA) mesh (PGA-induced adhesions). The antiadhesive materials were set on the PGA sheet fixed on the parietal peritoneum of the abdomen. Fifty-six days later, the adhesions were evaluated macroscopically by the adhesion scores and microscopically by hematoxylin-eosin staining and immunostaining. We also tested the fibroblast growth on the surface of the antiadhesive materials in vitro. The antiadhesive effects of WL and NL were superior to the no treatment and fibrin glue treatment. A microscopic evaluation confirmed that the PGA sheet was covered by a peritoneal layer constructed of well-differentiated mesothelial cells, and the inflammation was most improved in the NL and WL. The fibroblast growth was inhibited most on the surfaces of the NL and WL. These results suggest that either the WL or NL treatments are suitable for preventing PGA-induced adhesions compared to SL or the conventional treatment. Mari Matoba, Ayumi Hashimoto, Ayumi Tanzawa, Taichi Orikasa, Junki Ikeda, Yoshizumi Iwame, Yuki Ozamoto, Rie Abe, Hiroe Miyamoto, Chiko Yoshida, Toru Hashimoto, Hiroko Torii, Hideki Takamori, Shinichiro Morita, Hiroyuki Tsujimoto, and Akeo Hagiwara Copyright © 2015 Mari Matoba et al. All rights reserved. Insights in Behavior of Variably Formulated Alginate-Based Microcapsules for Cell Transplantation Wed, 20 May 2015 10:00:35 +0000 Alginate-based microencapsulation of live cells may offer the opportunity to treat chronic and degenerative disorders. So far, a thorough assessment of physical-chemical behavior of alginate-based microbeads remains cloudy. A disputed issue is which divalent cation to choose for a high performing alginate gelling process. Having selected, in our system, high mannuronic (M) enriched alginates, we studied different gelling cations and their combinations to determine their eventual influence on physical-chemical properties of the final microcapsules preparation, in vitro and in vivo. We have shown that used of ultrapure alginate allows for high biocompatibility of the formed microcapsules, regardless of gelation agents, while use of different gelling cations is associated with corresponding variable effects on the capsules’ basic architecture, as originally reported in this work. However, only the final application which the capsules are destined to will ultimately guide the selection of the ideal, specific gelling divalent cations, since in principle there are no capsules that are better than others. Pia Montanucci, Silvia Terenzi, Claudio Santi, Ilaria Pennoni, Vittorio Bini, Teresa Pescara, Giuseppe Basta, and Riccardo Calafiore Copyright © 2015 Pia Montanucci et al. All rights reserved. Preparation of Porous Chitosan-Siloxane Hybrids Coated with Hydroxyapatite Particles Wed, 20 May 2015 08:07:02 +0000 This paper describes the apatite deposition of chitosan-silicate porous hybrids derived from chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) in alkaline phosphate solution. The preparation of porous hybrids with needle-like apatite on their surfaces is described. Following apatite deposition the porous hybrids maintained high porosity. The enzymatic degradation rate was low even after 6 months and the porous hybrids were very flexible and cut easily using surgical scissors. Yuki Shirosaki, Kohei Okamoto, Satoshi Hayakawa, Akiyoshi Osaka, and Takuji Asano Copyright © 2015 Yuki Shirosaki et al. All rights reserved. Preliminary Study on Biosynthesis of Bacterial Nanocellulose Tubes in a Novel Double-Silicone-Tube Bioreactor for Potential Vascular Prosthesis Tue, 19 May 2015 14:30:38 +0000 Bacterial nanocellulose (BNC) has demonstrated a tempting prospect for applications in substitute of small blood vessels. However, present technology is inefficient in production and BNC tubes have a layered structure that may bring danger after implanting. Double oxygen-permeable silicone tubes in different diameters were therefore used as a tube-shape mold and also as oxygenated supports to construct a novel bioreactor for production of the tubular BNC materials. Double cannula technology was used to produce tubular BNC via cultivations with Acetobacter xylinum, and Kombucha, a symbiosis of acetic acid bacteria and yeasts. The results indicated that Kombucha gave higher yield and productivity of BNC than A. xylinum. Bacterial nanocellulose was simultaneously synthesized both on the inner surface of the outer silicone tube and on the outer surface of the inner silicone tube. Finally, the nano BNC fibrils from two directions formed a BNC tube with good structural integrity. Scanning electron microscopy inspection showed that the tubular BNC had a multilayer structure in the beginning but finally it disappeared and an intact BNC tube formed. The mechanical properties of BNC tubes were comparable with the reported value in literatures, demonstrating a great potential in vascular implants or in functional substitutes in biomedicine. Feng Hong, Bin Wei, and Lin Chen Copyright © 2015 Feng Hong et al. All rights reserved. Polysaccharide-Coated Magnetic Nanoparticles for Imaging and Gene Therapy Tue, 19 May 2015 13:59:23 +0000 Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Among the many different types of fabricated nanoparticles, magnetic metal oxide nanoparticles stand out as unique and useful tools for biomedical applications, because of their imaging characteristics and therapeutic properties such as drug and gene carriers. Polymer-coated magnetic particles are currently of particular interest to investigators in the fields of nanobiomedicine and fundamental biomaterials. Theranostic magnetic nanoparticles that are encapsulated or coated with polymers not only exhibit imaging properties in response to stimuli, but also can efficiently deliver various drugs and therapeutic genes. Even though a large number of polymer-coated magnetic nanoparticles have been fabricated over the last decade, most of these have only been used for imaging purposes. The focus of this review is on polysaccharide-coated magnetic nanoparticles used for imaging and gene delivery. Saji Uthaman, Sang Joon Lee, Kondareddy Cherukula, Chong-Su Cho, and In-Kyu Park Copyright © 2015 Saji Uthaman et al. All rights reserved. Recombinant Phage Coated 1D Al2O3 Nanostructures for Controlling the Adhesion and Proliferation of Endothelial Cells Tue, 19 May 2015 13:48:34 +0000 A novel synthesis of a nanostructured cell adhesive surface is investigated for future stent developments. One-dimensional (1D) Al2O3 nanostructures were prepared by chemical vapor deposition of a single source precursor. Afterwards, recombinant filamentous bacteriophages which display a short binding motif with a cell adhesive peptide (RGD) on p3 and p8 proteins were immobilized on these 1D Al2O3 nanostructures by a simple dip-coating process to study the cellular response of human endothelial EA hy.926. While the cell density decreased on as-deposited 1D Al2O3 nanostructures, we observed enhanced cell proliferation and cell-cell interaction on recombinant phage overcoated 1D Al2O3 nanostructures. The recombinant phage overcoating also supports an isotropic cell spreading rather than elongated cell morphology as we observed on as-deposited Al2O3 1D nanostructures. Juseok Lee, Hojeong Jeon, Ayman Haidar, Hashim Abdul-Khaliq, Michael Veith, Cenk Aktas, and Youngjun Kim Copyright © 2015 Juseok Lee et al. All rights reserved. A Direct Sulfation Process of a Marine Polysaccharide in Ionic Liquid Tue, 19 May 2015 13:43:45 +0000 GY785 is an exopolysaccharide produced by a mesophilic bacterial strain Alteromonas infernus discovered in the deep-sea hydrothermal vents. GY785 highly sulfated derivative (GY785 DRS) was previously demonstrated to be a promising molecule driving the efficient mesenchymal stem cell chondrogenesis for cartilage repair. This glycosaminoglycan- (GAG-) like compound was modified in a classical solvent (N,N′-dimethylformamide). However, the use of classical solvents limits the polysaccharide solubility and causes the backbone degradation. In the present study, a one-step efficient sulfation process devoid of side effects (e.g., polysaccharide depolymerization and/or degradation) was developed to produce GAG-like derivatives. The sulfation of GY785 derivative (GY785 DR) was carried out using ionic liquid as a reaction medium. The successful sulfation of this anionic and highly branched heteropolysaccharide performed in ionic liquid would facilitate the production of new molecules of high specificity for biological targets such as tissue engineering or regenerative medicine. Nathalie Chopin, Corinne Sinquin, Jacqueline Ratiskol, Agata Zykwinska, Pierre Weiss, Stéphane Cérantola, Jean Le Bideau, and Sylvia Colliec-Jouault Copyright © 2015 Nathalie Chopin et al. All rights reserved. Comparison and Characterisation of Regenerated Chitosan from 1-Butyl-3-methylimidazolium Chloride and Chitosan from Crab Shells Tue, 19 May 2015 13:37:27 +0000 Chitosan is a biopolymer derived from chitin which is naturally occurring in the exoskeleton of crustaceans. This paper reports dissolution and regeneration of chitosan by directly dissolving in an ionic liquid solvent, 1-butyl-3-methylimidazolium chloride (BMIMCl). This will provide an ideal platform to solubilise these kinds of polymers to achieve the dissolution. The current study dissolved chitosan from crab shell utilising BMIMCl as a solvent and characterised the resultant regenerated polymer. The regenerated chitosan showed increased hydrogen bonding when characterised by Fourier transform infrared (FTIR) spectral analysis. In addition, the study also compared the characteristics of regenerated and generic chitosan. The regenerated chitosan was also evaluated for antimicrobial properties and showed to possess antibacterial features similar to the commercial grade. This method can be utilised in future for blending of polymers with chitosan in a dissolved phase. Saniyat Islam, Lyndon Arnold, and Rajiv Padhye Copyright © 2015 Saniyat Islam et al. All rights reserved. 3D Bioprinting of Carboxymethylated-Periodate Oxidized Nanocellulose Constructs for Wound Dressing Applications Tue, 19 May 2015 13:35:35 +0000 Nanocellulose has a variety of advantages, which make the material most suitable for use in biomedical devices such as wound dressings. The material is strong, allows for production of transparent films, provides a moist wound healing environment, and can form elastic gels with bioresponsive characteristics. In this study, we explore the application of nanocellulose as a bioink for modifying film surfaces by a bioprinting process. Two different nanocelluloses were used, prepared with TEMPO mediated oxidation and a combination of carboxymethylation and periodate oxidation. The combination of carboxymethylation and periodate oxidation produced a homogeneous material with short nanofibrils, having widths <20 nm and lengths <200 nm. The small dimensions of the nanofibrils reduced the viscosity of the nanocellulose, thus yielding a material with good rheological properties for use as a bioink. The nanocellulose bioink was thus used for printing 3D porous structures, which is exemplified in this study. We also demonstrated that both nanocelluloses did not support bacterial growth, which is an interesting property of these novel materials. Adam Rees, Lydia C. Powell, Gary Chinga-Carrasco, David T. Gethin, Kristin Syverud, Katja E. Hill, and David W. Thomas Copyright © 2015 Adam Rees et al. All rights reserved. Hyaluronic Acid Based Hydrogels for Regenerative Medicine Applications Tue, 19 May 2015 12:45:39 +0000 Hyaluronic acid (HA) hydrogels, obtained by cross-linking HA molecules with divinyl sulfone (DVS) based on a simple, reproducible, and safe process that does not employ any organic solvents, were developed. Owing to an innovative preparation method the resulting homogeneous hydrogels do not contain any detectable residual cross-linking agent and are easier to inject through a fine needle. HA hydrogels were characterized in terms of degradation and biological properties, viscoelasticity, injectability, and network structural parameters. They exhibit a rheological behaviour typical of strong gels and show improved viscoelastic properties by increasing HA concentration and decreasing HA/DVS weight ratio. Furthermore, it was demonstrated that processes such as sterilization and extrusion through clinical needles do not imply significant alteration of viscoelastic properties. Both SANS and rheological tests indicated that the cross-links appear to compact the network, resulting in a reduction of the mesh size by increasing the cross-linker amount. In vitro degradation tests of the HA hydrogels demonstrated that these new hydrogels show a good stability against enzymatic degradation, which increases by increasing HA concentration and decreasing HA/DVS weight ratio. Finally, the hydrogels show a good biocompatibility confirmed by in vitro tests. Assunta Borzacchiello, Luisa Russo, Birgitte M. Malle, Khadija Schwach-Abdellaoui, and Luigi Ambrosio Copyright © 2015 Assunta Borzacchiello et al. All rights reserved. Preparation, Optimization, and Screening of the Effect of Processing Variables on Agar Nanospheres Loaded with Bupropion HCl by a D-Optimal Design Tue, 19 May 2015 12:39:39 +0000 Bupropion is an atypical antidepressant drug. Fluctuating in its serum levels following oral administration of immediate release dosage forms leads to occasional seizure. The aim of the present work was designing of sustained release bupropion HCl nanospheres suited for pulmonary delivery. Agar nanospheres were prepared by transferring the w/o emulsion to solid in oil (s/o) suspension. Calcium chloride was used as cross-linking agent and hydroxypropyl β-cyclodextrin (HPβCD) was used as permeability enhancer. A response surface D-optimal design was used for optimization of nanospheres. Independent factors included in the design were calcium chloride percent, speed of homogenization, agar percent, and HPβCD percent. Optimum condition was predicted to be achieved when the calcium chloride was set at 7.19%, homogenization speed at 8500 rpm, agar content at 2%, and HPβCD at 0.12%. The optimized nanoparticles showed particle size of 587 nm, zeta potential of −30.9 mV, drug loading efficiency of 38.6%, and release efficiency of 51% until 5 h. The nanospheres showed high degree of bioadhesiveness. D-optimal response surface method is a satisfactory design to optimize the fabrication of bupropion HCl loaded agar nanospheres and these nanospheres can be successively exploited to deliver bupropion in a controlled manner for a sufficiently extended period. Jaleh Varshosaz, Mohammad Reza Zaki, Mohsen Minaiyan, and Jaafar Banoozadeh Copyright © 2015 Jaleh Varshosaz et al. All rights reserved. Assessment of Atmospheric Pressure Plasma Treatment for Implant Osseointegration Tue, 19 May 2015 10:10:11 +0000 This study assessed the osseointegrative effects of atmospheric pressure plasma (APP) surface treatment for implants in a canine model. Control surfaces were untreated textured titanium (Ti) and calcium phosphate (CaP). Experimental surfaces were their 80-second air-based APP-treated counterparts. Physicochemical characterization was performed to assess topography, surface energy, and chemical composition. One implant from each control and experimental group (four in total) was placed in one radius of each of the seven male beagles for three weeks, and one implant from each group was placed in the contralateral radius for six weeks. After sacrifice, bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were assessed. X-ray photoelectron spectroscopy showed decreased surface levels of carbon and increased Ti and oxygen, and calcium and oxygen, posttreatment for Ti and CaP surfaces, respectively. There was a significant increase in BIC for APP-treated textured Ti surfaces at six weeks but not at three weeks or for CaP surfaces. There were no significant differences for BAFO between treated and untreated surfaces for either material at either time point. This suggests that air-based APP surface treatment may improve osseointegration of textured Ti surfaces but not CaP surfaces. Studies optimizing APP parameters and applications are warranted. Natalie R. Danna, Bryan G. Beutel, Nick Tovar, Lukasz Witek, Charles Marin, Estevam A. Bonfante, Rodrigo Granato, Marcelo Suzuki, and Paulo G. Coelho Copyright © 2015 Natalie R. Danna et al. All rights reserved. Antibacterial Effects and Biocompatibility of Titania Nanotubes with Octenidine Dihydrochloride/Poly(lactic-co-glycolic acid) Tue, 19 May 2015 09:52:35 +0000 Titanium (Ti) implants with long-term antibacterial ability and good biocompatibility are highly desirable materials that can be used to prevent implant-associated infections. In this study, titania nanotubes (TNTs) were synthesized on Ti surfaces through electrochemical anodization. Octenidine dihydrochloride (OCT)/poly(lactic-co-glycolic acid) (PLGA) was infiltrated into TNTs using a simple solvent-casting technique. OCT/PLGA-TNTs demonstrated sustained drug release and maintained the characteristic hollow structures of TNTs. TNTs (200 nm in diameter) alone exhibited slight antibacterial effect and good osteogenic activity but also evidently impaired adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). OCT/PLGA-TNTs (100 nm in diameter) supported BMSC adhesion and proliferation and showed good osteogenesis-inducing ability. OCT/PLGA-TNTs also exhibited good long-term antibacterial ability within the observation period of 7 d. The synthesized drug carrier with relatively long-term antibacterial ability and enhanced excellent biocompatibility demonstrated significant potential in bone implant applications. Zhiqiang Xu, Yingzhen Lai, Dong Wu, Wenxiu Huang, Sijia Huang, Lin Zhou, and Jiang Chen Copyright © 2015 Zhiqiang Xu et al. All rights reserved. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration Tue, 12 May 2015 09:02:38 +0000 Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes. Miguel Padial-Molina, Francisco O’Valle, Alejandro Lanis, Francisco Mesa, David M. Dohan Ehrenfest, Hom-Lay Wang, and Pablo Galindo-Moreno Copyright © 2015 Miguel Padial-Molina et al. All rights reserved. Biomechanical Stability of Dental Implants in Augmented Maxillary Sites: Results of a Randomized Clinical Study with Four Different Biomaterials and PRF and a Biological View on Guided Bone Regeneration Sun, 12 Apr 2015 11:49:48 +0000 Introduction. Bone regenerates mainly by periosteal and endosteal humoral and cellular activity, which is given only little concern in surgical techniques and choice of bone grafts for guided bone regeneration. This study investigates on a clinical level the biomechanical stability of augmented sites in maxillary bone when a new class of moldable, self-hardening calcium-phosphate biomaterials (SHB) is used with and without the addition of Platelet Rich Fibrin (aPRF) in the Piezotome-enhanced subperiosteal tunnel-technique (PeSPTT). Material and Methods. 82 patients with horizontal atrophy of anterior maxillary crest were treated with PeSPTT and randomly assigned biphasic (60% HA/40% bTCP) or monophasic (100% bTCP) SHB without or with addition of aPRF. 109 implants were inserted into the augmented sites after 8.3 months and the insertion-torque-value (ITV) measured as clinical expression of the (bio)mechanical stability of the augmented bone and compared to ITVs of a prior study in sinus lifting. Results. Significant better results of (bio)mechanical stability almost by two-fold, expressed by higher ITVs compared to native bone, were achieved with the used biomaterials and more constant results with the addition of aPRF. Conclusion. The use of SHB alone or combined with aPRF seems to be favourable to achieve a superior (bio)mechanical stable restored alveolar bone. Troedhan Angelo, Wainwright Marcel, Kurrek Andreas, and Schlichting Izabela Copyright © 2015 Troedhan Angelo et al. All rights reserved. Osteogenic Biomaterials in Contemporary Dentistry Wed, 08 Apr 2015 06:59:28 +0000 Seong-Hun Kim, Jae-Pyung Ahn, Homayoun H. Zadeh, and Eric J. W. Liou Copyright © 2015 Seong-Hun Kim et al. All rights reserved. An Alumina Toughened Zirconia Composite for Dental Implant Application: In Vivo Animal Results Mon, 06 Apr 2015 12:03:53 +0000 Ceramic materials are widely used for biomedical applications because of their remarkable biological and mechanical properties. Composites made of alumina and zirconia are particularly interesting owing to their higher toughness with respect to the monolithic materials. On this basis, the present study is focused on the in vivo behavior of alumina toughened zirconia (ATZ) dental implants treated with a hydrothermal process. A minipig model was implemented to assess the bone healing through histology and mRNA expression at different time points (8, 14, 28, and 56 days). The novel ATZ implant was compared to a titanium clinical standard. The implants were analyzed in terms of microstructure and surface roughness before in vivo tests. The most interesting result deals with a statistically significant higher digital histology index for ATZ implants with respect to titanium standard at 56 days, which is an unprecedented finding, to the authors’ knowledge. Even if further investigations are needed before proposing the clinical use in humans, the tested material proved to be a promising candidate among the possible ceramic dental implants. Gianmario Schierano, Federico Mussano, Maria Giulia Faga, Giulio Menicucci, Carlo Manzella, Cristian Sabione, Tullio Genova, Mitzy Mauthe von Degerfeld, Bruno Peirone, Adele Cassenti, Paola Cassoni, and Stefano Carossa Copyright © 2015 Gianmario Schierano et al. All rights reserved. Regulation of Osteoblast Differentiation by Acid-Etched and/or Grit-Blasted Titanium Substrate Topography Is Enhanced by 1,25(OH)2D3 in a Sex-Dependent Manner Mon, 06 Apr 2015 08:13:39 +0000 This study assessed contributions of micron-scale topography on clinically relevant titanium (Ti) to differentiation of osteoprogenitor cells and osteoblasts; the interaction of this effect with 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3); and if the effects are sex-dependent. Male and female rat bone marrow cells (BMCs) were cultured on acid-etched (A,  μm), grit-blasted (GB,  μm), or grit-blasted/acid-etched (SLA,  μm) Ti. BMCs were sensitive to surface topography and underwent osteoblast differentiation. This was greatest on SLA; acid etching and grit blasting contributed additively. Primary osteoblasts were also sensitive to SLA, with less effect from individual structural components, demonstrated by enhanced local factor production. Sex-dependent responses of BMCs to topography varied with parameter whereas male and female osteoblasts responded similarly to surface treatment. 1α,25(OH)2D3 enhanced cell responses on all surfaces similarly. Effects were sex-dependent and male cells grown on a complex microstructured surface were much more sensitive than female cells. These results indicate that effects of the complex SLA topography are greater than acid etching or grit blasting alone on multipotent BMCs and committed osteoblasts and that individual parameters are sex-specific. The effect of 1α,25(OH)2D3 was sex dependent. The results also suggest that levels of 1α,25(OH)2D3 in the patient may be important in osseointegration. Rene Olivares-Navarrete, Sharon L. Hyzy, Barbara D. Boyan, and Zvi Schwartz Copyright © 2015 Rene Olivares-Navarrete et al. All rights reserved. Optimizing Perfusion-Decellularization Methods of Porcine Livers for Clinical-Scale Whole-Organ Bioengineering Tue, 31 Mar 2015 06:37:14 +0000 Aim. To refine the decellularization protocol of whole porcine liver, which holds great promise for liver tissue engineering. Methods. Three decellularization methods for porcine livers (1% sodium dodecyl sulfate (SDS), 1% Triton X-100 + 1% sodium dodecyl sulfate, and 1% sodium deoxycholate + 1% sodium dodecyl sulfate) were studied. The obtained liver scaffolds were processed for histology, residual cellular content analysis, and extracellular matrix (ECM) components evaluation to investigate decellularization efficiency and ECM preservation. Rat primary hepatocytes were seeded into three kinds of scaffold to detect the biocompatibility. Results. The whole liver decellularization was successfully achieved following all three kinds of treatment. SDS combined with Triton had a high efficacy of cellular removal and caused minimal disruption of essential ECM components; it was also the most biocompatible procedure for primary hepatocytes. Conclusion. We have refined a novel, standardized, time-efficient, and reproducible protocol for the decellularization of whole liver which can be further adapted to liver tissue engineering. Qiong Wu, Ji Bao, Yong-jie Zhou, Yu-jia Wang, Zheng-gui Du, Yu-jun Shi, Li Li, and Hong Bu Copyright © 2015 Qiong Wu et al. All rights reserved. Advances in Gene Delivery Systems Mon, 30 Mar 2015 06:49:34 +0000 Surendra Nimesh, Sabina Halappanavar, Nagendra K. Kaushik, and Pradeep Kumar Copyright © 2015 Surendra Nimesh et al. All rights reserved. Delivery of Nucleic Acids and Nanomaterials by Cell-Penetrating Peptides: Opportunities and Challenges Thu, 26 Mar 2015 12:27:11 +0000 Many viral and nonviral systems have been developed to aid delivery of biologically active molecules into cells. Among these, cell-penetrating peptides (CPPs) have received increasing attention in the past two decades for biomedical applications. In this review, we focus on opportunities and challenges associated with CPP delivery of nucleic acids and nanomaterials. We first describe the nature of versatile CPPs and their interactions with various types of cargoes. We then discuss in vivo and in vitro delivery of nucleic acids and nanomaterials by CPPs. Studies on the mechanisms of cellular entry and limitations in the methods used are detailed. Yue-Wern Huang, Han-Jung Lee, Larry M. Tolliver, and Robert S. Aronstam Copyright © 2015 Yue-Wern Huang et al. All rights reserved. Biotribology in Knee Arthroplasty Thu, 26 Mar 2015 12:26:06 +0000 Thomas M. Grupp, Sandra Utzschneider, and Markus A. Wimmer Copyright © 2015 Thomas M. Grupp et al. All rights reserved. Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty Wed, 25 Mar 2015 09:15:31 +0000 The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected. Andrew J. Mitchelson, Craig J. Wilson, William M. Mihalko, Thomas M. Grupp, Blaine T. Manning, Douglas A. Dennis, Stuart B. Goodman, Tony H. Tzeng, Sonia Vasdev, and Khaled J. Saleh Copyright © 2015 Andrew J. Mitchelson et al. All rights reserved. Rapid Prototyping for In Vitro Knee Rig Investigations of Prosthetized Knee Biomechanics: Comparison with Cobalt-Chromium Alloy Implant Material Tue, 24 Mar 2015 06:33:49 +0000 Retropatellar complications after total knee arthroplasty (TKA) such as anterior knee pain and subluxations might be related to altered patellofemoral biomechanics, in particular to trochlear design and femorotibial joint positioning. A method was developed to test femorotibial and patellofemoral joint modifications separately with 3D-rapid prototyped components for in vitro tests, but material differences may further influence results. This pilot study aims at validating the use of prostheses made of photopolymerized rapid prototype material (RPM) by measuring the sliding friction with a ring-on-disc setup as well as knee kinematics and retropatellar pressure on a knee rig. Cobalt-chromium alloy (standard prosthesis material, SPM) prostheses served as validation standard. Friction coefficients between these materials and polytetrafluoroethylene (PTFE) were additionally tested as this latter material is commonly used to protect pressure sensors in experiments. No statistical differences were found between friction coefficients of both materials to PTFE. UHMWPE shows higher friction coefficient at low axial loads for RPM, a difference that disappears at higher load. No measurable statistical differences were found in knee kinematics and retropatellar pressure distribution. This suggests that using polymer prototypes may be a valid alternative to original components for in vitro TKA studies and future investigations on knee biomechanics. Christian Schröder, Arnd Steinbrück, Tatjana Müller, Matthias Woiczinski, Yan Chevalier, Patrick Weber, Peter E. Müller, and Volkmar Jansson Copyright © 2015 Christian Schröder et al. All rights reserved. Patients with Intolerance Reactions to Total Knee Replacement: Combined Assessment of Allergy Diagnostics, Periprosthetic Histology, and Peri-implant Cytokine Expression Pattern Thu, 19 Mar 2015 13:17:22 +0000 We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies. Peter Thomas, Christine von der Helm, Christoph Schopf, Farhad Mazoochian, Lars Frommelt, Hans Gollwitzer, Josef Schneider, Michael Flaig, Veit Krenn, Benjamin Thomas, and Burkhard Summer Copyright © 2015 Peter Thomas et al. All rights reserved. PMMA Third-Body Wear after Unicondylar Knee Arthroplasty Decuples the UHMWPE Wear Particle Generation In Vitro Thu, 19 Mar 2015 09:46:07 +0000 Introduction. Overlooked polymethylmethacrylate after unicondylar knee arthroplasty can be a potential problem, since this might influence the generated wear particle size and morphology. The aim of this study was the analysis of polyethylene wear in a knee wear simulator for changes in size, morphology, and particle number after the addition of third-bodies. Material and Methods. Fixed bearing unicondylar knee prostheses (UKA) were tested in a knee simulator for 5.0 million cycles. Following bone particles were added for 1.5 million cycles, followed by 1.5 million cycles with PMMA particles. A particle analysis by scanning electron microscopy of the lubricant after the cycles was performed. Size and morphology of the generated wear were characterized. Further, the number of particles per 1 million cycles was calculated for each group. Results. The particles of all groups were similar in size and shape. The number of particles in the PMMA group showed 10-fold higher values than in the bone and control group (PMMA: 12; bone: 12; control: 12). Conclusion. The addition of bone or PMMA particles in terms of a third-body wear results in no change of particle size and morphology. PMMA third-bodies generated tenfold elevated particle numbers. This could favor an early aseptic loosening. Alexander Christoph Paulus, Manja Franke, Michael Kraxenberger, Christian Schröder, Volkmar Jansson, and Sandra Utzschneider Copyright © 2015 Alexander Christoph Paulus et al. All rights reserved. Variability of TKR Knee Kinematics and Relationship with Gait Kinetics: Implications for Total Knee Wear Thu, 19 Mar 2015 08:28:18 +0000 Several factors, including compressive load and knee kinematics, have been shown to influence wear. External knee moments (a surrogate for load) have recently been correlated with the medial and lateral wear scar areas of an unconstrained, PCL retaining knee design. Therefore, the purpose of this study was to determine whether differences in kinetics during level walking are accompanied by specific differences in relative knee kinematics. Thirty TKR patients were gait tested using the point cluster technique to obtain 3D motions of the knee. External knee moments were calculated from ground reaction forces recorded with a multicomponent force plate. The subjects were separated into two distinct anteroposterior (AP) motion categories: a low motion group and a high motion group. Similarly, the low and high motion groups for internal-external (IE) rotation were also identified. For the IE motion, there was no significant difference between the transverse internal rotation moments between the two IE motion groups. However for the AP motion groups, a higher external peak flexion moment was found for the group displaying less AP motion. These observations suggest that subjects with higher joint moments execute smaller ranges of AP motion and thus are likely to incur less wear. Valentina Ngai and Markus A. Wimmer Copyright © 2015 Valentina Ngai and Markus A. Wimmer. All rights reserved. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury Tue, 03 Mar 2015 09:16:11 +0000 Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. Wei Zhang, Yuan Gao, Yan Zhou, Jianheng Liu, Licheng Zhang, Anhua Long, Lihai Zhang, and Peifu Tang Copyright © 2015 Wei Zhang et al. All rights reserved. Characterization of Bone Marrow Mononuclear Cells on Biomaterials for Bone Tissue Engineering In Vitro Mon, 23 Feb 2015 10:05:13 +0000 Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo. Dirk Henrich, René Verboket, Alexander Schaible, Kerstin Kontradowitz, Elsie Oppermann, Jan C. Brune, Christoph Nau, Simon Meier, Halvard Bonig, Ingo Marzi, and Caroline Seebach Copyright © 2015 Dirk Henrich et al. All rights reserved. Cellular Responses Evoked by Different Surface Characteristics of Intraosseous Titanium Implants Thu, 12 Feb 2015 12:24:36 +0000 The properties of biomaterials, including their surface microstructural topography and their surface chemistry or surface energy/wettability, affect cellular responses such as cell adhesion, proliferation, and migration. The nanotopography of moderately rough implant surfaces enhances the production of biological mediators in the peri-implant microenvironment with consequent recruitment of differentiating osteogenic cells to the implant surface and stimulates osteogenic maturation. Implant surfaces with moderately rough topography and with high surface energy promote osteogenesis, increase the ratio of bone-to-implant contact, and increase the bonding strength of the bone to the implant at the interface. Certain features of implant surface chemistry are also important in enhancing peri-implant bone wound healing. It is the purpose of this paper to review some of the more important features of titanium implant surfaces which have an impact on osseointegration. Liviu Feller, Yusuf Jadwat, Razia A. G. Khammissa, Robin Meyerov, Israel Schechter, and Johan Lemmer Copyright © 2015 Liviu Feller et al. All rights reserved. Gene Profiling of Bone around Orthodontic Mini-Implants by RNA-Sequencing Analysis Wed, 11 Feb 2015 12:21:21 +0000 This study aimed to evaluate the genes that were expressed in the healing bones around SLA-treated titanium orthodontic mini-implants in a beagle at early (1-week) and late (4-week) stages with RNA-sequencing (RNA-Seq). Samples from sites of surgical defects were used as controls. Total RNA was extracted from the tissue around the implants, and an RNA-Seq analysis was performed with Illumina TruSeq. In the 1-week group, genes in the gene ontology (GO) categories of cell growth and the extracellular matrix (ECM) were upregulated, while genes in the categories of the oxidation-reduction process, intermediate filaments, and structural molecule activity were downregulated. In the 4-week group, the genes upregulated included ECM binding, stem cell fate specification, and intramembranous ossification, while genes in the oxidation-reduction process category were downregulated. GO analysis revealed an upregulation of genes that were related to significant mechanisms, including those with roles in cell proliferation, the ECM, growth factors, and osteogenic-related pathways, which are associated with bone formation. From these results, implant-induced bone formation progressed considerably during the times examined in this study. The upregulation or downregulation of selected genes was confirmed with real-time reverse transcription polymerase chain reaction. The RNA-Seq strategy was useful for defining the biological responses to orthodontic mini-implants and identifying the specific genetic networks for targeted evaluations of successful peri-implant bone remodeling. Kyung-Yen Nahm, Jung Sun Heo, Jae-Hyung Lee, Dong-Yeol Lee, Kyu-Rhim Chung, Hyo-Won Ahn, and Seong-Hun Kim Copyright © 2015 Kyung-Yen Nahm et al. All rights reserved. Resistance to Fracture of Dental Roots Obturated with Different Materials Sun, 08 Feb 2015 08:54:44 +0000 The aim of this study was to compare the vertical fracture resistance of roots obturated with different root canal filling materials and sealers. Crowns of 55 extracted mandibular premolar teeth were removed to provide root lengths of 13 mm. Five roots were saved as negative control group (canals unprepared and unfilled). Fifty root canals were instrumented and then five roots were saved as positive control group (canals prepared but unfilled). The remaining 45 roots were randomly divided into three experimental groups ( root/group) and obturated with the following procedures: in group 1, glass ionomer-based sealer and cone (ActiV GP obturation system); in group 2, bioceramic sealer and cone (EndoSequence BC obturation system); and in group 3, roots were filled with bioceramic sealer and cone (Smartpaste bio obturation system). All specimens were tested in a universal testing machine for measuring fracture resistance. For each root, the force at the time of fracture was recorded in Newtons. The statistical analysis was performed by using Kruskal-Wallis and post hoc test. There were no significant differences between the three experimental groups. The fracture values of three experimental and negative control groups were significantly higher than the positive control group. Within the limitations of this study, all materials increased the fracture resistance of instrumented roots. Berkan Celikten, Ceren Feriha Uzuntas, and Kamran Gulsahi Copyright © 2015 Berkan Celikten et al. All rights reserved. The Osteogenic Properties of Multipotent Mesenchymal Stromal Cells in Cultures on TiO2 Sol-Gel-Derived Biomaterial Sun, 01 Feb 2015 13:22:16 +0000 The biocompatibility of the bone implants is a crucial factor determining the successful tissue regeneration. The aim of this work was to compare cellular behavior and osteogenic properties of rat adipose-derived multipotent stromal cells (ASCs) and bone marrow multipotent stromal cells (BMSCs) cultured on metallic substrate covered with TiO2 sol-gel-derived nanolayer. The morphology, proliferation rate, and osteogenic differentiation potential of both ASCs and BMSCs propagated on the biomaterials were examined. The potential for osteogenic differentiation of ASCs and BMSCs was determined based on the presence of specific markers of osteogenesis, that is, alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCL). Additionally, the concentration of calcium and phosphorus in extracellular matrix was determined using energy-dispersive X-ray spectroscopy (SEM-EDX). Obtained results showed that TiO2 layer influenced proliferation activity of ASCs, which manifested by shortening of population doubling time and increase of OPN secretion. However, characteristic features of cells morphology and growth pattern of cultures prompted us to conclude that ultrathin TiO2 layer might also enhance osteodifferentiation of BMSCs. Therefore in our opinion, both populations of MSCs should be used for biological evaluation of biomaterials compatibility, such results may enhance the area of investigations related to regenerative medicine. Krzysztof Marycz, Agnieszka Śmieszek, Jakub Grzesiak, Anna Siudzińska, Monika Marędziak, Anna Donesz-Sikorska, and Justyna Krzak Copyright © 2015 Krzysztof Marycz et al. All rights reserved. The Biocompatibility of Degradable Magnesium Interference Screws: An Experimental Study with Sheep Sat, 31 Jan 2015 10:06:19 +0000 Screws for ligament reconstruction are nowadays mostly made of poly-L-lactide (PLLA). However, magnesium-based biomaterials are gathering increased interest in this research field because of their good mechanical property and osteoanabolic influence on bone metabolism. The aim of this pilot study was to evaluate the biocompatibility of an interference screw for ligament reconstruction made of magnesium alloy W4 by diecasting and milling and using different PEO-coatings with calcium phosphates. PLLA and titanium screws were used as control samples. The screws were implanted in the femur condyle of the hind leg of a merino sheep. The observation period was six and twelve weeks and one year. Histomorphometric, immunohistochemical, immunofluorescence, and molecular biological evaluation were conducted. Further TEM analysis was done. In all magnesium screws a clinically relevant gas formation in the vicinity of the biomaterial was observed. Except for the PLLA and titanium control samples, no screw was fully integrated in the surrounding bone tissue. Regarding the fabrication process, milling seems to produce less gas liberation and has a better influence on bone metabolism than diecasting. Coating by PEO with calcium phosphates could not reduce the initial gas liberation but rather reduced the bone metabolism in the vicinity of the biomaterial. Ulrich Thormann, Volker Alt, Lydia Heimann, Cyrille Gasquere, Christian Heiss, Gabor Szalay, Jörg Franke, Reinhard Schnettler, and Katrin Susanne Lips Copyright © 2015 Ulrich Thormann et al. All rights reserved. Application of AMOR in Craniofacial Rabbit Bone Bioengineering Thu, 29 Jan 2015 12:15:47 +0000 Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans, preclinical studies will be necessary to demonstrate the feasibility of AMOR in progressively larger animal models. Marcelo Freire, Jeong-Ho Choi, Anthony Nguyen, Young Deok Chee, Joong-Ki Kook, Hyung-Keun You, and Homayoun H. Zadeh Copyright © 2015 Marcelo Freire et al. All rights reserved. Insight into Bone-Derived Biological Apatite: Ultrastructure and Effect of Thermal Treatment Wed, 28 Jan 2015 14:07:01 +0000 Objectives. This study aims at examining the ultrastructure of bone-derived biological apatite (BAp) from a series of small vertebrates and the effect of thermal treatment on its physiochemical properties. Materials and Methods. Femurs/fin rays and vertebral bodies of 5 kinds of small vertebrates were firstly analyzed with X-ray microtomography. Subsequently, BAp was obtained with thermal treatment and low power plasma ashing, respectively. The properties of BAp, including morphology, functional groups, and crystal characteristics were then analyzed. Results. The bones of grouper and hairtail were mainly composed of condensed bone. Spongy bone showed different distribution in the bones from frog, rat, and pigeon. No significant difference was found in bone mineral density of condensed bone and trabecular thickness of spongy bone. Only platelet-like crystals were observed for BAp obtained by plasma ashing, while rod-like and irregular crystals were both harvested from the bones treated by sintering. A much higher degree of crystallinity and larger crystal size but a lower content of carbonate were detected in the latter. Conclusion. Platelet-like BAp is the common inorganic component of vertebrate bones. BAp distributing in condensed and spongy bone may exhibit differing thermal reactivity. Thermal treatment may alter BAp’s in vivo structure and composition. Quan Liu, Haobo Pan, Zhuofan Chen, and Jukka Pekka Matinlinna Copyright © 2015 Quan Liu et al. All rights reserved. Prediction of Local Ultimate Strain and Toughness of Trabecular Bone Tissue by Raman Material Composition Analysis Wed, 28 Jan 2015 09:48:59 +0000 Clinical studies indicate that bone mineral density correlates with fracture risk at the population level but does not correlate with individual fracture risk well. Current research aims to better understand the failure mechanism of bone and to identify key determinants of bone quality, thus improving fracture risk prediction. To get a better understanding of bone strength, it is important to analyze tissue-level properties not influenced by macro- or microarchitectural factors. The aim of this pilot study was to identify whether and to what extent material properties are correlated with mechanical properties at the tissue level. The influence of macro- or microarchitectural factors was excluded by testing individual trabeculae. Previously reported data of mechanical parameters measured in single trabeculae under tension and bending and its compositional properties measured by Raman spectroscopy was evaluated. Linear and multivariate regressions show that bone matrix quality but not quantity was significantly and independently correlated with the tissue-level ultimate strain and postyield work . Principal component analysis extracted three independent components explaining 86% of the total variance, representing elastic, yield, and ultimate components according to the included mechanical parameters. Some matrix parameters were both included in the ultimate component, indicating that the variation in ultimate strain and postyield work could be largely explained by Raman-derived compositional parameters. Roberto Carretta, Edgar Stüssi, Ralph Müller, and Silvio Lorenzetti Copyright © 2015 Roberto Carretta et al. All rights reserved. Dragging Human Mesenchymal Stem Cells with the Aid of Supramolecular Assemblies of Single-Walled Carbon Nanotubes, Molecular Magnets, and Peptides in a Magnetic Field Mon, 26 Jan 2015 11:03:16 +0000 Human adipose-derived stem cells (hASCs) are an attractive cell source for therapeutic applicability in diverse fields for the repair and regeneration of damaged or malfunctioning tissues and organs. There is a growing number of cell therapies using stem cells due to their characteristics of modulation of immune system and reduction of acute rejection. So a challenge in stem cells therapy is the delivery of cells to the organ of interest, a specific site. The aim of this paper was to investigate the effects of a supramolecular assembly composed of single-walled carbon nanotubes (SWCNT), molecular magnets (lawsone-Co-phenanthroline), and a synthetic peptide (FWYANHYWFHNAFWYANHYWFHNA) in the hASCs cultures. The hASCs were isolated, characterized, expanded, and cultured with the SWCNT supramolecular assembly (SWCNT-MA). The assembly developed did not impair the cell characteristics, viability, or proliferation. During growth, the cells were strongly attached to the assembly and they could be dragged by an applied magnetic field of less than 0.3 T. These assemblies were narrower than their related allotropic forms, that is, multiwalled carbon nanotubes, and they could therefore be used to guide cells through thin blood capillaries within the human body. This strategy seems to be useful as noninvasive and nontoxic stem cells delivery/guidance and tracking during cell therapy. Ana Cláudia C. de Paula, Gustavo A. M. Sáfar, Alfredo M. Góes, Marcelo P. Bemquerer, Marcos A. Ribeiro, and Humberto O. Stumpf Copyright © 2015 Ana Cláudia C. de Paula et al. All rights reserved. Bone Regeneration of Hydroxyapatite/Alumina Bilayered Scaffold with 3 mm Passage-Like Medullary Canal in Canine Tibia Model Mon, 26 Jan 2015 06:40:44 +0000 The aim of this study was to evaluate the bone regeneration of hydroxyapatite (HA)/alumina bilayered scaffold with a 3 mm passage-like medullary canal in a beagle tibia model. A porous HA/alumina scaffold was fabricated using a polymeric template-coating technique. HA/alumina scaffold dimensions were 10 mm in outer diameter, 20 mm in length, and with either a 3 mm passage or no passage. A 20 mm segmental defect was induced using an oscillating saw through the diaphysis of the beagle tibia. The defects of six beagles were filled with HA/alumina bilayered scaffolds with a 3 mm passage or without. The segmental defect was fixated using one bone plate and six screws. Bone regeneration within the HA/alumina scaffolds was observed at eight weeks after implantation. The evaluation of bone regeneration within the scaffolds after implantation in a beagle tibia was performed using radiography, computerized tomography (CT), micro-CT, and fluorescence microscopy. New bone successfully formed in the tibia defects treated with 3 mm passage HA/alumina scaffolds compared to without-passage HA/alumina scaffolds. It was concluded that the HA/alumina bilayered scaffold with 3 mm passage-like medullary canal was instrumental in inducing host-scaffold engraftment of the defect as well as distributing the newly formed bone throughout the scaffold at 8 weeks after implantation. Jong Min Kim, Jun Sik Son, Seong Soo Kang, Gonhyung Kim, and Seok Hwa Choi Copyright © 2015 Jong Min Kim et al. All rights reserved. Nanoscale Bonding between Human Bone and Titanium Surfaces: Osseohybridization Thu, 15 Jan 2015 10:14:28 +0000 Until now, the chemical bonding between titanium and bone has been examined only through a few mechanical detachment tests. Therefore, in this study, a sandblasted and acid-etched titanium mini-implant was removed from a human patient after 2 months of placement in order to identify the chemical integration mechanism for nanoscale osseointegration of titanium implants. To prepare a transmission electron microscopy (TEM) specimen, the natural state was preserved as much as possible by cryofixation and scanning electron microscope/focused ion beam (SEM-FIB) milling without any chemical treatment. High-resolution TEM (HRTEM), energy dispersive X-ray spectroscopy (EDS), and scanning TEM (STEM)/electron energy loss spectroscopic analysis (EELS) were used to investigate the chemical composition and structure at the interface between the titanium and bone tissue. HRTEM and EDS data showed evidence of crystalline hydroxyapatite and intermixing of bone with the oxide layer of the implant. The STEM/EELS experiment provided particularly interesting results: carbon existed in polysaccharides, calcium and phosphorus existed as tricalcium phosphate (TCP), and titanium existed as oxidized titanium. In addition, the oxygen energy loss near edge structures (ELNESs) showed a possibility of the presence of CaTiO3. These STEM/EELS results can be explained by structures either with or without a chemical reaction layer. The possible existence of the osseohybridization area and the form of the carbon suggest that reconsideration of the standard definition of osseointegration is necessary. Jun-Sik Kim, Seok-Man Kang, Kyung-Won Seo, Kyung-Yen Nahm, Kyu-Rhim Chung, Seong-Hun Kim, and Jae-Pyeong Ahn Copyright © 2015 Jun-Sik Kim et al. All rights reserved. Increase in the Tibial Slope Reduces Wear after Medial Unicompartmental Fixed-Bearing Arthroplasty of the Knee Thu, 15 Jan 2015 08:07:42 +0000 Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of a medial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1:2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0°, 4°, and 8° (n = 3 in each group). Results. The wear rate decreased significantly between 0° and 4° slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8° did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g., the tension of the ligament) must also be considered. Patrick Weber, Christian Schröder, Jens Schwiesau, Sandra Utzschneider, Arnd Steinbrück, Matthias F. Pietschmann, Volkmar Jansson, and Peter E. Müller Copyright © 2015 Patrick Weber et al. All rights reserved. Acute and Chronic Local Inflammatory Reaction after Implantation of Different Extracellular Porcine Dermis Collagen Matrices in Rats Wed, 14 Jan 2015 13:54:32 +0000 Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX) were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells) were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like) macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like) macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material. Silke Lucke, Andreas Hoene, Uwe Walschus, Anette Kob, Jens-Wolfgang Pissarek, and Michael Schlosser Copyright © 2015 Silke Lucke et al. All rights reserved. CR TKA UHMWPE Wear Tested after Artificial Aging of the Vitamin E Treated Gliding Component by Simulating Daily Patient Activities Thu, 20 Nov 2014 10:06:53 +0000 The wear behaviour of total knee arthroplasty (TKA) is dominated by two wear mechanisms: the abrasive wear and the delamination of the gliding components, where the second is strongly linked to aging processes and stress concentration in the material. The addition of vitamin E to the bulk material is a potential way to reduce the aging processes. This study evaluates the wear behaviour and delamination susceptibility of the gliding components of a vitamin E blended, ultra-high molecular weight polyethylene (UHMWPE) cruciate retaining (CR) total knee arthroplasty. Daily activities such as level walking, ascending and descending stairs, bending of the knee, and sitting and rising from a chair were simulated with a data set received from an instrumented knee prosthesis. After 5 million test cycles no structural failure of the gliding components was observed. The wear rate was with  mg/million cycles falling within the limit of previous reports for established wear test methods. Jens Schwiesau, Bernhard Fritz, Ines Kutzner, Georg Bergmann, and Thomas M. Grupp Copyright © 2014 Jens Schwiesau et al. All rights reserved. Differences in Anatomy and Kinematics in Asian and Caucasian TKA Patients: Influence on Implant Positioning and Subsequent Loading Conditions in Mobile Bearing Knees Thu, 20 Nov 2014 09:58:28 +0000 The objective of our study was to determine the mechanical stress conditions under tibiofemoral loading with an overlay of knee kinematics in deep flexion on two different mobile bearing designs in comparison to in vivo failure modes. This study investigates the seldom but severe complication of fatigue failure of polyethylene components at mobile bearing total knee arthroplasty designs. Assuming a combination of a floor-based lifestyle and tibial malrotation as a possible reason for a higher failure rate in Asian countries we developed a simplified finite element model considering a tibiofemoral roll-back angle of 22° and the range of rotational motion of a clinically established floating platform design (e.motion FP) at a knee flexion angle of 120° in order to compare our results to failure modes found in retrieved implants. Compared to the failure mode observed in the clinical retrievals the locations of the occurring stress maxima as well as the tensile stress distribution show analogies. From our observations, we conclude that the newly introduced finite element model with an overlay of deep knee flexion (lateral roll-back) and considerable internally rotated tibia implant positioning is an appropriate analysis for knee design optimizations and a suitable method to predict clinical failure modes. Allan Maas, Tae Kyun Kim, Rolf K. Miehlke, Thomas Hagen, and Thomas M. Grupp Copyright © 2014 Allan Maas et al. All rights reserved. Influence of Orthotropy on Biomechanics of Peri-Implant Bone in Complete Mandible Model with Full Dentition Mon, 03 Nov 2014 14:01:07 +0000 Objective. The study was to investigate the impact of orthotropic material on the biomechanics of dental implant, based on a detailed mandible with high geometric and mechanical similarity. Materials and Methods. Multiple data sources were used to elaborate detailed biological structures and implant CAD models. In addition, an extended orthotropic material assignment methodology based on harmonic fields was used to handle the alveolar ridge region to generate compatible orthotropic fields. The influence of orthotropic material was compared with the commonly used isotropic model and simplified orthotropic model. Results. The simulation results showed that the values of stress and strain on the implant-bone interface almost increased in the orthotropic model compared to the isotropic case, especially for the cancellous bone. However, the local stress concentration was more obvious in the isotropic case compared to that in orthotropic case. The simple orthotropic model revealed irregular stress and strain distribution, compared to the isotropic model and the real orthotropic model. The influence of orthotropy was little on the implant, periodontal ligament, tooth enamel, and dentin. Conclusion. The orthotropic material has significant effect on stress and strain of implant-bone interface in the mandible, compared with the isotropic simulation. Real orthotropic mechanical properties of mandible should be emphasized in biomechanical studies of dental implants. Xi Ding, Sheng-Hui Liao, Xing-Hao Zhu, and Hui-Ming Wang Copyright © 2014 Xi Ding et al. All rights reserved. Elastin-Coated Biodegradable Photopolymer Scaffolds for Tissue Engineering Applications Thu, 23 Oct 2014 12:45:58 +0000 One of the main open issues in modern vascular surgery is the nonbiodegradability of implants used for stent interventions, which can lead to small caliber-related thrombosis and neointimal hyperplasia. Some new, resorbable polymeric materials have been proposed to substitute traditional stainless-steel stents, but so far they were affected by poor mechanical properties and low biocompatibility. In this respect, a new material, polypropylene fumarate (PPF), may be considered as a promising candidate to implement the development of next generation stents, due to its complete biodegradability, and excellent mechanical properties and the ease to be precisely patterned. Besides all these benefits, PPF has not been tested yet for vascular prosthesis, mainly because it proved to be almost inert, while the ability to elicit a specific biological function would be of paramount importance in such critical surgery applications. Here, we propose a biomimetic functionalization process, aimed at obtaining specific bioactivation and thus improved cell-polymer interaction. Porous PPF-based scaffolds produced by deep-UV photocuring were coated by elastin and the functionalized scaffolds were extensively characterized, revealing a stable bound between the protein and the polymer surface. Both 3T3 and HUVEC cell lines were used for in vitro tests displaying an enhancement of cells adhesion and proliferation on the functionalized scaffolds. Rossella Barenghi, Szabolcs Beke, Ilaria Romano, Paola Gavazzo, Balázs Farkas, Massimo Vassalli, Fernando Brandi, and Silvia Scaglione Copyright © 2014 Rossella Barenghi et al. All rights reserved. Surface Modifications of Dental Ceramic Implants with Different Glass Solder Matrices: In Vitro Analyses with Human Primary Osteoblasts and Epithelial Cells Sun, 14 Sep 2014 00:00:00 +0000 Ceramic materials show excellent esthetic behavior, along with an absence of hypersensitivity, making them a possible alternative implant material in dental surgery. However, their surface properties enable only limited osseointegration compared to titanium implants. Within this study, a novel surface coating technique for enhanced osseointegration was investigated biologically and mechanically. Specimens of tetragonal zirconia polycrystal (TZP) and aluminum toughened zirconia (ATZ) were modified with glass solder matrices in two configurations which mainly consisted of SiO2, Al2O3, K2O, and Na2O. The influence on human osteoblastic and epithelial cell viability was examined by means of a WST-1 assay as well as live/dead staining. A C1CP-ELISA was carried out to verify procollagen type I production. Uncoated/sandblasted ceramic specimens and sandblasted titanium surfaces were investigated as a reference. Furthermore, mechanical investigations of bilaterally coated pellets were conducted with respect to surface roughness and adhesive strength of the different coatings. These tests could demonstrate a mechanically stable implant coating with glass solder matrices. The coated ceramic specimens show enhanced osteoblastic and partly epithelial viability and matrix production compared to the titanium control. Hence, the new glass solder matrix coating could improve bone cell growth as a prerequisite for enhanced osseointegration of ceramic implants. Jana Markhoff, Enrico Mick, Aurica Mitrovic, Juliane Pasold, Katharina Wegner, and Rainer Bader Copyright © 2014 Jana Markhoff et al. All rights reserved. Can Pin-on-Disk Testing Be Used to Assess the Wear Performance of Retrieved UHMWPE Components for Total Joint Arthroplasty? Thu, 11 Sep 2014 08:19:13 +0000 The objective of this study was to assess the suitability of using multidirectional pin-on-disk (POD) testing to characterize wear behavior of retrieved ultrahigh molecular weight polyethylene (UHMWPE). The POD wear behavior of 25 UHMWPE components, retrieved after 10 years in vivo, was compared with 25 that were shelf aged for 10–15 years in their original packaging. Components were gamma sterilized (25–40 kGy) in an air or reduced oxygen (inert) package. 9 mm diameter pins were fabricated from each component and evaluated against CoCr disks using a super-CTPOD with 100 stations under physiologically relevant, multidirectional loading conditions. Bovine serum (20 g/L protein concentration) was used as lubricant. Volumetric wear rates were found to vary based on the aging environment, as well as sterilization environment. Volumetric wear rates were the lowest for the pins in the gamma inert, shelf aged cohort. These results support the utility of using modern, multidirectional POD testing with a physiologic lubricant as a novel method for evaluating wear properties of retrieved UHMWPE components. The data also supported the hypothesis that wear rates of gamma-inert liners were lower than gamma-air liners for both retrieved and shelf aging conditions. However, this difference was not statistically significant for the retrieved condition. Steven M. Kurtz, Daniel W. MacDonald, Sevi Kocagöz, Mariya Tohfafarosh, and Doruk Baykal Copyright © 2014 Steven M. Kurtz et al. All rights reserved. Effects of Soft Denture Liners on L929 Fibroblasts, HaCaT Keratinocytes, and RAW 264.7 Macrophages Thu, 11 Sep 2014 06:30:56 +0000 The effects of six soft liners (Ufi Gel P (UG), Sofreliner S (SR), Durabase Soft (D), Trusoft (T), Coe Comfort (CC), and Softone (ST)) on L929, HaCat, and RAW 264.7 cells were investigated. Eluates (24 and 48 h) from the materials were applied on the cells and the viability, type of cell death, and morphology were evaluated. Cells were also seeded on the specimens’ surfaces (direct contact) and incubated (24 or 48 h), and viability was analyzed. Controls were cells in culture medium without eluates or specimens. For cell viability, no significant differences were found among materials or between extraction periods, and the liners were noncytotoxic or slightly cytotoxic. Morphology of RAW 264.7 cells was altered by the 24 h eluates from CC and D and the 48 h eluates from SR, CC, and D. The 24 and 48 h eluates from all materials (except T) increased the percentages of L929 necrotic cells. For direct contact tests, the lowest cytotoxicity was observed for UG and SR. Although eluates did not reduce viability, morphology alterations and increase in necrosis were seen. Moreover, in the direct contact, effects on viability were more pronounced, particularly for D, T, CC and ST. Thus, the use of UG and SR might reduce the risk of adverse effects. Carolina de Andrade Lima Chaves, Carlos Alberto de Souza Costa, Carlos Eduardo Vergani, Pedro Paulo Chaves de Souza, and Ana Lucia Machado Copyright © 2014 Carolina de Andrade Lima Chaves et al. All rights reserved. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation Thu, 11 Sep 2014 00:00:00 +0000 Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4%) failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08) horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%), computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate. Alberto Monje, Michael A. Pikos, Hsun-Liang Chan, Fernando Suarez, Jordi Gargallo-Albiol, Federico Hernández-Alfaro, Pablo Galindo-Moreno, and Hom-Lay Wang Copyright © 2014 Alberto Monje et al. All rights reserved. Wear Behavior of an Unstable Knee: Stabilization via Implant Design? Tue, 09 Sep 2014 11:23:20 +0000 Background. Wear-related failures and instabilities are frequent failure mechanisms of total knee replacements. High-conforming designs may provide additional stability for the joint. This study analyzes the effects of a ligamentous insufficiency on the stability and the wear behavior of a high-conforming knee design. Methods. Two simulator wear tests were performed on a high-conforming total knee replacement design. In the first, a ligamentous-stable knee replacement with a sacrificed anterior cruciate ligament was simulated. In the second, a ligamentous-unstable knee with additionally insufficient posterior cruciate ligament and medial collateral ligament was simulated. Wear was determined gravimetrically and wear particles were analyzed. Implant kinematics was recorded during simulation. Results. Significantly higher wear rates () were observed for the unstable knee ( mg/106 cycles) compared to the stable knee ( mg/106 cycles). A higher number of wear particles with only small differences in wear particle characteristics were observed. Under unstable knee conditions, kinematics increased significantly for translations and rotations (). This increase was mainly attributed to higher tibial posterior translation and internal rotations. Conclusion. Higher kinematics under unstable test conditions is a result of insufficient stabilization via implant design. Due to the higher kinematics, increased wear was observed in this study. Jörn Reinders, Robert Sonntag, and Jan Philippe Kretzer Copyright © 2014 Jörn Reinders et al. All rights reserved. Periodontal Responses to Augmented Corticotomy with Collagen Membrane Application during Orthodontic Buccal Tipping in Dogs Tue, 09 Sep 2014 00:00:00 +0000 This prospective randomized split-mouth study was performed to examine the effects of absorbable collagen membrane (ACM) application in augmented corticotomy using deproteinized bovine bone mineral (DBBM), during orthodontic buccal tipping movement in the dog. After buccal circumscribing corticotomy and DBBM grafting into the decorticated area, flaps were repositioned and sutured on control sides. ACM was overlaid and secured with membrane tacks, on test sides only, and the flaps were repositioned and sutured. Closed coil springs were used to apply 200 g orthodontic force in the buccolingual direction on the second and third premolars, immediately after primary flap closure. The buccal tipping angles were ° and ° on the control and test sides, respectively. A mean of % of the buccal bone wall was replaced by new bone on the control side, and on the test side % was replaced. ACM application promoted an even bone surface. In conclusion, ACM application in augmented corticotomy using DBBM might stimulate periodontal tissue reestablishment, which is useful for rapid orthodontic treatment or guided bone regeneration. In particular, ACM could control the formation of mesenchymal matrix, facilitating an even bone surface. Dong-Yeol Lee, Hyo-Won Ahn, Yeek Herr, Young-Hyuk Kwon, Seong-Hun Kim, and Eun-Cheol Kim Copyright © 2014 Dong-Yeol Lee et al. All rights reserved. Clinical Evaluation of the Regenerative Potential of EMD and NanoHA in Periodontal Infrabony Defects: A 2-Year Follow-Up Mon, 08 Sep 2014 08:47:51 +0000 Introduction. The aim of this retrospective study was to compare the clinical efficacy of four different surgical techniques in promoting periodontal regeneration in patients with infrabony defects: open flap debridement, application of enamel matrix derivatives (EMD), nanohydroxyapatite (nanoHA) application, and combined nanoHA and EMD application. Probing attachment level (PAL), pocket depth (PD), and position of gingival margin at completion of therapy (REC) were measured. Materials and Methods. Data were collected from 64 healthy patients (34 women and 30 men, mean age 37,7 years). Clinical indices were measured by a calibrated examiner at baseline and at 12, 18, and 24 months. The values obtained for each treatment were compared using nonparametric tests. Results. All treatments resulted in a tendency toward PD reduction over time, with improvements in REC and PAL. The differences in PD, REC, and PAL values at baseline compared with values after 12, 18, and 24 months were statistically significant for all treatments. Statistically significant differences in PAL and PD were detected between nanoHA and nanoHA + EMD at 12, 18, and 24 months. Conclusion. In this study, EMD and nanoHA used together in patients with infrabony periodontal lesions had better clinical efficacy than nanoHA alone, EMD alone, or open flap debridement. Andrea Pilloni, Matteo Saccucci, Gabriele Di Carlo, Blerina Zeza, Marco Ambrosca, Michele Paolantonio, Gilberto Sammartino, Claudio Mongardini, and Antonella Polimeni Copyright © 2014 Andrea Pilloni et al. All rights reserved. Serum Metal Ion Concentrations in Paediatric Patients following Total Knee Arthroplasty Using Megaprostheses Mon, 08 Sep 2014 06:38:39 +0000 The purpose of this study was to determine the concentrations of cobalt, chromium, and molybdenum in the serum of paediatric tumour patients after fixed hinge total knee arthroplasty. Further, these metal ion levels were compared with serum metal ion levels of patients with other orthopaedic devices such as hip and knee prostheses with metal-on-metal or metal-on-polyethylene articulation to find differences between anatomical locations, abrasion characteristics, and bearing surfaces. After an average follow-up of 108 months (range: 67 to 163) of 11 paediatric patients with fixed hinge total knee arthroplasty, the mean concentrations for Co and Cr were significantly increased while Mo was within the limits compared to the upper values from the reference laboratory. Furthermore, these serum concentrations were significantly higher compared to patients with a standard rotating hinge device ( and ) and preoperative controls . On the other hand, the serum levels of patients following MoM THA or rotating hinge arthroplasty using megaprostheses were higher. Therefore, periodic long-term follow-ups are recommended due to the rising concerns about systemic metal ion exposure in the literature. Upon the occurrence of adverse reactions to metal debris the revision of the fixed hinge implant should be considered. Jörg Friesenbichler, Patrick Sadoghi, Werner Maurer-Ertl, Joanna Szkandera, Mathias Glehr, Kathrin Ogris, Matthias Wolf, Christian Weger, and Andreas Leithner Copyright © 2014 Jörg Friesenbichler et al. All rights reserved. Dynamic Contact Angle Analysis of Protein Adsorption on Polysaccharide Multilayer’s Films for Biomaterial Reendothelialization Mon, 08 Sep 2014 00:00:00 +0000 Atherosclerosis is a major cardiovascular disease. One of the side effects is restenosis. The aim of this work was to study the coating of stents by dextran derivates based polyelectrolyte’s multilayer (PEM) films in order to increase endothelialization of injured arterial wall after stent implantation. Films were composed with diethylaminoethyl dextran (DEAE) as polycation and dextran sulphate (DS) as polyanion. One film was composed with 4 bilayers of (DEAE-DS)4 and was labeled D−. The other film was the same as D− but with an added terminal layer of DEAE polycation: (DEAE-DS)4-DEAE (labeled D+). The dynamic adsorption/desorption of proteins on the films were characterized by dynamic contact angle (DCA) and atomic force microscopy (AFM). Human endothelial cell (HUVEC) adhesion and proliferation were quantified and correlated to protein adsorption analyzed by DCA for fibronectin, vitronectin, and bovine serum albumin (BSA). Our results showed that the endothelial cell response was optimal for films composed of DS as external layer. Fibronectin was found to be the only protein to exhibit a reversible change in conformation after desorption test. This behavior was only observed for (DEAE-DS)4 films. (DEAE-DS)4 films could enhance HUVEC proliferation in agreement with fibronectin ability to easily change from conformation. Safiya Benni, Thierry Avramoglou, Hanna Hlawaty, and Laurence Mora Copyright © 2014 Safiya Benni et al. All rights reserved. In Vitro Bioactivity and Antimicrobial Tuning of Bioactive Glass Nanoparticles Added with Neem (Azadirachta indica) Leaf Powder Sun, 07 Sep 2014 07:45:09 +0000 Silica and phosphate based bioactive glass nanoparticles (58SiO2-33CaO-9P2O5) with doping of neem (Azadirachta indica) leaf powder and silver nanoparticles were prepared and characterised. Bioactive glass nanoparticles were produced using sol-gel technique. In vitro bioactivity of the prepared samples was investigated using simulated body fluid. X-ray diffraction (XRD) pattern of prepared glass particles reveals amorphous phase and spherical morphology with a particle size of less than 50 nm. When compared to neem doped glass, better bioactivity was attained in silver doped glass through formation of hydroxyapatite layer on the surface, which was confirmed through XRD, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) analysis. However, neem leaf powder doped bioactive glass nanoparticles show good antimicrobial activity against Staphylococcus aureus and Escherichia coli and less bioactivity compared with silver doped glass particles. In addition, the biocompatibility of the prepared nanocomposites reveals better results for neem doped and silver doped glasses at lower concentration. Therefore, neem doped bioactive glass may act as a potent antimicrobial agent for preventing microbial infection in tissue engineering applications. M. Prabhu, S. Ruby Priscilla, K. Kavitha, P. Manivasakan, V. Rajendran, and P. Kulandaivelu Copyright © 2014 M. Prabhu et al. All rights reserved. Dynamics of Alloplastic Bone Grafts on an Early Stage of Corticotomy-Facilitated Orthodontic Tooth Movement in Beagle Dogs Wed, 03 Sep 2014 00:00:00 +0000 Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological findings, augmented corticotomy-facilitated orthodontic tooth movement might enhance the condition of the periodontal tissue and the stability of the outcomes of orthodontic treatment. Hyung-Joo Choi, Dong-Yeol Lee, and Tae-Woo Kim Copyright © 2014 Hyung-Joo Choi et al. All rights reserved. Systemic Treatment with Strontium Ranelate Accelerates the Filling of a Bone Defect and Improves the Material Level Properties of the Healing Bone Thu, 28 Aug 2014 00:00:00 +0000 Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.5 mm in diameter were created in 6-month-old female rats orally fed SrRan (625 mg/kg/d; 5/7 days) or vehicle for 4, 8, or 12 weeks (10 rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (µCT) and material level properties by nanoindentation analysis. µCT analysis showed that SrRan administration significantly improved microarchitecture of trabecular bone growing into the defect after 8 and 12 weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with different kinetics compared to trabecular bone, as the effects were already significant after 4 weeks. Nanoindentation analysis demonstrated that SrRan treatment significantly increased material level properties of both trabecular bone and cortical bone filling the defect compared to vehicle. SrRan accelerates the filling of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively. Giovanna Zacchetti, Romain Dayer, René Rizzoli, and Patrick Ammann Copyright © 2014 Giovanna Zacchetti et al. All rights reserved. Recent Trends of Polymer Mediated Liposomal Gene Delivery System Wed, 27 Aug 2014 12:12:01 +0000 Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD) blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole. Shyamal Kumar Kundu, Ashish Ranjan Sharma, Sang-Soo Lee, Garima Sharma, C. George Priya Doss, Shin Yagihara, Do-Young Kim, Ju-Suk Nam, and Chiranjib Chakraborty Copyright © 2014 Shyamal Kumar Kundu et al. All rights reserved. TolC Promotes ExPEC Biofilm Formation and Curli Production in Response to Medium Osmolarity Wed, 27 Aug 2014 09:19:58 +0000 While a high osmolarity medium activates Cpx signaling and causes CpxR to repress csgD expression, and efflux protein TolC protein plays an important role in biofilm formation in Escherichia coli, whether TolC also responds to an osmolarity change to regulate biofilm formation in extraintestinal pathogenic E. coli (ExPEC) remains unknown. In this study, we constructed ΔtolC mutant and complement ExPEC strains to investigate the role of TolC in the retention of biofilm formation and curli production capability under different osmotic conditions. The ΔtolC mutant showed significantly decreased biofilm formation and lost the ability to produce curli fimbriae compared to its parent ExPEC strain PPECC42 when cultured in M9 medium or 1/2 M9 medium of increased osmolarity with NaCl or sucrose at 28°C. However, biofilm formation and curli production levels were restored to wild-type levels in the ΔtolC mutant in 1/2 M9 medium. We propose for the first time that TolC protein is able to form biofilm even under high osmotic stress. Our findings reveal an interplay between the role of TolC in ExPEC biofilm formation and the osmolarity of the surrounding environment, thus providing guidance for the development of a treatment for ExPEC biofilm formation. Bo Hou, Xian-Rong Meng, Li-Yuan Zhang, Chen Tan, Hui Jin, Rui Zhou, Jian-Feng Gao, Bin Wu, Zi-Li Li, Mei Liu, Huan-Chun Chen, Ding-Ren Bi, and Shao-Wen Li Copyright © 2014 Bo Hou et al. All rights reserved. Adsorption of the Inflammatory Mediator High-Mobility Group Box 1 by Polymers with Different Charge and Porosity Wed, 27 Aug 2014 09:06:54 +0000 High-mobility group box 1 protein (HMGB1) is a conserved protein with a variety of biological functions inside as well as outside the cell. When released by activated immune cells, it acts as a proinflammatory cytokine. Its delayed release has sparked the interest in HMGB1 as a potential therapeutic target. Here, we studied the adsorption of HMGB1 to anionic methacrylate-based polymers as well as to neutral polystyrene-divinylbenzene copolymers. Both groups of adsorbents exhibited efficient binding of recombinant HMGB1 and of HMGB1 derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells. The adsorption characteristics depended on particle size, porosity, accessibility of the pores, and charge of the polymers. In addition to these physicochemical parameters of the adsorbents, modifications of the molecule itself (e.g., acetylation, phosphorylation, and oxidation), interaction with other plasma proteins or anticoagulants (e.g., heparin), or association with extracellular microvesicles may influence the binding of HMGB1 to adsorbents and lead to preferential depletion of HMGB1 subsets with different biological activity. Carla Tripisciano, Tanja Eichhorn, Stephan Harm, and Viktoria Weber Copyright © 2014 Carla Tripisciano et al. All rights reserved. Tooth Movement out of the Bony Wall Using Augmented Corticotomy with Nonautogenous Graft Materials for Bone Regeneration Wed, 27 Aug 2014 00:00:00 +0000 This prospective randomized split-mouth study was performed to compare the effects of augmented corticotomy with those of different nonautogenous bone graft materials combined with orthodontic tooth movement in dogs. Decortication was performed on the buccal bone surface of 6 male beagle dogs that were randomly assigned to receive grafts of deproteinized bovine bone mineral, irradiated cortical bone, or synthetic bone. Immediate orthodontic force was applied to the second and third premolars for buccal tipping for 6 weeks. The pocket depth and width of keratinized tissue (WKT) were measured. Histologic and histomorphometric analyses were performed. The probing depth, WKT, and ratio of the area of new bone to that of total bone on the buccal side were not significantly different between groups. All groups had considerable new bone formation on the pressure side. New bone formation on the buccal side and buccal plate formation in the coronal direction along the root surfaces were induced by the bone-derived and PDL-derived mesenchymal matrix, respectively. The angular change between groups was significantly different (P < 0.001). Augmented corticotomy using nonautogenous graft materials facilitated tooth movement without fenestrations and accelerated new bone formation on the pressure side. Kye-Bok Lee, Dong-Yeol Lee, Hyo-Won Ahn, Seong-Hun Kim, Eun-Cheol Kim, and Igor Roitman Copyright © 2014 Kye-Bok Lee et al. All rights reserved. Scaffolds Reinforced by Fibers or Tubes for Tissue Repair Mon, 18 Aug 2014 05:14:09 +0000 Xiaoming Li, Nicholas Dunne, Xiaowei Li, and Katerina E. Aifantis Copyright © 2014 Xiaoming Li et al. All rights reserved. Adhesion and Proliferation of Human Periodontal Ligament Cells on Poly(2-methoxyethyl acrylate) Wed, 06 Aug 2014 12:02:45 +0000 Human periodontal ligament (PDL) cells obtained from extracted teeth are a potential cell source for tissue engineering. We previously reported that poly(2-methoxyethyl acrylate) (PMEA) is highly biocompatible with human blood cells. In this study, we investigated the adhesion, morphology, and proliferation of PDL cells on PMEA and other types of polymers to design an appropriate scaffold for tissue engineering. PDL cells adhered and proliferated on all investigated polymer surfaces except for poly(2-hydroxyethyl methacrylate) and poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(n-butyl methacrylate)]. The initial adhesion of the PDL cells on PMEA was comparable with that on polyethylene terephthalate (PET). In addition, the PDL cells on PMEA spread well and exhibited proliferation behavior similar to that observed on PET. In contrast, platelets hardly adhered to PMEA. PMEA is therefore expected to be an excellent scaffold for tissue engineering and for culturing tissue-derived cells in a blood-rich environment. Erika Kitakami, Makiko Aoki, Chikako Sato, Hiroshi Ishihata, and Masaru Tanaka Copyright © 2014 Erika Kitakami et al. All rights reserved. Proteomics and Metabolomics for In Situ Monitoring of Wound Healing Mon, 04 Aug 2014 09:59:46 +0000 Wound healing of soft tissue and bone defects is a complex process in which cellular differentiation and adaption are regulated by internal and external factors, among them are many different proteins. In contrast to insights into the significance of various single proteins based on model systems, the knowledge about the processes at the actual site of wound healing is still limited. This is caused by a general lack of methods that allow sampling of extracellular factors, metabolites, and proteins in situ. Sampling of wound fluids in combination with proteomics and metabolomics is one of the promising approaches to gain comprehensive and time resolved data on effector molecules. Here, we describe an approach to sample metabolites by microdialysis and to extract proteins simultaneously by adsorption. With this approach it is possible (i) to collect, enrich, and purify proteins for a comprehensive proteome analysis; (ii) to detect more than 600 proteins in different defects including more than 100 secreted proteins, of which many proteins have previously been demonstrated to have diagnostic or predictive power for the wound healing state; and (iii) to combine continuous sampling of cytokines and metabolites and discontinuous sampling of larger proteins to gain complementary information of the same defect. Stefan Kalkhof, Yvonne Förster, Johannes Schmidt, Matthias C. Schulz, Sven Baumann, Anne Weißflog, Wenling Gao, Ute Hempel, Uwe Eckelt, Stefan Rammelt, and Martin von Bergen Copyright © 2014 Stefan Kalkhof et al. All rights reserved. Mercury and Other Biomedical Waste Management Practices among Dental Practitioners in India Mon, 04 Aug 2014 07:16:31 +0000 Objectives. The objective of the study was to assess the awareness and performance towards dental waste including mercury management policy and practices among the dental practitioners in North India. Materials and Methods. An epidemiologic survey was conducted among 200 private dental practitioners. The survey form was composed of 29 self-administered questions frame based on knowledge, attitude, and those regarding the practices of dentists in relation to dental health-care waste management. The resulting data were coded and a statistical analysis was done. Results and Discussion. About 63.7% of the dentists were not aware of the different categories of biomedical waste generated in their clinics. Only 31.9% of the dentists correctly said that outdated and contaminated drugs come under cytotoxic waste. 46.2% said they break the needle and dispose of it and only 21.9% use needle burner to destroy it. 45.0% of the dentists dispose of the developer and fixer solutions by letting them into the sewer, 49.4% of them dilute the solutions and let them into sewer and only 5.6% return them to the supplier. About 40.6% of the dentists dispose of excess silver amalgam by throwing it into common bin. Conclusion. It was concluded that not all dentists were aware of the risks they were exposed to and only half of them observe infection control practices. Raghuwar D. Singh, Sunit K. Jurel, Shuchi Tripathi, Kaushal K. Agrawal, and Reema Kumari Copyright © 2014 Raghuwar D. Singh et al. All rights reserved. Characterization of Morphology and Composition of Inorganic Fillers in Dental Alginates Thu, 24 Jul 2014 11:38:31 +0000 Energy dispersive X-ray spectroscopy microanalysis (EDX), scanning electron microscopy (SEM), and Archimedes’ Principle were used to determine the characteristics of inorganic filler particles in five dental alginates, including Cavex ColorChange (C), Hydrogum 5 (H5), Hydrogum (H), Orthoprint (O), and Jeltrate Plus (JP). The different alginate powders (0.5 mg) were fixed on plastic stubs and sputter coated with carbon for EDX analysis, then coated with gold, and observed using SEM. Volume fractions were determined by weighing a sample of each material in water before and after calcining at 450°C for 3 h. The alginate materials were mainly composed of silicon (Si) by weight (C—81.59%, H—79.89%, O—78.87%, H5—77.95%, JP—66.88%, wt). The filler fractions in volume (vt) were as follows: H5—84.85%, JP—74.76%, H—70.03%, O—68.31%, and C—56.10%. The tested materials demonstrated important differences in the inorganic elemental composition, filler fraction, and particle morphology. Ricardo Danil Guiraldo, Sandrine Bittencourt Berger, Rafael Leonardo Xediek Consani, Simonides Consani, Rodrigo Varella de Carvalho, Murilo Baena Lopes, Luciana Lira Meneghel, Fabiane Borges da Silva, and Mário Alexandre Coelho Sinhoreti Copyright © 2014 Ricardo Danil Guiraldo et al. All rights reserved. Cationic Polyene Phospholipids as DNA Carriers for Ocular Gene Therapy Thu, 24 Jul 2014 08:54:19 +0000 Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy. Susana Machado, Sofia Calado, Diogo Bitoque, Ana Vanessa Oliveira, Christer L. Øpstad, Muhammad Zeeshan, Hans-Richard Sliwka, Vassilia Partali, Michael D. Pungente, and Gabriela A. Silva Copyright © 2014 Susana Machado et al. All rights reserved. Immobilization of Murine Anti-BMP-2 Monoclonal Antibody on Various Biomaterials for Bone Tissue Engineering Wed, 23 Jul 2014 11:09:49 +0000 Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR. Sahar Ansari, Marcelo O. Freire, Eun-Kyoung Pang, Alaa I. Abdelhamid, Mohammad Almohaimeed, and Homayoun H. Zadeh Copyright © 2014 Sahar Ansari et al. All rights reserved. Modified Titanium Implant as a Gateway to the Human Body: The Implant Mediated Drug Delivery System Tue, 22 Jul 2014 11:25:44 +0000 The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases. Young-Seok Park, Joo-Youn Cho, Shin-Jae Lee, and Chee Il Hwang Copyright © 2014 Young-Seok Park et al. All rights reserved. Gene Delivery Potential of Biofunctional Carbonate Apatite Nanoparticles in Lungs Mon, 21 Jul 2014 07:07:57 +0000 Existing nonviral gene delivery systems to lungs are inefficient and associated with dose limiting toxicity in mammalian cells. Therefore, carbonate apatite (CO3Ap) nanoparticles were examined as an alternative strategy for effective gene delivery to the lungs. This study aimed to (1) assess the gene delivery efficiency of CO3Ap in vitro and in mouse lungs, (2) evaluate the cytotoxicity effect of CO3Ap/pDNA in vitro, and (3) characterize the CO3Ap/pDNA complex formulations. A significantly high level of reporter gene expression was detected from the lung cell line transfected with CO3Ap/pDNA complex prepared in both serum and serum-free medium. Cytotoxicity analysis revealed that the percentage of the viable cells treated with CO3Ap to be almost similar to the untreated cells. Characterization analyses showed that the CO3Ap/pDNA complexes are in a nanometer range with aggregated spherical structures and tended to be more negatively charged. In the lung of mice, highest level of transgene expression was observed when CO3Ap (8 μL) was complexed with 40 μg of pDNA at day 1 after administration. Although massive reduction of gene expression was seen beyond day 1 post administration, the level of expression remained significant throughout the study period. Suleiman Yusuf Alhaji, Ezharul Houque Chowdhury, Rozita Rosli, Fatma Hassan, and Syahril Abdullah Copyright © 2014 Suleiman Yusuf Alhaji et al. All rights reserved. Effect of Glass Fiber Incorporation on Flexural Properties of Experimental Composites Thu, 17 Jul 2014 08:41:53 +0000 This study evaluated the effect of fiber addiction in flexural properties of 30 wt% silica filled BisGMA resin (FR) or unfilled Bis-GMA (UR). Ten groups were created () varying the resin (FR or UR) and quantity of glass fibers (wt%: 0, 10, 15, 20, and 30). Samples (10 × 2 × 1 mm) were submitted to flexural strength test following SEM examination. Data were analyzed by two-way ANOVA, Tukey, and Student -test (). Results for flexural strength (MPa) were FR-groups: 0% , 10% , 15% , 20% , 30% ; UR-groups: 0% , 10% , 15% , 20% , and 30% , and for flexural modulus (GPa) FR-groups: 0% , 10% , 15% , 20% , and 30% ; UR-groups: 0% , 10% , 15% , 20% , and 30% . Fiber addiction in BisGMA resin increases flexural properties, and the interaction between resin and fibers seems better in the absence of inorganic fillers increasing flexural properties. Rodrigo Borges Fonseca, Aline Silva Marques, Karina de Oliveira Bernades, Hugo Lemes Carlo, and Lucas Zago Naves Copyright © 2014 Rodrigo Borges Fonseca et al. All rights reserved. Next Generation Delivery System for Proteins and Genes of Therapeutic Purpose: Why and How? Tue, 15 Jul 2014 00:00:00 +0000 Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. “Next generation delivery systems” may provide more efficient platform for delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation. Ashish Ranjan Sharma, Shyamal Kumar Kundu, Ju-Suk Nam, Garima Sharma, C. George Priya Doss, Sang-Soo Lee, and Chiranjib Chakraborty Copyright © 2014 Ashish Ranjan Sharma et al. All rights reserved. Antidiabetic Activity of Acacia tortilis (Forsk.) Hayne ssp. raddiana Polysaccharide on Streptozotocin-Nicotinamide Induced Diabetic Rats Wed, 09 Jul 2014 11:03:35 +0000 The present study was designed to investigate the antidiabetic activity of aqueous extract of Acacia tortilis polysaccharide (AEATP) from gum exudates and its role in comorbidities associated with diabetes in STZ-nicotinamide induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, glimepiride treated (10 mg/kg), and diabetic rats treated with 250, 500, and 1000 mg/kg dose of AEATP groups and fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, HDL, SGOT, and SGPT levels were measured. STZ significantly increased fasting blood glucose level, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels, whereas HDL level was reduced as compared to control group. After 7 days of administration, 500 and 1000 mg/kg dose of AEATP showed significant reduction in fasting blood glucose level compared to diabetic control. AEATP has also reduced total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels and improved HDL level as compared to diabetic control group. Our study is the first to report the normalization of fasting blood glucose level, lipid profile, and liver enzyme in AEATP treated diabetic rats. Thus, it can be concluded that AEATP may have potentials for the treatment of T2DM and its comorbidities. Pradeep Kumar Bhateja and Randhir Singh Copyright © 2014 Pradeep Kumar Bhateja and Randhir Singh. All rights reserved. Physicochemical Characteristics of Bone Substitutes Used in Oral Surgery in Comparison to Autogenous Bone Tue, 08 Jul 2014 08:17:17 +0000 Bone substitutes used in oral surgery include allografts, xenografts, and synthetic materials that are frequently used to compensate bone loss or to reinforce repaired bone, but little is currently known about their physicochemical characteristics. The aim of this study was to evaluate a number of physical and chemical properties in a variety of granulated mineral-based biomaterials used in dentistry and to compare them with those of autogenous bone. Autogenous bone and eight commercial biomaterials of human, bovine, and synthetic origins were studied by high-resolution X-ray diffraction, atomic absorption spectrometry, and laser diffraction to determine their chemical composition, calcium release concentration, crystallinity, and granulation size. The highest calcium release concentration was 24. 94 mg/g for Puros and the lowest one was 2.83 mg/g for Ingenios β-TCP compared to 20.15 mg/g for natural bone. The range of particles sizes, in terms of median size D50, varied between 1.32 μm for BioOss and 902.41 μm for OsteoSponge, compared to 282.1 μm for natural bone. All samples displayed a similar hexagonal shape as bone, except Ingenios β-TCP, Macrobone, and OsteoSponge, which showed rhomboid and triclinic shapes, respectively. Commercial bone substitutes significantly differ in terms of calcium concentration, particle size, and crystallinity, which may affect their in vivo performance. Antoine Berberi, Antoine Samarani, Nabih Nader, Ziad Noujeim, Maroun Dagher, Wasfi Kanj, Rita Mearawi, Ziad Salemeh, and Bassam Badran Copyright © 2014 Antoine Berberi et al. All rights reserved. Development of New Method for Simultaneous Analysis of Piracetam and Levetiracetam in Pharmaceuticals and Biological Fluids: Application in Stability Studies Tue, 08 Jul 2014 06:33:50 +0000 RP-HPLC ultraviolet detection simultaneous quantification of piracetam and levetiracetam has been developed and validated. The chromatography was obtained on a Nucleosil C18 column of , 10 m, dimension. The mobile phase was a (70 : 30 v/v) mixture of 0.1 g/L of triethylamine and acetonitrile. Smooth flow of mobile phase at 1 mL/min was set and 205 nm wavelength was selected. Results were evaluated through statistical parameters which qualify the method reproducibility and selectivity for the quantification of piracetam, levetiracetam, and their impurities hence proving stability-indicating properties. The proposed method is significantly important, permitting the separation of the main constituent piracetam from levetiracetam. Linear behavior was observed between 20 ng/mL and 10000 ng/mL for both drugs. The proposed method was checked in bulk drugs, dosage formulations, physiological condition, and clinical investigations and excellent outcome was witnessed. Farhan Ahmed Siddiqui, Nawab Sher, Nighat Shafi, Alisha Wafa Sial, Mansoor Ahmad, Mehjebeen, and Huma Naseem Copyright © 2014 Farhan Ahmed Siddiqui et al. All rights reserved. Influence of Thread Pitch, Helix Angle, and Compactness on Micromotion of Immediately Loaded Implants in Three Types of Bone Quality: A Three-Dimensional Finite Element Analysis Tue, 08 Jul 2014 00:00:00 +0000 This study investigated the influence of thread pitch, helix angle, and compactness on micromotion in immediately loaded implants in bone of varying density (D2, D3, and D4). Five models of the three-dimensional finite element (0.8 mm pitch, 1.6 mm pitch, 2.4 mm pitch, double-threaded, and triple-threaded implants) in three types of bone were created using Pro/E, Hypermesh, and ABAQUS software. The study had three groups: Group 1, different pitches (Pitch Group); Group 2, same compactness but different helix angles (Angle Group); and Group 3, same helix angle but different compactness (Compact Group). Implant micromotion was assessed as the comprehensive relative displacement. We found that vertical relative displacement was affected by thread pitch, helix angle, and compactness. Under vertical loading, displacement was positively correlated with thread pitch and helix angle but negatively with compactness. Under horizontal loading in D2, the influence of pitch, helix angle, and compactness on implant stability was limited; however, in D3 and D4, the influence of pitch, helix angle, and compactness on implant stability is increased. The additional evidence was provided that trabecular bone density has less effect on implant micromotion than cortical bone thickness. Bone type amplifies the influence of thread pattern on displacement. Pan Ma, Wei Xiong, Baosheng Tan, Wei Geng, Jiaqiang Liu, Weihong Li, and Dehua Li Copyright © 2014 Pan Ma et al. All rights reserved. Development and Characterization of Novel Porous 3D Alginate-Cockle Shell Powder Nanobiocomposite Bone Scaffold Mon, 07 Jul 2014 12:20:01 +0000 A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano cockle shell powder/nCP) through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects. B. Hemabarathy Bharatham, Md. Zuki Abu Bakar, Enoch Kumar Perimal, Loqman Mohamed Yusof, and Muhajir Hamid Copyright © 2014 B. Hemabarathy Bharatham et al. All rights reserved. Biomaterials: Chitosan and Collagen for Regenerative Medicine Tue, 01 Jul 2014 08:47:24 +0000 Yoshihiko Hayashi, Mitsuo Yamauchi, Se-Kwon Kim, and Hideo Kusaoke Copyright © 2014 Yoshihiko Hayashi et al. All rights reserved. Initial Sliding Wear Kinetics of Two Types of Glass Ionomer Cement: A Tribological Study Sun, 29 Jun 2014 11:34:38 +0000 The aim of this work was to characterize the initial wear kinetics of two different types of glass ionomer cement used in dentistry (the conventional glass ionomer cement and the resin-modified glass ionomer cement) under sliding friction after 28-day storing in distilled water or Ringer’s solution. Sliding friction was applied through a pin-on-disk tribometer, in sphere-on-plane contact conditions, under 5 N normal load and 120 rotations per minute. The test lasted 7500 cycles and replicas were performed at 2500, 5000 and 7500 cycles. A profilometer was used to evaluate the wear volume. Data were analysed using Student’s -test at a significant level of 5%. There is no statistical significant difference between the results obtained for a given material with the maturation media (). However, for a given maturation medium, there are significant statistical differences between the data obtained for the two materials at each measurement (). The wear rates of both materials decrease continuously during the running-in period between 0 and 2500 cycles. After 2500 cycles, the wear rate becomes constant and equal for both materials. The resin matrix contained in the resin-modified glass ionomer cement weakens the tribological behaviour of this material. Cyril Villat, Pierre Ponthiaux, Nelly Pradelle-Plasse, Brigitte Grosgogeat, and Pierre Colon Copyright © 2014 Cyril Villat et al. All rights reserved. Biological Assessment of a Calcium Silicate Incorporated Hydroxyapatite-Gelatin Nanocomposite: A Comparison to Decellularized Bone Matrix Thu, 26 Jun 2014 09:22:06 +0000 Our laboratory utilized biomimicry to develop a synthetic bone scaffold based on hydroxyapatite-gelatin-calcium silicate (HGCS). Here, we evaluated the potential of HGCS scaffold in bone formation in vivo using the rat calvarial critical-sized defect (CSD). Twelve Sprague-Dawley rats were randomized to four groups: control (defect only), decellularized bone matrix (DECBM), and HGCS with and without multipotent adult progenitor cells (MAPCs). DECBM was prepared by removing all the cells using SDS and NH4OH. After 12 weeks, the CSD specimens were harvested to evaluate radiographical, histological, and histomorphometrical outcomes. The in vitro osteogenic effects of the materials were studied by focal adhesion, MTS, and alizarin red. Micro-CT analysis indicated that the DECBM and the HGCS scaffold groups developed greater radiopaque areas than the other groups. Bone regeneration, assessed using histological analysis and fluorochrome labeling, was the highest in the HGCS scaffold seeded with MAPCs. The DECBM group showed limited osteoinductivity, causing a gap between the implant and host tissue. The group grafted with HGCS+MAPCs resulting in twice as much new bone formation seems to indicate a role for effective bone regeneration. In conclusion, the novel HGCS scaffold could improve bone regeneration and is a promising carrier for stem cell-mediated bone regeneration. Dong Joon Lee, Ricardo Padilla, He Zhang, Wei-Shou Hu, and Ching-Chang Ko Copyright © 2014 Dong Joon Lee et al. All rights reserved. Early Results of a New Rotating Hinge Knee Implant Wed, 25 Jun 2014 12:19:24 +0000 Background. Indication for rotating hinge (RH) total knee arthroplasty (TKA) includes primary and revision cases, with contradictory results. The aim of this study was to report prospective early results of a new modular rotating hinge TKA (EnduRo). For this implant several new design features and a new bearing material (carbon-fiber reinforced poly-ether-ether-ketone) have been developed. Furthermore, we tried to establish a new classification of failure modes for revision TKA. Methods. 152 EnduRo rotating-hinge prostheses were implanted in two centers. In 90 patients a primary implantation has been performed and 62 patients were revision cases. Knee Society Score (KSS), Western Ontario and McMaster Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), and Range of motion (ROM) were assessed before surgery, 3 months postoperatively, 12 months postoperatively, and annually thereafter. We defined 3 types of complications: Type 1, infection; type 2, periprosthetic complications; type 3, implant failures. Results. KSS, WOMAC, OKS, and ROM revealed significant improvements between the preoperative and the follow-up investigations. There were 14 complications (9.2%) leading to revision surgery, predominantly type 2. Conclusion. Our study shows excellent clinical results of the EnduRo TKA. Furthermore, no premature material failure or unusual biological response to the new bearing material could be detected. Alexander Giurea, Hans-Joachim Neuhaus, Rolf Miehlke, Reinhard Schuh, Richard Lass, Bernd Kubista, and Reinhard Windhager Copyright © 2014 Alexander Giurea et al. All rights reserved. Differential Expression of Osteo-Modulatory Molecules in Periodontal Ligament Stem Cells in Response to Modified Titanium Surfaces Wed, 25 Jun 2014 07:36:37 +0000 This study assessed differential gene expression of signaling molecules involved in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) subjected to different titanium (Ti) surface types. PDLSCs were cultured on tissue culture polystyrene (TCPS), and four types of Ti discs (PT, SLA, hydrophilic PT (pmodPT), and hydrophilic SLA (modSLA)) with no osteoinductive factor and then osteogenic activity, including alkaline phosphatase (ALP) activity, mRNA expression of runt-related gene 2, osterix, FOSB, FRA1, and protein levels of osteopontin and collagen type IA, were examined. The highest osteogenic activity appeared in PDLSCs cultured on SLA, compared with the TCPS and other Ti surfaces. The role of surface properties in affecting signaling molecules to modulate PDLSC behavior was determined by examining the regulation of Wnt pathways. mRNA expression of the canonical Wnt signaling molecules, Wnt3a and β-catenin, was higher on SLA and modSLA than on smooth surfaces, but gene expression of the calcium-dependent Wnt signaling molecules Wnt5a, calmodulin, and NFATc1 was increased significantly on PT and pmodPT. Moreover, integrin α2/β1, sonic hedgehog, and Notch signaling molecules were affected differently by each surface modification. In conclusion, surface roughness and hydrophilicity can affect differential Wnt pathways and signaling molecules, targeting the osteogenic differentiation of PDLSCs. So Yeon Kim, Ji-Yeon Yoo, Joo-Young Ohe, Jung-Woo Lee, Ji-Hoi Moon, Yong-Dae Kwon, and Jung Sun Heo Copyright © 2014 So Yeon Kim et al. All rights reserved. Development and Characterization of In Situ Oral Gel of Spiramycin Tue, 24 Jun 2014 00:00:00 +0000 The present investigation deals with the optimization, formulation, and characterization of oral in situ gel of spiramycin. Sodium alginate and hydroxypropyl methylcellulose were used as cross-linking and viscosifying agents, respectively. Sodium bicarbonate was used as a floating agent. In preformulation studies, the melting point, pH, and partition coefficient were found to be 133°C, 9.5, and 0.193, respectively. The drug had retention time at around 2.65 minutes in high performance liquid chromatography (HPLC). During compatibility studies of drug with all polymers, we observed that there were no changes in the FTIR spectra of a mixture of drug and polymers. All the formulations showed good pourability. Floating time and total floating time were 30 sec and >12 hours, respectively. During in vitro drug release studies, the drug was released from the formulation around 80–100% for 12–16 hrs. In TEM analysis, we found that the drug molecules were well entrapped in the polymer and the drug was released slowly for up to 12 hrs. In these studies, we found that the concentration of sodium alginate and HPMC had significant influence on floating lag time, gelling capacity, and cumulative percentage drug release. During antimicrobial studies, we found that the formulation containing spiramycin showed good zone of inhibition against different microbial strains (Staphylococcus aureus and Escherichia coli). Avinash Sharma, Jyoti Sharma, Rupinder Kaur, and Vinay Saini Copyright © 2014 Avinash Sharma et al. All rights reserved. Biological Width around One- and Two-Piece Implants Retrieved from Human Jaws Mon, 23 Jun 2014 08:20:20 +0000 Several histologic studies regarding peri-implant soft tissues and biological width around dental implants have been done in animals. However, these findings in human peri-implant soft tissues are very scarce. Therefore, the aim of this case series was to compare the biological width around unloaded one- and two-piece implants retrieved from human jaws. Eight partially edentulous patients received 2 test implants in the posterior mandible: one-piece (solid implants that comprise implant and abutment in one piece) and two-piece (external hexagon with a healing abutment) implants. After 4 months of healing, the implants and surrounding tissue were removed for histologic analysis. The retrieved implants showed healthy peri-implant bone and exhibited early stages of maturation. Marginal bone loss, gaps, and fibrous tissue were not present around retrieved specimens. The biologic width dimension ranged between 2.55 ± 0.16 and 3.26 ± 0.15 to one- and two-piece implants, respectively (). This difference was influenced by the connective tissue attachment, while sulcus depth and epithelial junction presented the same dimension for both groups (). Within the limits of this study, it could be shown that two-piece implants resulted in the thickening of the connective tissue attachment, resulting in the increase of the biological width, when compared to one-piece implants. Ricardo Judgar, Gabriela Giro, Elton Zenobio, Paulo G. Coelho, Magda Feres, Jose A. Rodrigues, Carlo Mangano, Giovanna Iezzi, Adriano Piattelli, and Jamil Awad Shibli Copyright © 2014 Ricardo Judgar et al. All rights reserved. Osteoblast-Like Cell Behavior on Porous Scaffolds Based on Poly(styrene) Fibers Thu, 19 Jun 2014 11:02:22 +0000 Scaffolds of nonresorbable biomaterials can represent an interesting alternative for replacing large bone defects in some particular clinical cases with massive bone loss. Poly(styrene) microfibers were prepared by a dry spinning method. They were partially melted to provide 3D porous scaffolds. The quality of the material was assessed by Raman spectroscopy. Surface roughness was determined by atomic force microscopy and vertical interference microscopy. Saos-2 osteoblast-like cells were seeded on the surface of the fibers and left to proliferate. Cell morphology, evaluated by scanning electron microscopy, revealed that they can spread and elongate on the rough microfiber surface. Porous 3D scaffolds made of nonresorbable poly(styrene) fibers are cytocompatible biomaterials mimicking allogenic bone trabeculae and allowing the growth and development of osteoblast-like cells in vitro. Andrada Serafim, Romain Mallet, Florence Pascaretti-Grizon, Izabela-Cristina Stancu, and Daniel Chappard Copyright © 2014 Andrada Serafim et al. All rights reserved. Vegetable Oil Derived Solvent, and Catalyst Free “Click Chemistry” Thermoplastic Polytriazoles Tue, 17 Jun 2014 08:01:13 +0000 Azide-alkyne Huisgen “click” chemistry provides new synthetic routes for making thermoplastic polytriazole polymers—without solvent or catalyst. This method was used to polymerize three diester dialkyne monomers with a lipid derived 18 carbon diazide to produce a series of polymers (labelled C18C18, C18C9, and C18C4 based on monomer chain lengths) free of residual solvent and catalyst. Three diester dialkyne monomers were synthesized with ester chain lengths of 4, 9, and 18 carbons from renewable sources. Significant differences in thermal and mechanical properties were observed between C18C9 and the two other polymers. C18C9 presented a lower melting temperature, higher elongation at break, and reduced Young’s modulus compared to C18C4 and C18C18. This was due to the “odd-even” effect induced by the number of carbon atoms in the monomers which resulted in orientation of the ester linkages of C18C9 in the same direction, thereby reducing hydrogen bonding. The thermoplastic polytriazoles presented are novel polymers derived from vegetable oil with favourable mechanical and thermal properties suitable for a large range of applications where no residual solvent or catalyst can be tolerated. Their added potential biocompatibility and biodegradability make them ideal for applications in the medical and pharmaceutical industries. Michael C. Floros, Alcides Lopes Leão, and Suresh S. Narine Copyright © 2014 Michael C. Floros et al. All rights reserved. A Review on Biodentine, a Contemporary Dentine Replacement and Repair Material Mon, 16 Jun 2014 00:00:00 +0000 Biodentine is a calcium-silicate based material that has drawn attention in recent years and has been advocated to be used in various clinical applications, such as root perforations, apexification, resorptions, retrograde fillings, pulp capping procedures, and dentine replacement. There has been considerable research performed on this material since its launching; however, there is scarce number of review articles that collates information and data obtained from these studies. Therefore, this review article was prepared to provide the reader with a general picture regarding the findings about various characteristics of the material. The results of a PubMed search were classified and presented along with some critical comments where necessary. The review initially focuses on various physical properties of the material with subheadings and continues with biocompatibility. Another section includes the review of studies on Biodentine as a vital pulp treatment material and the article is finalized with the summary of some case reports where the material has been used. Özlem Malkondu, Meriç Karapinar Kazandağ, and Ender Kazazoğlu Copyright © 2014 Özlem Malkondu et al. All rights reserved. Nanofibrous Chitosan-Polyethylene Oxide Engineered Scaffolds: A Comparative Study between Simulated Structural Characteristics and Cells Viability Wed, 04 Jun 2014 09:50:01 +0000 3D nanofibrous chitosan-polyethylene oxide (PEO) scaffolds were fabricated by electrospinning at different processing parameters. The structural characteristics, such as pore size, overall porosity, pore interconnectivity, and scaffold percolative efficiency (SPE), were simulated by a robust image analysis. Mouse fibroblast cells (L929) were cultured in RPMI for 2 days in the presence of various samples of nanofibrous chitosan/PEO scaffolds. Cell attachments and corresponding mean viability were enhanced from 50% to 110% compared to that belonging to a control even at packed morphologies of scaffolds constituted from pores with nanoscale diameter. To elucidate the correlation between structural characteristics within the depth of the scaffolds’ profile and cell viability, a comparative analysis was proposed. This analysis revealed that larger fiber diameters and pore sizes can enhance cell viability. On the contrary, increasing the other structural elements such as overall porosity and interconnectivity due to a simultaneous reduction in fiber diameter and pore size through the electrospinning process can reduce the viability of cells. In addition, it was found that manipulation of the processing parameters in electrospinning can compensate for the effects of packed morphologies of nanofibrous scaffolds and can thus potentially improve the infiltration and viability of cells. Mohammad Kazemi Pilehrood, Mandana Dilamian, Mina Mirian, Hojjat Sadeghi-Aliabadi, Laleh Maleknia, Pertti Nousiainen, and Ali Harlin Copyright © 2014 Mohammad Kazemi Pilehrood et al. All rights reserved. Tissue Extracellular Matrix Nanoparticle Presentation in Electrospun Nanofibers Thu, 29 May 2014 09:13:30 +0000 Biomaterials derived from the decellularization of mature tissues retain biological and architectural features that profoundly influence cellular activity. However, the clinical utility of such materials remains limited as the shape and physical properties are difficult to control. In contrast, scaffolds based on synthetic polymers can be engineered to exhibit specific physical properties, yet often suffer from limited biological functionality. This study characterizes composite materials that present decellularized extracellular matrix (DECM) particles in combination with synthetic nanofibers and examines the ability of these materials to influence stem cell differentiation. Mechanical processing of decellularized tissues yielded particles with diameters ranging from 71 to 334 nm. Nanofiber scaffolds containing up to 10% DECM particles (wt/wt) derived from six different tissues were engineered and evaluated to confirm DECM particle incorporation and to measure bioactivity. Scaffolds containing bone, cartilage, and fat promoted osteogenesis at 1 and 3 weeks compared to controls. In contrast, spleen and lung DECM significantly reduced osteogenic outcomes compared to controls. These findings highlight the potential to incorporate appropriate source DECM nanoparticles within nanofiber composites to design a scaffold with bioactivity targeted to specific applications. Matt Gibson, Vince Beachley, Jeannine Coburn, Pierre Alain Bandinelli, Hai-Quan Mao, and Jennifer Elisseeff Copyright © 2014 Matt Gibson et al. All rights reserved. Insights into the Alteration of Osteoblast Mechanical Properties upon Adhesion on Chitosan Thu, 29 May 2014 05:53:15 +0000 Cell adhesion on substrates is accompanied by significant changes in shape and cytoskeleton organization, which affect subsequent cellular and tissue responses, determining the long-term success of an implant. Alterations in osteoblast stiffness upon adhesion on orthopaedic implants with different surface chemical composition and topography are, thus, of central interest in the field of bone implant research. This work aimed to study the mechanical response of osteoblasts upon adhesion on chitosan-coated glass surfaces and to investigate possible correlations with the level of adhesion, spreading, and cytoskeleton reorganization. Using the micropipette aspiration technique, the osteoblast elastic modulus was found higher on chitosan-coated than on uncoated control substrates, and it was found to increase in the course of spreading for both substrates. The cell-surface contact area was measured throughout several time points of adhesion to quantify cell spreading kinetics. Significant differences were found between chitosan and control surfaces regarding the response of cell spreading, while both groups displayed a sigmoidal kinetical behavior with an initially elevated spreading rate which stabilizes in the second hour of attachment. Actin filament structural changes were confirmed after observation with confocal microscope. Biomaterial surface modification can enhance osteoblast mechanical response and induce favorable structural organization for the implant integration. Antonia G. Moutzouri and George M. Athanassiou Copyright © 2014 Antonia G. Moutzouri and George M. Athanassiou. All rights reserved. Effect of Low-Level Laser on Bone Defects Treated with Bovine or Autogenous Bone Grafts: In Vivo Study in Rat Calvaria Wed, 28 May 2014 10:34:15 +0000 Objective. The purpose of this study was to histologically evaluate the effect of low-level laser (LLL) on the healing of critical size defects (CSD) in rat calvaria, filled with autogenous or inorganic bovine bone grafts. Methods. Sixty rats were divided into 6 groups : C (control—filled with blood clot), LLL (low-level laser—GaAlAs, 780 nm, 100 mW, 210 J/cm2, 0.05 cm2; 6 J/point), AB (autogenous bone), ABL (autogenous bone + low-level laser), OB (inorganic bovine bone), and OBL (inorganic bovine bone + LLL). Material and Methods. The animals were killed after 30 days. Histological and histometric analyses were performed by light microscopy. Results. The groups irradiated with laser, LLL (47.67% ± 8.66%), ABL (39.15% ± 16.72%), and OBL (48.57% ± 28.22%), presented greater area of new bone formation than groups C (9.96% ± 4.50%), AB (30.98% ± 16.59%), and OB (11.36% ± 7.89%), which were not irradiated. Moreover, they were significantly better than group C (Kruskal-Wallis test followed by Dunn test, . Conclusion. The laser accelerated the healing of bone defects and the resorption of particles of the graft material. Mércia J. S. Cunha, Luis A. Esper, Michyele C. Sbrana, Paula G. F. P. de Oliveira, Accácio L. do Valle, and Ana Lúcia P. F. de Almeida Copyright © 2014 Mércia J. S. Cunha et al. All rights reserved. Nano-/Microfabrication of Biomaterials Tue, 27 May 2014 09:45:18 +0000 Inn-Kyu Kang, Yoshihiro Ito, and Oh Hyeong Kwon Copyright © 2014 Inn-Kyu Kang et al. All rights reserved. Improvement of the Digestibility of Sulfated Hyaluronans by Bovine Testicular Hyaluronidase: A UV Spectroscopic and Mass Spectrometric Study Tue, 27 May 2014 08:53:28 +0000 Glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are important, natural polysaccharides which occur in biological (connective) tissues and have various biotechnological and medical applications. Additionally, there is increasing evidence that chemically (over)sulfated GAGs possess promising properties and are useful as implant coatings. Unfortunately, a detailed characterization of these GAGs is challenging: although mass spectrometry (MS) is one of the most powerful tools to elucidate the structures of (poly)saccharides, MS is not applicable to high mass polysaccharides, but characteristic oligosaccharides are needed. These oligosaccharides are normally generated by enzymatic digestion. However, chemically modified (particularly sulfated) GAGs are extremely refractive to enzymatic digestion. This study focuses on the investigation of the digestibility of GAGs with different degrees of sulfation by bovine testicular hyaluronidase (BTH). It will be shown by using an adapted spectrophotometric assay that all investigated GAGs can be basically digested if the reaction conditions are carefully adjusted. However, the oligosaccharide yield correlates reciprocally with the number of sulfate residues per polymer repeating unit. Finally, matrix-laser desorption and ionization (MALDI) MS will be used to study the released oligosaccharides and their sulfation patterns. Katharina Lemmnitzer, Jürgen Schiller, Jana Becher, Stephanie Möller, and Matthias Schnabelrauch Copyright © 2014 Katharina Lemmnitzer et al. All rights reserved. Resin Composites Reinforced by Nanoscaled Fibers or Tubes for Dental Regeneration Tue, 27 May 2014 00:00:00 +0000 It has been stated clearly that nanofillers could make an enhancement on the mechanical performances of dental composites. In order to address current shortage of traditional dental composites, fillers in forms of nanofibers or nanotubes are broadly regarded as ideal candidates to greatly increase mechanical performances of dental composites with low content of fillers. In this review, the efforts using nanofibers and nanotubes to reinforce mechanical performances of dental composites, including polymeric nanofibers, metallic nanofibers or nanotubes, and inorganic nanofibers or nanotubes, as well as their researches related, are demonstrated in sequence. The first purpose of current paper was to confirm the enhancement of nanofibers or nanotubes’ reinforcement on the mechanical performances of dental restorative composite. The second purpose was to make a general description about the reinforcement mechanism of nanofibers and nanotubes, especially, the impact of formation of interphase boundary interaction and nanofibers themselves on the advanced mechanical behaviors of the dental composites. By means of the formation of interface interaction and poststretching nanofibers, reinforced effect of dental composites by sorts of nanofibers/nanotubes has been successfully obtained. Xiaoming Li, Wei Liu, Lianwen Sun, Katerina E. Aifantis, Bo Yu, Yubo Fan, Qingling Feng, Fuzhai Cui, and Fumio Watari Copyright © 2014 Xiaoming Li et al. All rights reserved. Reliable Assessment and Quantification of the Fluorescence-Labeled Antisense Oligonucleotides In Vivo Sun, 25 May 2014 10:58:41 +0000 The availability of fluorescent dyes and the advances in the optical systems for in vivo imaging have stimulated an increasing interest in developing new methodologies to study and quantify the biodistribution of labeled agents. However, despite these great achievements, we are facing significant challenges in determining if the observed fluorescence does correspond to the quantity of the dye in the tissues. In fact, although the far-red and near-infrared lights can propagate through several centimetres of tissue, they diffuse within a few millimetres as consequence of the elastic scattering of photons. In addition, when dye-labeled oligonucleotides form stable complex with cationic carriers, a large change in the fluorescence intensity of the dye is observed. Therefore, the measured fluorescence intensity is altered by the tissue heterogeneity and by the fluctuation of dye intensity. Hence, in this study a quantification strategy for fluorescence-labeled oligonucleotides was developed to solve these disadvantageous effects. Our results proved that upon efficient homogenization and dilution with chaotropic agents, such as guanidinium thiocyanate, it is possible to achieve a complete fluorescence intensity recovery. Furthermore, we demonstrated that this method has the advantage of good sensitivity and reproducibility, as well as easy handling of the tissue samples. Maria Chiara Munisso and Tetsuji Yamaoka Copyright © 2014 Maria Chiara Munisso and Tetsuji Yamaoka. All rights reserved. Potency of Fish Collagen as a Scaffold for Regenerative Medicine Sun, 25 May 2014 08:03:51 +0000 Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD) motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine. Shizuka Yamada, Kohei Yamamoto, Takeshi Ikeda, Kajiro Yanagiguchi, and Yoshihiko Hayashi Copyright © 2014 Shizuka Yamada et al. All rights reserved. Histologic Changes of Implanted Gore Bio-A in an Experimental Animal Model Wed, 21 May 2014 06:16:00 +0000 Gore Bio-A has been reported to be an ideal synthetic bioabsorbable scaffold material for hernia repair. The purpose of this study was to determine the effectiveness of Gore Bio-A in soft tissue augmentation. Six New Zealand white rabbits were used in the study. Five subcutaneous pockets were created on the back of the rabbit, and  mm sized square shaped Gore Bio-A sheets, each 1.5 mm, 3 mm, 4.5 mm, 6 mm, and 7.5 mm in thickness, were implanted into each pocket (1 layer to 5 layers). To analyze the morphologic and histologic changes, the implants were harvested 1, 3, and 6 months after implantation. Following the gross analysis, absorption rate was accelerated with increased implant duration and decreased thickness. Histological analysis of the implants demonstrated progressive neovascularization, fibroblast infiltration, and neocollagenation over time. Six months after implantation, Gore Bio-A was almost absorbed and degenerated, not maintaining its volume. Based on this study, Gore Bio-A was revealed as a biocompatible material; however, it is not suitable for soft tissue augmentation because it is absorbed in the process of changing into soft tissue without maintaining its own volume. Therefore, this material is incomplete and needs more study to overcome this limitation. Kwan Koo Yeo, Tae Hwan Park, Jin Hyuk Park, Choong Hyun Chang, June-kyu Kim, and Sang Won Seo Copyright © 2014 Kwan Koo Yeo et al. All rights reserved. Reinforcement of Dental Methacrylate with Glass Fiber after Heated Silane Application Tue, 20 May 2014 00:00:00 +0000 This study evaluated the influence of silane heat treatment and glass fiber fabrication type, industrially treated (I) or pure (P), on flexural and compressive strength of methacrylate resin bars (BISGMA/TEGDMA, 50/50%). Six groups were created: I-sil: I/silanated; P-sil: P-silanated; I-sil/heat: I/silanated heated to 100°; P-sil/heat: P/silanated heated to 100°; (I: I/not silanated; and P: P/not silanated. Specimens were prepared for flexural strength and for compressive strength ) and tested at 0.5 mm/min. Statistical analysis demonstrated the following for flexural strength : I-sil: ; P-sil: ; I-sil/heat: ; P-sil/heat: ; I: . For compressive strength, the following are demonstrated: I-sil: ; P-sil: ; I-sil/heat: ; P-sil/heat: ; and I: . Due to the impossibility of incorporating the stipulated amount of fiber, P group was excluded. Glass fiber treatment with heated silane enhanced flexural and compressive strength of a reinforced dental methacrylate. Rodrigo Borges Fonseca, Marcella Silva de Paula, Isabella Negro Favarão, Amanda Vessoni Barbosa Kasuya, Letícia Nunes de Almeida, Gustavo Adolfo Martins Mendes, and Hugo Lemes Carlo Copyright © 2014 Rodrigo Borges Fonseca et al. All rights reserved. Immunomodulation of Nanoparticles in Nanomedicine Applications Tue, 20 May 2014 00:00:00 +0000 Nanoparticles (NPs) have promising applications in medicine. Immune system is an important protective system to defend organisms from non-self matters. NPs interact with the immune system and modulate its function, leading to immunosuppression or immunostimulation. These modulating effects may bring benefits or danger. Compositions, sizes, and surface chemistry, and so forth, affect these immunomodulations. Here we give an overview of the relationship between the physicochemical properties of NPs, which are candidates to be applied in medicine, and their immunomodulation properties. Qing Jiao, Liwen Li, Qingxin Mu, and Qiu Zhang Copyright © 2014 Qing Jiao et al. All rights reserved. Spider Silk as Guiding Biomaterial for Human Model Neurons Sun, 18 May 2014 06:46:46 +0000 Over the last years, a number of therapeutic strategies have emerged to promote axonal regeneration. An attractive strategy is the implantation of biodegradable and nonimmunogenic artificial scaffolds into injured peripheral nerves. In previous studies, transplantation of decellularized veins filled with spider silk for bridging critical size nerve defects resulted in axonal regeneration and remyelination by invading endogenous Schwann cells. Detailed interaction of elongating neurons and the spider silk as guidance material is unknown. To visualize direct cellular interactions between spider silk and neurons in vitro, we developed an in vitro crossed silk fiber array. Here, we describe in detail for the first time that human (NT2) model neurons attach to silk scaffolds. Extending neurites can bridge gaps between single silk fibers and elongate afterwards on the neighboring fiber. Culturing human neurons on the silk arrays led to an increasing migration and adhesion of neuronal cell bodies to the spider silk fibers. Within three to four weeks, clustered somata and extending neurites formed ganglion-like cell structures. Microscopic imaging of human neurons on the crossed fiber arrays in vitro will allow for a more efficient development of methods to maximize cell adhesion and neurite growth on spider silk prior to transplantation studies. Frank Roloff, Sarah Strauß, Peter M. Vogt, Gerd Bicker, and Christine Radtke Copyright © 2014 Frank Roloff et al. All rights reserved. Enhanced Blood Compatibility of Metallocene Polyethylene Subjected to Hydrochloric Acid Treatment for Cardiovascular Implants Thu, 15 May 2014 00:00:00 +0000 Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly () after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices. Saravana Kumar Jaganathan, Hemanth Mohandas, Gunalan Sivakumar, Palaniappan Kasi, Theertha Sudheer, Sruthi Avineri Veetil, Selvakumar Murugesan, and Eko Supriyanto Copyright © 2014 Saravana Kumar Jaganathan et al. All rights reserved. RhoA Controls Wnt Upregulation on Microstructured Titanium Surfaces Wed, 14 May 2014 00:00:00 +0000 Rough topography enhances the activation of Wnt canonical signaling in vitro, and this mediates its effects on cell differentiation. However, the molecular mechanisms underlying topography-dependent control of Wnt signaling are still poorly understood. As the small GTPase RhoA controls cytoskeletal reorganization and actomyosin-induced tensional forces, we hypothesized that RhoA could affect the activation of Wnt signaling in cells on micropatterned titanium surfaces. G-LISA assay revealed that RhoA activation was higher in C2C12 cells on rough (SLA) surfaces under basal conditions than on smooth (Polished) titanium. Transfection with dominant negative RhoA decreased Wnt activation by normalized TCF-Luc activity on SLA, whilst transfection with constitutively active RhoA increased TCF-Luc activation on Polished titanium. One mM Myosin II inhibitor Blebbistatin increased RhoA activation but decreased Wnt activation on SLA surfaces, indicating that tension-generating structures are required for canonical Wnt modulation on titanium surfaces. Actin inhibitor Cytochalasin markedly enhanced RhoA and TCF-Luc activation on both surfaces and increased the expression of differentiation markers in murine osteoblastic MC3T3 cells. Taken together, these data show that RhoA is upregulated in cells on rough surfaces and it affects the activation of Wnt canonical signaling through Myosin II modulation. Simone Lumetti, Silvia Mazzotta, Sara Ferrillo, Maddalena Piergianni, Marilina Piemontese, Giovanni Passeri, Guido Maria Macaluso, and Carlo Galli Copyright © 2014 Simone Lumetti et al. All rights reserved. Bone Marrow Stem Cells Added to a Hydroxyapatite Scaffold Result in Better Outcomes after Surgical Treatment of Intertrochanteric Hip Fractures Wed, 14 May 2014 00:00:00 +0000 Introduction. Intertrochanteric hip fractures occur in the proximal femur. They are very common in the elderly and are responsible for high rates of morbidity and mortality. The authors hypothesized that adding an autologous bone marrow stem cells concentrate (ABMC) to a hydroxyapatite scaffold and placing it in the fracture site would improve the outcome after surgical fixation of intertrochanteric hip fractures. Material and Methods. 30 patients were randomly selected and divided into 2 groups of 15 patients, to receive either the scaffold enriched with the ABMC (Group A) during the surgical procedure, or fracture fixation alone (Group B). Results. There was a statistically significant difference in favor of group A at days 30, 60, and 90 for Harris Hip Scores (HHS), at days 30 and 60 for VAS pain scales, for bedridden period and time taken to start partial and total weight bearing (). Discussion. These results show a significant benefit of adding a bone marrow enriched scaffold to surgical fixation in intertrochanteric hip fractures, which can significantly reduce the associated morbidity and mortality rates. Conclusion. Bone marrow stem cells added to a hydroxyapatite scaffold result in better outcomes after surgical treatment of intertrochanteric hip fractures. Joao Torres, Manuel Gutierres, M. Ascenção Lopes, J. Domingos Santos, A. T. Cabral, R. Pinto, and Carola van Eck Copyright © 2014 Joao Torres et al. All rights reserved. Biodegradable and Elastomeric Poly(glycerol sebacate) as a Coating Material for Nitinol Bare Stent Tue, 13 May 2014 12:08:20 +0000 We synthesized and evaluated biodegradable and elastomeric polyesters (poly(glycerol sebacate) (PGS)) using polycondensation between glycerol and sebacic acid to form a cross-linked network structure without using exogenous catalysts. Synthesized materials possess good mechanical properties, elasticity, and surface erosion biodegradation behavior. The tensile strength of the PGS was as high as 0.28 ± 0.004 MPa, and Young's modulus was 0.122 ± 0.0003 MPa. Elongation was as high as 237.8 ± 0.64%, and repeated elongation behavior was also observed to at least three times the original length without rupture. The water-in-air contact angles of the PGS surfaces were about 60°. We also analyzed the properties of an electrospray coating of biodegradable PGS on a nitinol stent for the purpose of enhancing long-term patency for the therapeutic treatment of varicose veins disease. The surface morphology and thickness of coating layer could be controlled by adjusting the electrospraying conditions and solution parameters. Min Ji Kim, Moon Young Hwang, JiHeung Kim, and Dong June Chung Copyright © 2014 Min Ji Kim et al. All rights reserved. Antimicrobial and Controlled Release Studies of a Novel Nystatin Conjugated Iron Oxide Nanocomposite Mon, 12 May 2014 08:12:41 +0000 Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications. Samer Hasan Hussein-Al-Ali, Mohamed E. El Zowalaty, Aminu Umar Kura, Benjamin Geilich, Sharida Fakurazi, Thomas J. Webster, and Mohd Zobir Hussein Copyright © 2014 Samer Hasan Hussein-Al-Ali et al. All rights reserved. Substituted Hydroxyapatites with Antibacterial Properties Sun, 11 May 2014 08:55:05 +0000 Reconstructive surgery is presently struggling with the problem of infections located within implantation biomaterials. Of course, the best antibacterial protection is antibiotic therapy. However, oral antibiotic therapy is sometimes ineffective, while administering an antibiotic at the location of infection is often associated with an unfavourable ratio of dosage efficiency and toxic effect. Thus, the present study aims to find a new factor which may improve antibacterial activity while also presenting low toxicity to the human cells. Such factors are usually implemented along with the implant itself and may be an integral part of it. Many recent studies have focused on inorganic factors, such as metal nanoparticles, salts, and metal oxides. The advantages of inorganic factors include the ease with which they can be combined with ceramic and polymeric biomaterials. The following review focuses on hydroxyapatites substituted with ions with antibacterial properties. It considers materials that have already been applied in regenerative medicine (e.g., hydroxyapatites with silver ions) and those that are only at the preliminary stage of research and which could potentially be used in implantology or dentistry. We present methods for the synthesis of modified apatites and the antibacterial mechanisms of various ions as well as their antibacterial efficiency. Joanna Kolmas, Ewa Groszyk, and Dagmara Kwiatkowska-Różycka Copyright © 2014 Joanna Kolmas et al. All rights reserved. Electrospun Polyhydroxybutyrate and Poly(L-lactide-co-ε-caprolactone) Composites as Nanofibrous Scaffolds Thu, 08 May 2014 07:38:21 +0000 Electrospinning can produce nanofibrous scaffolds that mimic the architecture of the extracellular matrix and support cell attachment for tissue engineering applications. In this study, fibrous membranes of polyhydroxybutyrate (PHB) with various loadings of poly(L-lactide-co--caprolactone) (PLCL) were successfully prepared by electrospinning. In comparison to PLCL scaffolds, PLCL blends with PHB exhibited more irregular fibre diameter distributions and higher average fibre diameters but there were no significant differences in pore size. PLCL/PHB scaffolds were more hydrophilic (<120°) with significantly reduced tensile strength (ca. 1 MPa) compared to PLCL scaffolds ( and  MPa). Increasing PLCL loading in PHB/PLCL scaffolds significantly increased the extension at break, (4–6-fold). PLCL/PHB scaffolds supported greater adhesion and proliferation of olfactory ensheathing cells (OECs) than those exhibiting asynchronous growth on culture plates. Mitochondrial activity of cells cultivated on the electrospun blended membranes was enhanced compared to those grown on PLCL and PHB scaffolds (212, 179, and 153%, resp.). Analysis showed that PLCL/PHB nanofibrous membranes promoted cell cycle progression and reduced the onset of necrosis. Thus, electrospun PLCL/PHB composites promoted adhesion and proliferation of OECs when compared to their individual PLCL and PHB components suggesting potential in the repair and engineering of nerve tissue. Donraporn Daranarong, Rodman T. H. Chan, Nico S. Wanandy, Robert Molloy, Winita Punyodom, and L. John R. Foster Copyright © 2014 Donraporn Daranarong et al. All rights reserved. Biomaterials in Cardiovascular Research: Applications and Clinical Implications Thu, 08 May 2014 00:00:00 +0000 Cardiovascular biomaterials (CB) dominate the category of biomaterials based on the demand and investments in this field. This review article classifies the CB into three major classes, namely, metals, polymers, and biological materials and collates the information about the CB. Blood compatibility is one of the major criteria which limit the use of biomaterials for cardiovascular application. Several key players are associated with blood compatibility and they are discussed in this paper. To enhance the compatibility of the CB, several surface modification strategies were in use currently. Some recent applications of surface modification technology on the materials for cardiovascular devices were also discussed for better understanding. Finally, the current trend of the CB, endothelization of the cardiac implants and utilization of induced human pluripotent stem cells (ihPSCs), is also presented in this review. The field of CB is growing constantly and many new investigators and researchers are developing interest in this domain. This review will serve as a one stop arrangement to quickly grasp the basic research in the field of CB. Saravana Kumar Jaganathan, Eko Supriyanto, Selvakumar Murugesan, Arunpandian Balaji, and Manjeesh Kumar Asokan Copyright © 2014 Saravana Kumar Jaganathan et al. All rights reserved. Bond Strengths of Silorane- and Methacrylate-Based Composites to Various Underlying Materials Wed, 07 May 2014 06:50:36 +0000 Objective. To evaluate shear bond strength (SBS) values of a methacrylate (FZ 250) and a silorane-based (FS) resin composite to various underlying materials. Materials and Methods. A total of 80 samples were prepared with four different underlying materials; a flowable (FLC) and a bulk-fill flowable composite (BFC), and a conventional (CGIC) and resin modified glass-ionomer cement (RMGIC). These underlying materials were laminated plus to methacrylate or silorane-based resin composites . To evaluate the specimens SBS values were evaluated with a universal testing machine (cross-head speed; 1.0 mm/min). Statistical comparisons were carried out using two-way ANOVA and Tukey’s post hoc test with a significance level of . Results. SBS values for FZ250 were significantly higher than for FS for all of the underlying materials tested . SBS values of FZ250 to BFC were significantly higher than to all other materials , whereas SBS values of FS did not vary significantly according to underlying material . Conclusion. The use of FS in conjunction with any of the tested materials showed lower SBS than the FZ 250. Also, new low elastic modulus liner BFC presented slightly good interfacial adhesion so, the usage of BFC as an underlying material may be preferable for FZ 250. Sezin Ozer, Emine Sen Tunc, and Nihan Gonulol Copyright © 2014 Sezin Ozer et al. All rights reserved. Osteoconductive Potential of Barrier NanoSiO2 PLGA Membranes Functionalized by Plasma Enhanced Chemical Vapour Deposition Sun, 04 May 2014 13:41:41 +0000 The possibility of tailoring membrane surfaces with osteoconductive potential, in particular in biodegradable devices, to create modified biomaterials that stimulate osteoblast response should make them more suitable for clinical use, hopefully enhancing bone regeneration. Bioactive inorganic materials, such as silica, have been suggested to improve the bioactivity of synthetic biopolymers. An in vitro study on HOB human osteoblasts was performed to assess biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co-glycolide) (PLGA) membranes, prior to clinical use. A 15 nm SiO2 layer was deposited by plasma enhanced chemical vapour deposition (PECVD), onto a resorbable PLGA membrane. Samples were characterized by X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared spectroscopy (FT-IR). HOB cells were seeded on sterilized test surfaces where cell morphology, spreading, actin cytoskeletal organization, and focal adhesion expression were assessed. As proved by the FT-IR analysis of samples, the deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the composition and other characteristics of the organic membrane. A temporal and spatial reorganization of cytoskeleton and focal adhesions and morphological changes in response to SiO2 nanolayer were identified in our model. The novedous SiO2 deposition method is compatible with the standard sterilization protocols and reveals as a valuable tool to increase bioactivity of resorbable PLGA membranes. Antonia Terriza, Jose I. Vilches-Pérez, Emilio de la Orden, Francisco Yubero, Juan L. Gonzalez-Caballero, Agustin R. González-Elipe, José Vilches, and Mercedes Salido Copyright © 2014 Antonia Terriza et al. All rights reserved. Complete Cell Killing by Applying High Hydrostatic Pressure for Acellular Vascular Graft Preparation Wed, 30 Apr 2014 07:32:07 +0000 Pressure treatment has been developed in tissue engineering application. Although the tissue scaffold prepared by a ultrahydrostatic pressure treatment has been reported, an excessive pressure has a potential to disrupt a structure of extracellular matrix through protein denaturation. It is important to understand the suitable low-pressure condition and mechanisms for cell killing. In this study, cellular morphology, mitochondria activity, and membrane permeability of mammalian cells with various pressure treatments were investigated with in vitro models. When the cells were treated with a pressure of 100 MPa for 10 min, cell morphology and adherence were the same as an untreated cells. Dehydrogenase activity in mitochondria was almost the same as untreated cells. On the other hand, when the cells were treated with the pressure of more than 200 MPa, the cells did not adhere, and the dehydrogenase activity was completely suppressed. However, green fluorescence was observed in the live/dead staining images, and the cells were completely stained as red after above 500 MPa. That is, membrane permeability was disturbed with the pressure treatment of above 500 MPa. These results indicated that the pressure of 200 MPa for 10 min was enough to induce cell killing through inactivation of mitochondria activity. Atsushi Mahara, Naoki Morimoto, Takahiro Sakuma, Toshiya Fujisato, and Tetsuji Yamaoka Copyright © 2014 Atsushi Mahara et al. All rights reserved. Vertical Ridge Augmentation of the Atrophic Posterior Mandible with Sandwich Technique: Bone Block from the Chin Area versus Corticocancellous Bone Block Allograft—Clinical and Histological Prospective Randomized Controlled Study Tue, 29 Apr 2014 09:15:49 +0000 The aim of the present study is to compare the histological aspects of bone formation in atrophic posterior mandibles augmented by autologous bone block from chin area with corticocancellous bone block allograft used as inlays with the sandwich technique. Materials and Methods. Sixteen patients with bilateral partial edentulism in the posterior mandible were selected. The residual bone height, preliminarily measured by computed tomography scans, ranged between 5 and 7 mm from the inferior alveolar nerve. All patients required regeneration procedure with autologous bone block from chin area (control group) versus bone block allograft Puros (Zimmer Dental, 1900 Aston Avenue, Carlsbad, CA, USA) (test group). Histological and histomorphometric samples were collected at the time of implant positioning in order to analyze the percentage of newly formed bone, the residual graft material, and marrow spaces/soft tissue. Results. No statistically significant differences between the two groups were found regarding the percentage of newly formed bone. The percentage of residual grafted material was significantly higher in the test group, whilst the percentage of marrow spaces was higher in control group. Conclusions. In conclusion, both procedures supported good results, although the use of bone blocks allograft was less invasive and preferable than harvesting bone from the mental symphysis. Luigi Laino, Giovanna Iezzi, Adriano Piattelli, Lorenzo Lo Muzio, and Marco Cicciù Copyright © 2014 Luigi Laino et al. All rights reserved. Artificial Extracellular Matrices with Oversulfated Glycosaminoglycan Derivatives Promote the Differentiation of Osteoblast-Precursor Cells and Premature Osteoblasts Mon, 28 Apr 2014 06:21:12 +0000 Sulfated glycosaminoglycans (GAG) are components of the bone marrow stem cell niche and to a minor extent of mature bone tissue with important functions in regulating stem cell lineage commitment and differentiation. We anticipated that artificial extracellular matrices (aECM) composed of collagen I and synthetically oversulfated GAG derivatives affect preferentially the differentiation of osteoblast-precursor cells and early osteoblasts. A set of gradually sulfated chondroitin sulfate and hyaluronan derivatives was used for the preparation of aECM. All these matrices were analysed with human bone marrow stromal cells to identify the most potent aECM and to determine the influence of the degree and position of sulfate groups and the kind of disaccharide units on the osteogenic differentiation. Oversulfated GAG derivatives with a sulfate group at the C-6 position of the N-acetylglycosamine revealed the most pronounced proosteogenic effect as determined by tissue nonspecific alkaline phosphatase activity and calcium deposition. A subset of the aECM was further analysed with different primary osteoblasts and cell lines reflecting different maturation stages to test whether the effect of sulfated GAG derivatives depends on the maturation status of the cells. It was shown that the proosteogenic effect of aECM was most prominent in early osteoblasts. Ute Hempel, Carolin Preissler, Sarah Vogel, Stephanie Möller, Vera Hintze, Jana Becher, Matthias Schnabelrauch, Martina Rauner, Lorenz C. Hofbauer, and Peter Dieter Copyright © 2014 Ute Hempel et al. All rights reserved. Synthesis and Evaluation of Tetramethylguanidinium-Polyethylenimine Polymers as Efficient Gene Delivery Vectors Thu, 24 Apr 2014 12:23:40 +0000 Previously, we demonstrated that 6-(N,N,N′,N′-tetramethylguanidinium chloride)-hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced transfection efficiency and cell viability. Here, in the present study, we have synthesized a series of N,N,N′,N′-tetramethylguanidinium-polyethylenimine (TP1-TP5) polymers via a single-step reaction involving peripheral primary amines of bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These polymers were found to interact efficiently with negatively charged pDNA and formed stable complexes in the size range of ~240–450 nm. Acid-base titration profiles revealed improved buffering capacity of TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher transfection efficiency and cell viability with one of the complexes, TP2/pDNA complex, exhibited the highest transfection efficiency (~1.4–2.3-fold) outcompeting native bPEI and the commercially available transfection reagent, Lipofectamine 2000. Compared to previously reported THP polymers, the transfection efficiency of TP/pDNA complexes was found to be lower, as examined by flow cytometry. These results highlight the importance of the hydrophobic C-6 linker in THP polymers in forming compact nanostructures with pDNA, which might lead to efficient uptake and internalization of the complexes; however, the projected TP polymers offer an advantage of their rapid and economical one-step synthesis. Manohar Mahato, Santosh Yadav, Pradeep Kumar, and Ashwani Kumar Sharma Copyright © 2014 Manohar Mahato et al. All rights reserved. Surface Characteristics and Bioactivity of a Novel Natural HA/Zircon Nanocomposite Coated on Dental Implants Wed, 16 Apr 2014 16:45:25 +0000 The surface characteristics of implant which influence the speed and strength of osseointegration include surface chemistry, crystal structure and crystallinity, roughness, strain hardening, and presence of impurities. The aim of this study was to evaluate the bioactivity and roughness of a novel natural hydroxyapatite/zircon (NHA/zircon) nanobiocomposite, coated on 316L stainless steel (SS) soaked in simulated body fluid (SBF). NHA/zircon nanobiocomposite was fabricated with 0 wt.%, 5 wt.%, 10 wt.%, and 15 wt.% of zircon in NHA using ball mill for 20 minutes. The composite mixture was coated on 316L SS using plasma spray method. The results are estimated using the scanning electron microscopy (SEM) observation to evaluate surface morphology, X-ray diffraction (XRD) to analyze phase composition, and transmission electron microscopy (TEM) technique to evaluate the shape and size of prepared NHA. Surfaces roughness tester was performed to characterize the coated nanocomposite samples. The maximum average (14.54 μm) was found in the NHA 10 wt.% of zircon coating. In addition, crystallinity () was measured by XRD data, which indicated the minimum value ( = 41.1%) for the sample containing 10 wt.% of zircon. Maximum bioactivity occurred in the sample containing 10 wt.% of zircon, which was due to two reasons: first, the maximum roughness and, second, the minimum crystallinity of nanobiocomposite coating. Ebrahim Karamian, Amirsalar Khandan, Mahmood Reza Kalantar Motamedi, and Hesam Mirmohammadi Copyright © 2014 Ebrahim Karamian et al. All rights reserved. Mechanical Stress Stimulates the Osteo/Odontoblastic Differentiation of Human Stem Cells from Apical Papilla via ERK 1/2 and JNK MAPK Pathways Tue, 15 Apr 2014 00:00:00 +0000 Background Information. Stem cells from apical papilla (SCAPs) are a potent candidate for the apexogenesis/apexification due to their multiple differentiation capacity. During the orthodontic treatment of developing teeth, SCAPs in vivo are usually subjected to the cyclic stress induced by compression forces. However, it remains unclear whether mechanical stress can affect the proliferation and differentiation of human SCAPs. Results. Human SCAPs were isolated and stimulated by 200 g mechanical stimuli for 30 min and their proliferation and differentiation capacity were evaluated in vitro at different time points. MTT and FCM results demonstrated that cell proliferation was enhanced, while TEM findings showed the morphological and ultrastructural changes in stress-treated SCAPs. ALP activity and mineralization capacity of stress-treated SCAPs were upregulated . In the meantime, higher odontogenic and osteogenic differentiation were found in stress-treated SCAPs by real-time RT-PCR and Western blot, as indicated by the expression of related markers at both mRNA and protein levels. Moreover, the protein expressions of pJNK and pERK MAPK pathways were upregulated. Conclusion. Together, these findings suggest that mechanical stress is an important factor affecting the proliferation and differentiation of SCAPs via the activation of ERK and JNK signaling pathway. Chao Mu, Taohong Lv, Zilu Wang, Shu Ma, Jie Ma, Jin Liu, Jinhua Yu, and Jinquan Mu Copyright © 2014 Chao Mu et al. All rights reserved. Methoxy-Poly(ethylene glycol) Modified Poly(L-lactide) Enhanced Cell Affinity of Human Bone Marrow Stromal Cells by the Upregulation of 1-Cadherin and Delta-2-catenin Mon, 14 Apr 2014 13:57:08 +0000 Poly(l-lactide) (PLLA), a versatile biodegradable polymer, is one of the most commonly-used materials for tissue engineering applications. To improve cell affinity for PLLA, poly(ethylene glycol) (PEG) was used to develop diblock copolymers. Human bone marrow stromal cells (hBMSCs) were cultured on MPEG-b-PLLA copolymer films to determine the effects of modification on the attachment and proliferation of hBMSC. The mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analyzed using RT-qPCR to understand the underlying mechanisms. It was found that MPEG-b-PLLA copolymer films significantly improved cell adhesion, extension, and proliferation. This was found to be related to the significant upregulation of two adhesion genes, CDH1 and CTNND2, which encode 1-cadherin and delta-2-catenin, respectively, two key components for the cadherin-catenin complex. In summary, MPEG-b-PLLA copolymer surfaces improved initial cell adhesion by stimulation of adhesion molecule gene expression. Xueli Mao, Zetao Chen, Junqi Ling, Jingjing Quan, Hui Peng, and Yin Xiao Copyright © 2014 Xueli Mao et al. All rights reserved. Application of Ultrasound on Monitoring the Evolution of the Collagen Fiber Reinforced nHAC/CS Composites In Vivo Mon, 14 Apr 2014 09:03:00 +0000 To date, fiber reinforce scaffolds have been largely applied to repair hard and soft tissues. Meanwhile, monitoring the scaffolds for long periods in vivo is recognized as a crucial issue before its wide use. As a consequence, there is a growing need for noninvasive and convenient methods to analyze the implantation remolding process in situ and in real time. In this paper, diagnostic medical ultrasound was used to monitor the in vivo bone formation and degradation process of the novel mineralized collagen fiber reinforced composite which is synthesized by chitosan (CS), nanohydroxyapatite (nHA), and collagen fiber (Col). To observe the impact of cells on bone remodeling process, the scaffolds were planted into the back of the SD rats with and without rat bone mesenchymal stem cells (rBMSCs). Systematic data of scaffolds in vivo was extracted from ultrasound images. Significant consistency between the data from the ultrasound and DXA could be observed . This indicated that ultrasound may serve as a feasible alternative for noninvasive monitoring the evolution of scaffolds in situ during cell growth. Yan Chen, Yuting Yan, Xiaoming Li, He Li, Huiting Tan, Huajun Li, Yanwen Zhu, Philipp Niemeyer, Matin Yaega, and Bo Yu Copyright © 2014 Yan Chen et al. All rights reserved. Reduction-Triggered Breakable Micelles of Amphiphilic Polyamide Amine-g-Polyethylene Glycol for Methotrexate Delivery Sun, 13 Apr 2014 16:13:19 +0000 Reduction-triggered breakable polymeric micelles incorporated with MTX were prepared using amphiphilic PAA-g-PEG copolymers having S–S bonds in the backbone. The micelles were spherical with diameters less than 70 nm. The micelles could encapsulate the hydrophobic MTX in the hydrophobic core. The drug loading content and drug loading efficiency of the micelles were highly dependent on the copolymer chemical structure, ranging from 2.9 to 7.5% and 31.9 to 82.5%, respectively. Both the drug loading content and drug loading efficiency increased along with more hydrophobic segments in the copolymers. In normal circumstance, these micelles were capable of keeping stable and hold most of the MTX in the core, stabilizing the incorporated MTX through the stacking with the phenyl groups in the backbone of the copolymers. In reductive environments that mimicked the intracellular compartments, the entire MTX payload could be quickly released due to the reduction-triggered breakage of the micelles. These micelles showed good antiproliferative activity against several cancer cell lines, including KB, 4T-1 and HepG2, especially within the low drug concentration scope. Yihang Huang, Jun Liu, Yani Cui, Huanan Li, Yong Sun, Yujiang Fan, and Xingdong Zhang Copyright © 2014 Yihang Huang et al. All rights reserved. Suppressive Effects of D-Glucosamine on the 5-HT Sensitive Nociceptive Units in the Rat Tooth Pulpal Nerve Sun, 13 Apr 2014 00:00:00 +0000 It is well known that D-glucosamine hydrochloride (DGL) has a variety of biological activities and is regarded as a nutritional supplement effective in improving various disorders, including osteoarthritis and atherosclerosis. Although it has been reported that DGL has a significant pain relief effect in treating osteoarthritis, little is known about the characteristics of the effects of this compound on dental pain. The present study was undertaken to evaluate the applicability of DGL as a medicament to control pulpalgia. Using an in vitro rat mandible-inferior alveolar nerve preparation (jaw-nerve preparation), we evaluated the effects of DGL on 5-hydroxytryptamine (5-HT) sensitive nociceptive responses in the tooth pulpal nerve. 5-HT-induced nociceptive responses were fairly suppressed by direct application of DGL, suggesting that DGL have a pain relief effect on patients with dental pain. Kei Kaida, Hiromi Yamashita, Kazuo Toda, and Yoshihiko Hayashi Copyright © 2014 Kei Kaida et al. All rights reserved. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry Thu, 10 Apr 2014 09:31:29 +0000 Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw. Takashi Matsuura, Kentaro Tokutomi, Michiko Sasaki, Michitsuna Katafuchi, Emiri Mizumachi, and Hironobu Sato Copyright © 2014 Takashi Matsuura et al. All rights reserved. Outer Electrospun Polycaprolactone Shell Induces Massive Foreign Body Reaction and Impairs Axonal Regeneration through 3D Multichannel Chitosan Nerve Guides Wed, 09 Apr 2014 14:10:24 +0000 We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts. Sven Duda, Lutz Dreyer, Peter Behrens, Soenke Wienecke, Tanmay Chakradeo, Birgit Glasmacher, and Kirsten Haastert-Talini Copyright © 2014 Sven Duda et al. All rights reserved. Dried Fruit of the Luffa Sponge as a Source of Chitin for Applications as Skin Substitutes Wed, 09 Apr 2014 09:00:03 +0000 LUFFACHITIN obtained from the residue of the sponge-like dried fruit of Luffa aegyptiaca was developed as a weavable skin substitute in this study. A chemical analysis revealed that LUFFACHITIN was composed of a copolymer containing N-acetyl-glucosamine (~40%) as a major monomer with a filamentary structure as demonstrated by both optical and scanning electron microscopy. The pulp-like white residue of the sponge-like dried fruit of Luffa aegyptiaca after treatment was then woven into a thin, porous membrane by filtration and lyophilization as a skin substitute for conducting wound-healing study on rats. The results indicated that the LUFFACHITIN membrane showed significant wound-healing enhancement (25 days to complete healing) compared to cotton gauze (>30 days), but not inferior to that of SACCHACHITIN. Furthermore, the LUFFACHITIN membrane had advantages of having a high yield, better physical properties for fabrication, and a more attractive appearance. Ping-Lun Jiang, Mei-Yin Chien, Ming-Thau Sheu, Yi-You Huang, Meng-Hsun Chen, Ching-Hua Su, and Der-Zen Liu Copyright © 2014 Ping-Lun Jiang et al. All rights reserved. Solubility of Two Resin Composites in Different Mouthrinses Mon, 07 Apr 2014 16:29:59 +0000 Aim. This study aimed to compare the solubility of a universal restorative resin composite (Filtek Z250; FZ250) and a silorane-based resin composite (Filtek Silorane; FS) after immersion in alcohol-containing mouthrinse, alcohol-free mouthrinse, and artificial saliva. Methods. 30 discs (10 mm × 1 mm) were prepared from each material and desiccated until a constant mass was obtained. Specimens were immersed in the test solutions for two days and desiccated again. Solubility was calculated based on the change in weight of each specimen before and after immersion. Data was analyzed using two-way ANOVA and Tukey’s Post Hoc test . Results. Solubility values for both resin composites were the highest in the alcohol-containing mouthrinse. FZ250 showed greater solubility than FS; the difference was only significant in artificial saliva. Conclusion. Both resin-composite materials tested exhibited some degree of solubility in each of the test solutions. The use of an alcohol-free mouthrinse may be preferable for patients with extensive composite restorations. Sezin Ozer, Emine Sen Tunc, Nuray Tuloglu, and Sule Bayrak Copyright © 2014 Sezin Ozer et al. All rights reserved. Biological Safety of Fish (Tilapia) Collagen Mon, 07 Apr 2014 06:53:08 +0000 Marine collagen derived from fish scales, skin, and bone has been widely investigated for application as a scaffold and carrier due to its bioactive properties, including excellent biocompatibility, low antigenicity, and high biodegradability and cell growth potential. Fish type I collagen is an effective material as a biodegradable scaffold or spacer replicating the natural extracellular matrix, which serves to spatially organize cells, providing them with environmental signals and directing site-specific cellular regulation. This study was conducted to confirm the safety of fish (tilapia) atelocollagen for use in clinical application. We performed in vitro and in vivo biological studies of medical materials to investigate the safety of fish collagen. The extract of fish collagen gel was examined to clarify its sterility. All present sterility tests concerning bacteria and viruses (including endotoxin) yielded negative results, and all evaluations of cell toxicity, sensitization, chromosomal aberrations, intracutaneous reactions, acute systemic toxicity, pyrogenic reactions, and hemolysis were negative according to the criteria of the ISO and the Ministry of Health, Labour and Welfare. The present study demonstrated that atelocollagen prepared from tilapia is a promising biomaterial for use as a scaffold in regenerative medicine. Kohei Yamamoto, Kazunari Igawa, Kouji Sugimoto, Yuu Yoshizawa, Kajiro Yanagiguchi, Takeshi Ikeda, Shizuka Yamada, and Yoshihiko Hayashi Copyright © 2014 Kohei Yamamoto et al. All rights reserved. Glycosaminoglycan Monosaccharide Blocks Analysis by Quantum Mechanics, Molecular Dynamics, and Nuclear Magnetic Resonance Mon, 07 Apr 2014 06:49:57 +0000 Glycosaminoglycans (GAGs) play an important role in many biological processes in the extracellular matrix. In a theoretical approach, structures of monosaccharide building blocks of natural GAGs and their sulfated derivatives were optimized by a B3LYP6311ppdd//B3LYP/6-31+G(d) method. The dependence of the observed conformational properties on the applied methodology is described. NMR chemical shifts and proton-proton spin-spin coupling constants were calculated using the GIAO approach and analyzed in terms of the method's accuracy and sensitivity towards the influence of sulfation, O1-methylation, conformations of sugar ring, and ω dihedral angle. The net sulfation of the monosaccharides was found to be correlated with the 1H chemical shifts in the methyl group of the N-acetylated saccharides both theoretically and experimentally. The ω dihedral angle conformation populations of free monosaccharides and monosaccharide blocks within polymeric GAG molecules were calculated by a molecular dynamics approach using the GLYCAM06 force field and compared with the available NMR and quantum mechanical data. Qualitative trends for the impact of sulfation and ring conformation on the chemical shifts and proton-proton spin-spin coupling constants were obtained and discussed in terms of the potential and limitations of the computational methodology used to be complementary to NMR experiments and to assist in experimental data assignment. Sergey A. Samsonov, Stephan Theisgen, Thomas Riemer, Daniel Huster, and M. Teresa Pisabarro Copyright © 2014 Sergey A. Samsonov et al. All rights reserved. The Morphology and Functions of Articular Chondrocytes on a Honeycomb-Patterned Surface Sun, 06 Apr 2014 12:20:46 +0000 The present study investigated the potential of a novel micropatterned substrate for neocartilage formation. Articular chondrocytes were cultured on poly(ɛ-caprolactone) materials whose surfaces were either flat or honeycomb-patterned. The latter was prepared using a novel self-organization technique, while the former, was prepared by spin-coating. The chondrocytes attached and proliferated on both surfaces. On the honeycomb films, chondrocytes were found at the top surface and encased within the 10 μm pores. Meanwhile, chondrocytes on the spin-coated surface flattened out. Accumulation of DNA and keratin sulphate was comparatively higher on the honeycomb films within the first 7 days. At their respective peaks, DNA concentration increased on the honeycomb and flat surfaces by approximately 210% and 400% of their day 1 values, respectively. However, cultures on the flat surface took longer to peak. Extracellular Matrix (ECM) concentrations peaked at 900% and 320% increases for the honeycomb and flat cultures. Type II collagen was upregulated on the honeycomb and flat surfaces by as much as 28% and 25% of their day 1 values, while aggrecan was downregulated with time, by 3.4% and 7.4%. These initial results demonstrate the potential usefulness of honeycomb-based scaffolds during early cultures neocartilage and soft tissue engineering. Joshua O. Eniwumide, Masaru Tanaka, Nobuhiro Nagai, Yuka Morita, Joost de Bruijn, Sadaaki Yamamoto, Shin Onodera, Eiji Kondo, Kazunori Yasuda, and Masatsugu Shimomura Copyright © 2014 Joshua O. Eniwumide et al. All rights reserved. Fabrication and Characteristics of Chitosan Sponge as a Tissue Engineering Scaffold Sun, 06 Apr 2014 11:42:29 +0000 Cells, growth factors, and scaffolds are the three main factors required to create a tissue-engineered construct. After the appearance of bovine spongiform encephalopathy (BSE), considerable attention has therefore been focused on nonbovine materials. In this study, we examined the properties of a chitosan porous scaffold. A porous chitosan sponge was prepared by the controlled freezing and lyophilization of different concentrations of chitosan solutions. The materials were examined by scanning electron microscopy, and the porosity, tensile strength, and basic fibroblast growth factor (bFGF) release profiles from chitosan sponge were examined in vitro. The morphology of the chitosan scaffolds presented a typical microporous structure, with the pore size ranging from 50 to 200 μm. The porosity of chitosan scaffolds with different concentrations was approximately 75–85%. A decreasing tendency for porosity was observed as the concentration of the chitosan increased. The relationship between the tensile properties and chitosan concentration indicated that the ultimate tensile strength for the sponge increased with a higher concentration. The in vitro bFGF release study showed that the higher the concentration of chitosan solution became, the longer the releasing time of the bFGF from the chitosan sponge was. Takeshi Ikeda, Kahori Ikeda, Kouhei Yamamoto, Hidetaka Ishizaki, Yuu Yoshizawa, Kajiro Yanagiguchi, Shizuka Yamada, and Yoshihiko Hayashi Copyright © 2014 Takeshi Ikeda et al. All rights reserved. Induction of Reparative Dentin Formation on Exposed Dental Pulp by Dentin Phosphophoryn/Collagen Composite Sun, 06 Apr 2014 09:28:04 +0000 The ultimate goal of vital pulp therapy is to regenerate rapidly dentin possessing an excellent quality using a biocompatible, bioactive agent. Dentin phosphophoryn (DPP), the most abundant noncollagenous polyanionic protein in dentin, cross-linked to atelocollagen fibrils was applied to direct pulp capping in rats. After 1, 2, and 3 weeks, the teeth applied were examined on the induction of reparative dentin formation and the response of pulp tissue, compared to calcium hydroxide-based agent conventionally used. The reparative dentin formation induced by DPP/collagen composite was more rapid than by calcium hydroxide. In the morphometrical analysis, the formation rate of reparative dentin by DPP/collagen composite was approximately the same as that by calcium hydroxide at 3 weeks. Nevertheless, the compactness of reparative dentin formed by DPP/collagen composite was much superior to what resulted from calcium hydroxide. Also, DPP/collagen composite showed high covering ability of exposed pulp. Moreover, DPP/collagen composite led only to slight pulp inflammation at the beginning whereas calcium hydroxide formed necrotic layer adjacent to the material and induced severe inflammation in pulp tissue at 1 week. The present study demonstrates a potential for DPP/collagen composite as a rapid biocompatible inducer for the formation of reparative dentin of excellent quality in rats. Toshiyuki Koike, Mohammad Ali Akbor Polan, Masanobu Izumikawa, and Takashi Saito Copyright © 2014 Toshiyuki Koike et al. All rights reserved. Effect of Ultrasonication on Physical Properties of Mineral Trioxide Aggregate Tue, 01 Apr 2014 16:09:32 +0000 Aim. To evaluate the effect on physical properties of Mineral Trioxide Aggregate (MTA) of using direct hand compaction during placement and when using hand compaction with indirect ultrasonic activation with different application times. Methods. One hundred acrylic canals were obturated in 3 increments with MTA in sample sizes of 10. One group was obturated by hand with an endodontic plugger and the remainder obturated with indirect ultrasonic application, with times ranging from 2 seconds to 18 seconds per increment. Microhardness values, dye penetration depths, and radiographs of the samples were evaluated. Results. As ultrasonic application time per increment increased, microhardness values fell significantly while dye penetration values increased . Microhardness of MTA ultrasonicated for 2 seconds was significantly higher than hand compaction . Most radiographic voids were visible in the hand-compacted group , which also had higher dye penetration depths than the 2-second ultrasonicated samples. Ultrasonication of MTA for 10–18 seconds resulted in significantly more voids than 2–8 seconds of ultrasonication . Conclusion. The use of ultrasonics with MTA improved the compaction and flow of MTA, but excessive ultrasonication adversely affected MTA properties. A time of 2 seconds of ultrasonication per increment presented the best compromise between microhardness values, dye penetration depths, and lack of radiographic voids. Peter Parashos, Amanda Phoon, and Chankhrit Sathorn Copyright © 2014 Peter Parashos et al. All rights reserved. Characterization of Genipin-Modified Dentin Collagen Tue, 25 Mar 2014 11:23:04 +0000 Application of biomodification techniques to dentin can improve its biochemical and biomechanical properties. Several collagen cross-linking agents have been reported to strengthen the mechanical properties of dentin. However, the characteristics of collagen that has undergone agent-induced biomodification are not well understood. The objective of this study was to analyze the effects of a natural cross-linking agent, genipin (GE), on dentin discoloration, collagen stability, and changes in amino acid composition and lysyl oxidase mediated natural collagen cross-links. Dentin collagen obtained from extracted bovine teeth was treated with three different concentrations of GE (0.01%, 0.1%, and 0.5%) for several treatment times (0–24 h). Changes in biochemical properties of NaB3H4-reduced collagen were characterized by amino acid and cross-link analyses. The treatment of dentin collagen with GE resulted in a concentration- and time-dependent pigmentation and stability against bacterial collagenase. The lysyl oxidase-mediated trivalent mature cross-link, pyridinoline, showed no difference among all groups while the major divalent immature cross-link, dehydro-dihydroxylysinonorleucine/its ketoamine in collagen treated with 0.5% GE for 24 h, significantly decreased compared to control (). The newly formed GE-induced cross-links most likely involve lysine and hydroxylysine residues of collagen in a concentration-dependent manner. Some of these cross-links appear to be reducible and stabilized with NaB3H4. Hiroko Nagaoka, Hideaki Nagaoka, Ricardo Walter, Lee W. Boushell, Patricia A. Miguez, Andrew Burton, André V. Ritter, and Mitsuo Yamauchi Copyright © 2014 Hiroko Nagaoka et al. All rights reserved. D-Glucosamine Conjugation Accelerates the Labeling Efficiency of Quantum Dots in Osteoblastic Cells Mon, 24 Mar 2014 08:47:48 +0000 Quantum dots (QDs) are useful imaging tools in the medical and biological fields due to their optical properties, such as a high fluorescence intensity, remarkable resistance to photobleaching, broad absorption spectra, and narrow emission spectra. This is the first study to investigate the uptake of carboxylated QDs conjugated with D-glucosamine (core size: approximately 3 nm, final modified size: 20–30 nm) into cultured osteoblastic cells. The QDs attached to the cell surface and were transported into the cytoplasm within approximately three hours of culture, whose process was clearly demonstrated using specific fluorescent staining of the cell membrane. Although the intranuclear distribution was not observed, a dramatic decrease in the transfer of quantum dots into the cytoplasm was recognized after approximately seven days of culture. Other interesting phenomena include the escape of the quantum dots from lysosomes in the cytoplasm, as confirmed by the merging of both QD fluorescence and specific fluorescent staining of lysosomes in the cytoplasm. These findings suggest that D-glucosamine conjugation enhances proton absorption in acid organelles and promotes the lysosomal escape of QDs. Kazunari Igawa, Ming-Fang Xie, Hideki Ohba, Shizuka Yamada, and Yoshihiko Hayashi Copyright © 2014 Kazunari Igawa et al. All rights reserved. Acute and Subacute Toxicity In Vivo of Thermal-Sprayed Silver Containing Hydroxyapatite Coating in Rat Tibia Thu, 20 Mar 2014 09:45:21 +0000 To reduce the incidence of implant-associated infection, we previously developed a novel coating technology using hydroxyapatite (HA) containing silver (Ag). This study examined in vivo acute and subacute toxicity associated with the Ag-HA coating in rat tibiae. Ten-week-old rats received implantation of HA-, 2% Ag-HA-, or 50% Ag-HA-coated titanium rods. Concentrations of silver in serum, brain, liver, kidneys, and spleen were measured in the acute phase (2–4 days after treatment) and subacute phase (4–12 weeks after treatment). Biochemical and histological examinations of those organs were also performed. Mean serum silver concentration peaked in the acute phase and then gradually decreased. Mean silver concentrations in all examined organs from the 2% Ag-HA coating groups showed no significant differences compared with the HA coating group. No significant differences in mean levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, creatinine, or blood urea nitrogen were seen between the three groups and controls. Histological examinations of all organs revealed no abnormal pathologic findings. No acute or subacute toxicity was seen in vivo for 2% Ag-HA coating or HA coating. Ag-HA coatings on implants may represent biologically safe antibacterial biomaterials and may be of value for reducing surgical-site infections related to implantation. Masatsugu Tsukamoto, Hiroshi Miyamoto, Yoshiki Ando, Iwao Noda, Shuichi Eto, Takayuki Akiyama, Yutaka Yonekura, Motoki Sonohata, and Masaaki Mawatari Copyright © 2014 Masatsugu Tsukamoto et al. All rights reserved. Effects of Prepolymerized Particle Size and Polymerization Kinetics on Volumetric Shrinkage of Dental Modeling Resins Mon, 17 Mar 2014 09:25:35 +0000 Dental modeling resins have been developed for use in areas where highly precise resin structures are needed. The manufacturers claim that these polymethyl methacrylate/methyl methacrylate (PMMA/MMA) resins show little or no shrinkage after polymerization. This study examined the polymerization shrinkage of five dental modeling resins as well as one temporary PMMA/MMA resin (control). The morphology and the particle size of the prepolymerized PMMA powders were investigated by scanning electron microscopy and laser diffraction particle size analysis, respectively. Linear polymerization shrinkage strains of the resins were monitored for 20 minutes using a custom-made linometer, and the final values (at 20 minutes) were converted into volumetric shrinkages. The final volumetric shrinkage values for the modeling resins were statistically similar () or significantly larger () than that of the control resin and were related to the polymerization kinetics () rather than the PMMA bead size (). Therefore, the optimal control of the polymerization kinetics seems to be more important for producing high-precision resin structures rather than the use of dental modeling resins. Tae-Yub Kwon, Jung-Yun Ha, Ju-Na Chun, Jun Sik Son, and Kyo-Han Kim Copyright © 2014 Tae-Yub Kwon et al. All rights reserved. A Proteomic View to Characterize the Effect of Chitosan Nanoparticle to Hepatic Cells: Is Chitosan Nanoparticle an Enhancer of PI3K/AKT1/mTOR Pathway? Sun, 16 Mar 2014 12:37:43 +0000 Chitosan nanoparticle, a biocompatible material, was used as a potential drug delivery system widely. Our current investigation studies were the bioeffects of the chitosan nanoparticle uptake by liver cells. In this experiment, the characterizations of chitosan nanoparticles were measured by transmission electron microscopy and particle size analyzer. The average size of the chitosan nanoparticle was  nm, and the average zeta potential was  mV. Moreover, using proteomic approaches to analyze the differential protein expression patterns resulted from the chitosan nanoparticle uptaken by HepG2 and CCL-13 cells identified several proteins involved in the PI3K/AKT1/mTOR pathway. Our experimental results have demonstrated that the chitosan nanoparticle may involve in the liver cancer cell metastasis and proliferation. Ming-Hui Yang, Shyng-Shiou Yuan, Ying-Fong Huang, Po-Chiao Lin, Chi-Yu Lu, Tze-Wen Chung, and Yu-Chang Tyan Copyright © 2014 Ming-Hui Yang et al. All rights reserved. Anti-CD133 Antibody Immobilized on the Surface of Stents Enhances Endothelialization Mon, 10 Mar 2014 09:47:28 +0000 Drug eluting stents successfully reduce restenosis at the cost of delayed reendothelialization. In recent years, a novel concept to enhance reendothelialization using anti-CD34 antibody coated stents which capture circulating progenitor cells (EPCs) has been developed with conflicting clinical results. CD133 is a glycoprotein expressed on circulating hematopoietic and putative endothelial-regenerating cells and may be superior to CD34 for EPCs capture stents. In the present study, anti-CD133 antibody has been successfully immobilized to the biodegradable polymeric coating material by covalent conjugation. We explore whether anti-CD133 antibody coated stents (CD133 stents) might accelerate reendothelialization in comparison with bare metal stents (BMS) through the superior ability to capture EPCs. The in vitro cell culture results indicate that anti-CD133 antibody functionalized polymer film significantly promotes CD133 positive cells attachment and growth compared with the unfunctionalized polymer film. In the semi-in vivo arteriovenous shunt model CD133 stents demonstrate much quicker specific capturing of EPCs from the blood stream than BMS within 6 hours. In a porcine coronary artery injury model CD133 stents show more effective reendothelialization in short term compared with BMS, while no significant difference in endothelial function recovery was observed between these two groups within 6-month followup. Jian Li, Dan Li, Feirong Gong, Shaoyan Jiang, Hua Yu, and Yi An Copyright © 2014 Jian Li et al. All rights reserved. Physical Properties of Polyamide-12 versus PMMA Denture Base Material Sun, 09 Mar 2014 08:03:29 +0000 Objectives. Polyamide-12 (PA) is a flexible material suited for denture bases and clasping. This study investigated its potential aging effects with a focus on surface roughness, color stability, and elasticity. Methods. PA specimens (Valplast) of  mm and equally measuring PMMA specimens (Palapress) as control were fabricated. Color changes after storage in air, water, coffee, and red wine were measured using the CIE color specification. Elasticity after thermocycling (1000, 3000, and 7000 cycles,  ) was measured by three-point bending testing. Mean surface roughness (Ra) was determined after storage in the liquids mentioned above and thermocycling . Results. Tukey’s HSD test revealed statistically significant color changes of PA in red wine ( after 12 days, after 12 days) and coffee ( after 36 days) but no color changes in PMMA. Elastic modulus of PA was 845 MPa and not affected by thermocycling (Tukey's HSD test,  ). Dry specimens showed significantly decreased elasticity . Mean surface roughness (PA 0.20 μm, PMMA 0.28 μm) did not change significantly after thermocycling or storage (Mann-Whitney -test,  ). Significance. PA exhibited a higher susceptibility to discoloration than PMMA. Neither surface roughness nor elasticity of PA was altered by artificial aging. Mieszko Wieckiewicz, Volker Opitz, Gert Richter, and Klaus W. Boening Copyright © 2014 Mieszko Wieckiewicz et al. All rights reserved. Osteoblasts Growth Behaviour on Bio-Based Calcium Carbonate Aragonite Nanocrystal Thu, 06 Mar 2014 06:06:50 +0000 Calcium carbonate (CaCO3) nanocrystals derived from cockle shells emerge to present a good concert in bone tissue engineering because of their potential to mimic the composition, structure, and properties of native bone. The aim of this study was to evaluate the biological response of CaCO3 nanocrystals on hFOB 1.19 and MC3T3 E-1 osteoblast cells in vitro. Cell viability and proliferation were assessed by MTT and BrdU assays, and LDH was measured to determine the effect of CaCO3 nanocrystals on cell membrane integrity. Cellular morphology was examined by SEM and fluorescence microscopy. The results showed that CaCO3 nanocrystals had no toxic effects to some extent. Cell proliferation, alkaline phosphatase activity, and protein synthesis were enhanced by the nanocrystals when compared to the control. Cellular interactions were improved, as indicated by SEM and fluorescent microscopy. The production of VEGF and TGF-1 was also affected by the CaCO3 nanocrystals. Therefore, bio-based CaCO3 nanocrystals were shown to stimulate osteoblast differentiation and improve the osteointegration process. Abdullahi Shafiu Kamba and Zuki Abu Bakar Zakaria Copyright © 2014 Abdullahi Shafiu Kamba and Zuki Abu Bakar Zakaria. All rights reserved. Characterization of Multiwalled Carbon Nanotube-Reinforced Hydroxyapatite Composites Consolidated by Spark Plasma Sintering Tue, 04 Mar 2014 12:09:07 +0000 Pure HA and 1, 3, 5, and 10 vol% multiwalled carbon nanotube- (MWNT-) reinforced hydroxyapatite (HA) were consolidated using a spark plasma sintering (SPS) technique. The relative density of pure HA increased with increasing sintering temperature, but that of the MWNT/HA composite reached almost full density at 900°C, and then decreased with further increases in sintering temperature. The relative density of the MWNT/HA composites increased with increasing MWNT content due to the excellent thermal conductivity of MWNTs. The grain size of MWNT/HA composites decreased with increasing MWNT content and increased with increasing sintering temperature. Pull-out toughening of the MWNTs of the MWNT/HA composites was observed in the fractured surface, which can be used to predict the improvement of the mechanical properties. On the other hand, the existence of undispersed or agglomerate MWNTs in the MWNT/HA composites accompanied large pores. The formation of large pores increased with increasing sintering temperature and MWNT content. The addition of MWNT in HA increased the hardness and fracture toughness by approximately 3~4 times, despite the presence of large pores produced by un-dispersed MWNTs. This provides strong evidence as to why the MWNTs are good candidates as reinforcements for strengthening the ceramic matrix. The MWNT/HA composites did not decompose during SPS sintering. The MWNT-reinforced HA composites were non-toxic and showed a good cell affinity and morphology in vitro for 1 day. Duk-Yeon Kim, Young-Hwan Han, Jun Hee Lee, Inn-Kyu Kang, Byung-Koog Jang, and Sukyoung Kim Copyright © 2014 Duk-Yeon Kim et al. All rights reserved. Chitooligosaccharide and Its Derivatives: Preparation and Biological Applications Mon, 03 Mar 2014 07:39:53 +0000 Chitin is a natural polysaccharide of major importance. This biopolymer is synthesized by an enormous number of living organisms; considering the amount of chitin produced annually in the world, it is the most abundant polymer after cellulose. The most important derivative of chitin is chitosan, obtained by partial deacetylation of chitin under alkaline conditions or by enzymatic hydrolysis. Chitin and chitosan are known to have important functional activities but poor solubility makes them difficult to use in food and biomedicinal applications. Chitooligosaccharides (COS) are the degraded products of chitosan or chitin prepared by enzymatic or chemical hydrolysis of chitosan. The greater solubility and low viscosity of COS have attracted the interest of many researchers to utilize COS and their derivatives for various biomedical applications. In light of the recent interest in the biomedical applications of chitin, chitosan, and their derivatives, this review focuses on the preparation and biological activities of chitin, chitosan, COS, and their derivatives. Gaurav Lodhi, Yon-Suk Kim, Jin-Woo Hwang, Se-Kwon Kim, You-Jin Jeon, Jae-Young Je, Chang-Bum Ahn, Sang-Ho Moon, Byong-Tae Jeon, and Pyo-Jam Park Copyright © 2014 Gaurav Lodhi et al. All rights reserved. Preparation of Cylinder-Shaped Porous Sponges of Poly(L-lactic acid), Poly(DL-lactic-co-glycolic acid), and Poly(-caprolactone) Thu, 27 Feb 2014 09:16:05 +0000 Design of mechanical skeletons of biodegradable synthetic polymers such as poly(L-lactic acid) (PLLA), poly(DL-lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL) is important in the construction of the hybrid scaffolds of biodegradable synthetic polymers and naturally derived polymers such as collagen. In this study, cylinder-shaped PLLA, PLGA, and PCL sponges were prepared by the porogen leaching method using a cylinder model. The effects of polymer type, polymer fraction, cylinder height, pore size, and porosity on the mechanical properties of the cylinder-shape sponges were investigated. SEM observation showed that these cylinder-shaped sponges had evenly distributed bulk pore structures and the wall surfaces were less porous with a smaller pore size than the wall bulk pore structures. The porosity and pore size of the sponges could be controlled by the ratio and size of the porogen materials. The PLGA sponges showed superior mechanical properties than those of the PLLA and PCL sponges. Higher porosity resulted in an inferior mechanical strength. The pore size and sponge height also affected the mechanical properties. The results indicate that cylinder-shaped sponges can be tethered by choosing the appropriate polymers, size and ratio of porogen materials and dimension of sponges based on the purpose of the application. Xiaoming He, Naoki Kawazoe, and Guoping Chen Copyright © 2014 Xiaoming He et al. All rights reserved. Morphological Effects of HA on the Cell Compatibility of Electrospun HA/PLGA Composite Nanofiber Scaffolds Wed, 26 Feb 2014 05:59:58 +0000 Tissue engineering is faced with an uphill challenge to design a platform with appropriate topography and suitable surface chemistry, which could encourage desired cellular activities and guide bone tissue regeneration. To develop such scaffolds, composite nanofiber scaffolds of nHA and sHA with PLGA were fabricated using electrospinning technique. nHA was synthesized using precipitation method, whereas sHA was purchased. The nHA and sHA were suspended in PLGA solution separately and electrospun at optimized electrospinning parameters. The composite nanofiber scaffolds were characterized by FE-SEM, EDX analysis, TEM, XRD analysis, FTIR, and X-ray photoelectron. The potential of the HA/PLGA composite nanofiber as bone scaffolds in terms of their bioactivity and biocompatibility was assessed by culturing the osteoblastic cells onto the composite nanofiber scaffolds. The results from in vitro studies revealed that the nHA/PLGA composite nanofiber scaffolds showed higher cellular adhesion, proliferation, and enhanced osteogenesis performance, along with increased Ca+2 ions release compared to the sHA/PLGA composite nanofiber scaffolds and pristine PLGA nanofiber scaffold. The results show that the structural dependent property of HA might affect its potential as bone scaffold and implantable materials in regenerative medicine and clinical tissue engineering. Adnan Haider, Kailash Chandra Gupta, and Inn-Kyu Kang Copyright © 2014 Adnan Haider et al. All rights reserved. Collagen Scaffolds with Controlled Insulin Release and Controlled Pore Structure for Cartilage Tissue Engineering Tue, 25 Feb 2014 10:38:47 +0000 Controlled and local release of growth factors and nutrients from porous scaffolds is important for maintenance of cell survival, proliferation, and promotion of tissue regeneration. The purpose of the present research was to design a controlled release porous collagen-microbead hybrid scaffold with controlled pore structure capable of releasing insulin for application to cartilage tissue regeneration. Collagen-microbead hybrid scaffold was prepared by hybridization of insulin loaded PLGA microbeads with collagen using a freeze-drying technique. The pore structure of the hybrid scaffold was controlled by using preprepared ice particulates having a diameter range of 150–250 μm. Hybrid scaffold had a controlled pore structure with pore size equivalent to ice particulates and good interconnection. The microbeads showed an even spatial distribution throughout the pore walls. In vitro insulin release profile from the hybrid scaffold exhibited a zero order release kinetics up to a period of 4 weeks without initial burst release. Culture of bovine articular chondrocytes in the hybrid scaffold demonstrated high bioactivity of the released insulin. The hybrid scaffold facilitated cell seeding and spatial cell distribution and promoted cell proliferation. Himansu Sekhar Nanda, Shangwu Chen, Qin Zhang, Naoki Kawazoe, and Guoping Chen Copyright © 2014 Himansu Sekhar Nanda et al. All rights reserved. Carbon Nanotubes Reinforced Composites for Biomedical Applications Mon, 24 Feb 2014 08:37:22 +0000 This review paper reported carbon nanotubes reinforced composites for biomedical applications. Several studies have found enhancement in the mechanical properties of CNTs-based reinforced composites by the addition of CNTs. CNTs reinforced composites have been intensively investigated for many aspects of life, especially being made for biomedical applications. The review introduced fabrication of CNTs reinforced composites (CNTs reinforced metal matrix composites, CNTs reinforced polymer matrix composites, and CNTs reinforced ceramic matrix composites), their mechanical properties, cell experiments in vitro, and biocompatibility tests in vivo. Wei Wang, Yuhe Zhu, Susan Liao, and Jiajia Li Copyright © 2014 Wei Wang et al. All rights reserved. Impact of Core-Forming Segment Structure on Drug Loading in Biodegradable Polymeric Micelles Using PEG-b-Poly(lactide-co-depsipeptide) Block Copolymers Thu, 20 Feb 2014 16:22:47 +0000 We synthesized series of amphiphilic AB-type block copolymers having systematic variation in the core-forming segments using poly(lactide-co-depsipeptide)s as a hydrophobic segment and prepared polymeric micelles using the block copolymers, PEG-b-poly(lactide-co-depsipeptide). We then discussed the relationship between the core-forming segment structure and drug loading efficiency for the polymeric micelles. PEG-b-poly(lactide-co-depsipeptide)s, PEG-b-PLGL containing l-leucine (Leu), and PEG-b-PLGF containing l-phenylalanine (Phe), with similar molecular weights and various mole fractions of depsipeptide units, were synthesized. Polymeric micelles entrapping model drug (fluorescein, FL) were prepared using these copolymers. As a result, PEG-b-poly(lactide-co-depsipeptide) micelles showed higher drug loading compared with PEG-b-PLLA and PEG-b-PDLLA as controls. The drug loading increased with increase in the mole fraction of depsipeptide unit in the hydrophobic segments. The introduction of aliphatic and aromatic depsipeptide units was effective to achieve higher FL loading into the micelles. PEG-b-PLGL micelle showed higher drug loading than PEG-b-PLGF micelle when the amount of FL in feed was high. These results obtained in this study should be useful for strategic design of polymeric micelle-type drug delivery carrier with high drug loading efficiency. Akihiro Takahashi, Yuta Ozaki, Akinori Kuzuya, and Yuichi Ohya Copyright © 2014 Akihiro Takahashi et al. All rights reserved. Fabrication and Characterization of Thermoresponsive Polystyrene Nanofibrous Mats for Cultured Cell Recovery Thu, 20 Feb 2014 06:21:39 +0000 Rapid cell growth and rapid recovery of intact cultured cells are an invaluable technique to maintain the biological functions and viability of cells. To achieve this goal, thermoresponsive polystyrene (PS) nanofibrous mat was fabricated by electrospinning of PS solution, followed by the graft polymerization of thermoresponsive poly(N-isopropylacrylamide)(PIPAAm) on PS nanofibrous mats. Image analysis of the PS nanofiber revealed a unimodal distribution pattern with 400 nm average fiber diameter. Graft polymerization of PIPAAm on PS nanofibrous mats was confirmed by spectroscopic methods such as ATR-FTIR, ESCA, and AFM. Human fibroblasts were cultured on four different surfaces, PIPAAm-grafted and ungrafted PS dishes and PIPAAm-grafted and ungrafted PS nanofibrous mats, respectively. Cells on PIPAAm-grafted PS nanofibrous mats were well attached, spread, and proliferated significantly much more than those on other surfaces. Cultured cells were easily detached from the PIPAAm-grafted surfaces by decreasing culture temperature to 20°C, while negligible cells were detached from ungrafted surfaces. Moreover, cells on PIPAAm-grafted PS nanofibrous mats were detached more rapidly than those on PIPAAm-grafted PS dishes. These results suggest that thermoresponsive nanofibrous mats are attractive cell culture substrates which enable rapid cell growth and recovery from the culture surface for application to tissue engineering and regenerative medicine. Hwan Hee Oh, Young-Gwang Ko, Hiroshi Uyama, Won Ho Park, Donghwan Cho, and Oh Hyeong Kwon Copyright © 2014 Hwan Hee Oh et al. All rights reserved. Targeted Delivery System of Nanobiomaterials in Anticancer Therapy: From Cells to Clinics Wed, 19 Feb 2014 13:42:10 +0000 Targeted delivery systems of nanobiomaterials are necessary to be developed for the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to recognize cancer-specific receptors at the cellular levels and to deliver anticancer drugs into the diseased sites. In particular, nanobiomaterial-based nanocarriers, so-called nanoplatforms, are the design of the targeted delivery systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates, norganic materials, carbon-based nanobiomaterials, and bioinspired phage system, which are based on the nanosize of 1–100 nm in diameter. In this review, the design and the application of these nanoplatforms are discussed at the cellular levels as well as in the clinics. We believe that this review can offer recent advances in the targeted delivery systems of nanobiomaterials regarding in vitro and in vivo applications and the translation of nanobiomaterials to nanomedicine in anticancer therapy. Su-Eon Jin, Hyo-Eon Jin, and Soon-Sun Hong Copyright © 2014 Su-Eon Jin et al. All rights reserved. Hydrocolloid-Stabilized Magnetite for Efficient Removal of Radioactive Phosphates Tue, 18 Feb 2014 14:01:07 +0000 Liquid radioactive waste is a common by-product when using radioactive isotopes in research and medicine. Efficient remediation of such liquid waste is crucial for increasing safety during the necessary storage of the material. Herein, we present a novel Gum Karaya stabilized magnetite for the efficient removal of radioactive phosphorus 32P from liquid radioactive waste. This environmentally friendly material is well suited to be used as a nanohydrogel for the removal of liquid waste, which can then be stored in a smaller space and without the risk of the spills inherent to the initial liquid material. The maximum adsorption capacity of the GK/M in this study was found to be 15.68 GBq/g. We present a thorough morphological characterization of the synthesised GK/M, as well as a discussion of the possible phosphorus adsorption mechanisms. Vinod Vellora Thekkae Padil, Michael Rouha, and Miroslav Černík Copyright © 2014 Vinod Vellora Thekkae Padil et al. All rights reserved. Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications Thu, 13 Feb 2014 09:17:08 +0000 Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction. Fatemeh Ajalloueian, Hossein Tavanai, Jöns Hilborn, Olivier Donzel-Gargand, Klaus Leifer, Abeni Wickham, and Ayyoob Arpanaei Copyright © 2014 Fatemeh Ajalloueian et al. All rights reserved. Effects of Dental Methacrylates on Oxygen Consumption and Redox Status of Human Pulp Cells Wed, 12 Feb 2014 13:35:26 +0000 Several studies have already demonstrated that the incomplete polymerization of resin-based dental materials causes the release of monomers which might affect cell metabolism. The aim of this study was to investigate the effects of triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, urethane dimethacrylate, and 2-hydroxyethyl methacrylate on (1) cellular energy metabolism, evaluating oxygen consumption rate, glucose consumption, glucose 6-phosphate dehydrogenase activity, and lactate production, and (2) cellular redox status, through the evaluation of glutathione concentration and of the activities of enzymes regulating glutathione metabolism. Methods. Human pulp cells were used and oxygen consumption was measured by means of a Clark electrode. Moreover, reactive oxygen species production was quantified. Enzymatic activity and glucose and lactate concentrations were determined through a specific kit. Results. Triethylene glycol dimethacrylate, 1,4-butanediol dimethacrylate, and 2-hydroxyethyl methacrylate induced a decrease in oxygen consumption rate, an enhancement of glucose consumption, and lactate production, whilst glucose 6-phosphate dehydrogenase and glutathione reductase activity were not significantly modified. Moreover, the monomers induced an increase of reactive oxygen species production with a consequent increase of superoxide dismutase and catalase enzymatic activities. A depletion of both reduced and total glutathione was also observed. Conclusion. The obtained results indicate that dental monomers might alter energy metabolism and glutathione redox balance in human pulp cells. Giuseppina Nocca, Cinzia Callà, Giuseppe Ettore Martorana, Loredana Cicillini, Sandro Rengo, Alessandro Lupi, Massimo Cordaro, Maria Luisa Gozzo, and Gianrico Spagnuolo Copyright © 2014 Giuseppina Nocca et al. All rights reserved. Comparative Biomechanical and Microstructural Analysis of Native versus Peracetic Acid-Ethanol Treated Cancellous Bone Graft Tue, 11 Feb 2014 16:06:43 +0000 Bone transplantation is frequently used for the treatment of large osseous defects. The availability of autologous bone grafts as the current biological gold standard is limited and there is a risk of donor site morbidity. Allogenic bone grafts are an appealing alternative, but disinfection should be considered to reduce transmission of infection disorders. Peracetic acid-ethanol (PE) treatment has been proven reliable and effective for disinfection of human bone allografts. The purpose of this study was to evaluate the effects of PE treatment on the biomechanical properties and microstructure of cancellous bone grafts (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at −20°C and subjected to compression testing and histological and scanning electron microscopy (SEM) analysis. The levels of compressive strength, stiffness (Young’s modulus), and fracture energy were significantly decreased upon PE treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG demonstrated a 42% increase in ultimate strain. SEM revealed a modified microstructure of CBG with an exposed collagen fiber network after PE treatment. We conclude that the observed reduced compressive strength and reduced stiffness may be beneficial during tissue remodeling thereby explaining the excellent clinical performance of PE-treated CBG. Juliane Rauh, Florian Despang, Jorgen Baas, Cornelia Liebers, Axel Pruss, Michael Gelinsky, Klaus-Peter Günther, and Maik Stiehler Copyright © 2014 Juliane Rauh et al. All rights reserved. D-Glucosamine Promotes Transfection Efficiency during Electroporation Tue, 11 Feb 2014 11:29:37 +0000 D-Glucosamine is a useful medicament in various fields of medicine and dentistry. With respect to stability of the cell membrane, it has been reported that bradykinin-induced nociceptive responses are significantly suppressed by the direct application of D-glucosamine. Electroporation is usually used to effectively introduce foreign genes into tissue culture cells. Buffers for electroporation with or without D-glucosamine are used in experiments of transfection vectors. This is the first study to indirectly observe the stability and protection of the osteoblast membrane against both electric stress and gene uptake (the proton sponge hypothesis: osmotic rupture during endosomes prior to fusion with lysosomes) in electroporation with D-glucosamine application. The transfection efficiency was evaluated as the fluorescence intensity of the transfected green fluorescent protein (GFP) in the cultured cells (osteoblasts; NOS-1 cells). The transfection efficiency increased over 30% in the electroporation samples treated with D-glucosamine-supplemented buffer after one day. The membrane absorption of D-glucosamine is the primary mechanism of membrane stress induced by electric stress. This new function of D-glucosamine is useful and meaningful for developing more effective transformation procedures. Kazunari Igawa, Naoko Ohara, Atsushi Kawakubo, Kouji Sugimoto, Kajiro Yanagiguchi, Takeshi Ikeda, Shizuka Yamada, and Yoshihiko Hayashi Copyright © 2014 Kazunari Igawa et al. All rights reserved. Chitosan Feasibility to Retain Retinal Stem Cell Phenotype and Slow Proliferation for Retinal Transplantation Sun, 02 Feb 2014 09:03:37 +0000 Retinal stem cells (RSCs) are promising in cell replacement strategies for retinal diseases. RSCs can migrate, differentiate, and integrate into retina. However, RSCs transplantation needs an adequate support; chitosan membrane (ChM) could be one, which can carry RSCs with high feasibility to support their integration into retina. RSCs were isolated, evaluated for phenotype, and subsequently grown on sterilized ChM and polystyrene surface for 8 hours, 1, 4, and 11 days for analysing cell adhesion, proliferation, viability, and phenotype. Isolated RSCs expressed GFAP, PKC, isolectin, recoverin, RPE65, PAX-6, cytokeratin 8/18, and nestin proteins. They adhered (28 ± 16%, 8 hours) and proliferated (40 ± 20 cells/field, day 1 and 244 ± 100 cells/field, day 4) significantly low on ChM. However, they maintained similar viability (>95%) and phenotype (cytokeratin 8/18, PAX6, and nestin proteins expression, day 11) on both surfaces (ChM and polystyrene). RSCs did not express alpha-SMA protein on both surfaces. RSCs express proteins belonging to epithelial, glial, and neural cells, confirming that they need further stimulus to reach a final destination of differentiation that could be provided in in vivo condition. ChM does not alternate RSCs behaviour and therefore can be used as a cell carrier so that slow proliferating RSCs can migrate and integrate into retina. Girish K. Srivastava, David Rodriguez-Crespo, Amar K. Singh, Clara Casado-Coterillo, Ivan Fernandez-Bueno, Maria T. Garcia-Gutierrez, Joaquin Coronas, and J. Carlos Pastor Copyright © 2014 Girish K. Srivastava et al. All rights reserved. Enhanced Neural Cell Adhesion and Neurite Outgrowth on Graphene-Based Biomimetic Substrates Thu, 30 Jan 2014 09:30:30 +0000 Neural cell adhesion and neurite outgrowth were examined on graphene-based biomimetic substrates. The biocompatibility of carbon nanomaterials such as graphene and carbon nanotubes (CNTs), that is, single-walled and multiwalled CNTs, against pheochromocytoma-derived PC-12 neural cells was also evaluated by quantifying metabolic activity (with WST-8 assay), intracellular oxidative stress (with ROS assay), and membrane integrity (with LDH assay). Graphene films were grown by using chemical vapor deposition and were then coated onto glass coverslips by using the scooping method. Graphene sheets were patterned on SiO2/Si substrates by using photolithography and were then covered with serum for a neural cell culture. Both types of CNTs induced significant dose-dependent decreases in the viability of PC-12 cells, whereas graphene exerted adverse effects on the neural cells just at over 62.5 ppm. This result implies that graphene and CNTs, even though they were the same carbon-based nanomaterials, show differential influences on neural cells. Furthermore, graphene-coated or graphene-patterned substrates were shown to substantially enhance the adhesion and neurite outgrowth of PC-12 cells. These results suggest that graphene-based substrates as biomimetic cues have good biocompatibility as well as a unique surface property that can enhance the neural cells, which would open up enormous opportunities in neural regeneration and nanomedicine. Suck Won Hong, Jong Ho Lee, Seok Hee Kang, Eun Young Hwang, Yu-Shik Hwang, Mi Hee Lee, Dong-Wook Han, and Jong-Chul Park Copyright © 2014 Suck Won Hong et al. All rights reserved. Electrochemical Impedance Spectroscopy Investigation on the Clinical Lifetime of ProTaper Rotary File System Wed, 29 Jan 2014 13:17:12 +0000 The main objective of the current paper is to show that electrochemical impedance spectroscopy (EIS) could be a method for evaluating and predicting of ProTaper rotary file system clinical lifespan. This particular aspect of everyday use of the endodontic files is of great importance in each dental practice and has profound clinical implications. The method used for quantification resides in the electrochemical impedance spectroscopy theory and has in its main focus the characteristics of the surface titanium oxide layer. This electrochemical technique has been adapted successfully to identify the quality of the Ni-Ti files oxide layer. The modification of this protective layer induces changes in corrosion behavior of the alloy modifying the impedance value of the file. In order to assess the method, 14 ProTaper sets utilized on different patients in a dental clinic have been submitted for testing using EIS. The information obtained in regard to the surface oxide layer has offered an indication of use and proves that the said layer evolves with each clinical application. The novelty of this research is related to an electrochemical technique successfully adapted for Ni-Ti file investigation and correlation with surface and clinical aspects. Virgil Penta, Cristian Pirvu, and Ioana Demetrescu Copyright © 2014 Virgil Penta et al. All rights reserved. Specific Intracellular Uptake of Herceptin-Conjugated CdSe/ZnS Quantum Dots into Breast Cancer Cells Thu, 09 Jan 2014 13:28:22 +0000 Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). The mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. The in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. To clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined by confocal laser scanning microscopy. As a result, the QD-Her bound specifically to the membrane of SK-BR3, which became almost saturated after 6 hours incubation. This suggests that the growth signal of breast cancer cells is inhibited completely by the specific binding of herceptin to the Her-2 receptor of SK-BR3 membrane, resulting in cell death. Seung-Jin Han, Pierson Rathinaraj, Soo-Young Park, Young Kyoo Kim, Joon Hyung Lee, Inn-Kyu Kang, Jong-Sik Moon, and Jeffrey G. Winiarz Copyright © 2014 Seung-Jin Han et al. All rights reserved. The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization Mon, 30 Dec 2013 16:22:32 +0000 To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function. Hongyang Gao, Yang You, Guoping Zhang, Feng Zhao, Ziyi Sha, and Yong Shen Copyright © 2013 Hongyang Gao et al. All rights reserved. Immobilization of Bone Morphogenetic Protein on DOPA- or Dopamine-Treated Titanium Surfaces to Enhance Osseointegration Sat, 28 Dec 2013 19:09:58 +0000 Titanium was treated with 3,4-dihydroxy-L-phenylalanine (DOPA) or dopamine to immobilize bone morphogenetic protein-2 (BMP2), a biomolecule. DOPA and dopamine solutions turned into suspensions, and precipitates were produced at high pH. Both treatments produced a brown surface on titanium that was thicker at high pH than low pH. Dopamine produced a thicker layer than DOPA. The hydrophobicity of the surfaces increased after treatment with dopamine independent of pH. Furthermore, there were more amino groups in the layers formed at pH 8.5 than pH 4.5 in both treatments. Dopamine treatment produced more amino groups in the layer than DOPA. BMP2 was immobilized on the treated surfaces via a coupling reaction using carbodiimide. More BMP2 was immobilized on surfaces treated at pH 8.5 than pH 4.5 in both treatments. The immobilized BMP induced specific signal transduction and alkali phosphatase, a differentiation marker. Thus, the present study demonstrates that titanium treated with DOPA or dopamine can become bioactive via the surface immobilization of BMP2, which induces specific signal transduction. Jeonghwa Kang, Seiichi Tada, Takashi Kitajima, Tae Il Son, Toshiro Aigaki, and Yoshihiro Ito Copyright © 2013 Jeonghwa Kang et al. All rights reserved. Biodistribution and Molecular Studies on Orally Administered Nanoparticle-AON Complexes Encapsulated with Alginate Aiming at Inducing Dystrophin Rescue in mdx Mice Thu, 12 Dec 2013 18:06:35 +0000 We have previously demonstrated that intraperitoneal injections of 2′-O-methyl-phosphorothioate (2′OMePS) antisense oligoribonucleotides adsorbed onto a cationic core-shell nanoparticles (NPs), termed ZM2, provoke dystrophin restoration in the muscles of mdx mice. The aim of the present work was to evaluate the oral route as an alternative way of administration for ZM2-antisense oligoribonucleotides complexes. The biodistribution and elimination of nanoparticles were evaluated after single and multiple oral doses of IR-dye conjugated nanoparticles. Labeled nanoparticles were tracked in vivo as well as in tissue cryosections, urines and feces by Odyssey infrared imaging system, and revealed a permanence in the intestine and abdominal lymph nodes for 72 hours to 7 days before being eliminated. We subsequently tested alginate-free and alginate-encapsulated ZM2-antisense oligoribonucleotides (AON) complexes orally administered 2 and 3 times per week, respectively, in mdx mice for a total of 12 weeks. Treatment with alginate ZM2-AON induced a slight dystrophin rescue in diaphragm and intestine smooth muscles, while no dystrophin was detected in alginate-free ZM2-AON treated mice. These data encourage further experiments on oral administration testing of NP and AON complexes, possibly translatable in oligoribonucleotides-mediated molecular therapies. Maria Sofia Falzarano, Chiara Passarelli, Elena Bassi, Marina Fabris, Daniela Perrone, Patrizia Sabatelli, Nadir M. Maraldi, Silvia Donà, Rita Selvatici, Paolo Bonaldo, Katia Sparnacci, Michele Laus, Paola Braghetta, Paola Rimessi, and Alessandra Ferlini Copyright © 2013 Maria Sofia Falzarano et al. All rights reserved. The Application of Fiber-Reinforced Materials in Disc Repair Sun, 08 Dec 2013 13:27:58 +0000 The intervertebral disc degeneration and injury are the most common spinal diseases with tremendous financial and social implications. Regenerative therapies for disc repair are promising treatments. Fiber-reinforced materials (FRMs) are a kind of composites by embedding the fibers into the matrix materials. FRMs can maintain the original properties of the matrix and enhance the mechanical properties. By now, there are still some problems for disc repair such as the unsatisfied static strength and dynamic properties for disc implants. The application of FRMs may resolve these problems to some extent. In this review, six parts such as background of FRMs in tissue repair, the comparison of mechanical properties between natural disc and some typical FRMs, the repair standard and FRMs applications in disc repair, and the possible research directions for FRMs' in the future are stated. Bao-Qing Pei, Hui Li, Gang Zhu, De-Yu Li, Yu-Bo Fan, and Shu-Qin Wu Copyright © 2013 Bao-Qing Pei et al. All rights reserved. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer Thu, 05 Dec 2013 16:03:00 +0000 Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA) was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs) coated with oleic acid (OA) were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES). Bovine serum albumin (BSA) was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug. J. Varshosaz, H. Sadeghi-aliabadi, S. Ghasemi, and B. Behdadfar Copyright © 2013 J. Varshosaz et al. All rights reserved. Fabrication of Microfibrous and Nano-/Microfibrous Scaffolds: Melt and Hybrid Electrospinning and Surface Modification of Poly(L-lactic acid) with Plasticizer Thu, 05 Dec 2013 09:18:23 +0000 Biodegradable poly(L-lactic acid) (PLA) fibrous scaffolds were prepared by electrospinning from a PLA melt containing poly(ethylene glycol) (PEG) as a plasticizer to obtain thinner fibers. The effects of PEG on the melt electrospinning of PLA were examined in terms of the melt viscosity and fiber diameter. Among the parameters, the content of PEG had a more significant effect on the average fiber diameter and its distribution than those of the spinning temperature. Furthermore, nano-/microfibrous silk fibroin (SF)/PLA and PLA/PLA composite scaffolds were fabricated by hybrid electrospinning, which involved a combination of solution electrospinning and melt electrospinning. The SF/PLA (20/80) scaffolds consisted of a randomly oriented structure of PLA microfibers (average fiber diameter = 8.9 µm) and SF nanofibers (average fiber diameter = 820 nm). The PLA nano-/microfiber (20/80) scaffolds were found to have similar pore parameters to the PLA microfiber scaffolds. The PLA scaffolds were treated with plasma in the presence of either oxygen or ammonia gas to modify the surface of the fibers. This approach of controlling the surface properties and diameter of fibers could be useful in the design and tailoring of novel scaffolds for tissue engineering. Young Il Yoon, Ko Eun Park, Seung Jin Lee, and Won Ho Park Copyright © 2013 Young Il Yoon et al. All rights reserved. Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells Wed, 04 Dec 2013 15:04:27 +0000 The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation. Xinhui Liu, Guoping Zhang, Chuanyong Hou, Hua Wang, Yelin Yang, Guoping Guan, Wei Dong, Hongyang Gao, and Qingling Feng Copyright © 2013 Xinhui Liu et al. All rights reserved. Nano Polymeric Carrier Fabrication Technologies for Advanced Antitumor Therapy Wed, 04 Dec 2013 09:54:35 +0000 Comparing with the traditional therapeutic methods, newly developed cancer therapy based on the nanoparticulates attracted extensively interest due to its unique advantages. However, there are still some drawbacks such as the unfavorable in vivo performance for nanomedicine and undesirable tumor escape from the immunotherapy. While as we know that the in vivo performance strongly depended on the nanocarrier structural properties, thus, the big gap between in vitro and in vivo can be overcome by nanocarrier’s structural tailoring by fine chemical design and microstructural tuning. In addition, this fine nanocarrier’s engineering can also provide practical solution to solve the problems in traditional cancer immunotherapy. In this paper, we review the latest development in nanomedicine, cancer therapy, and nanoimmunotherapy. We then give an explanation why fine nanocanrrie’s engineering with special focus on the unique pathology of tumor microenvironments and properties of immunocells can obviously promote the in vivo performance and improve the therapeutic index of nanoimmunotherapy. Wei Li, Mengxin Zhao, Changhong Ke, Ge Zhang, Li Zhang, Huafei Li, Fulei Zhang, Yun Sun, Jianxin Dai, Hao Wang, and Yajun Guo Copyright © 2013 Wei Li et al. All rights reserved. Synthesis, Characterization, and Acute Oral Toxicity Evaluation of pH-Sensitive Hydrogel Based on MPEG, Poly(ε-caprolactone), and Itaconic Acid Sat, 30 Nov 2013 16:50:56 +0000 A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol)-poly(caprolactone)-acryloyl chloride (MPEG-PCL-AC, PECA), poly(ethylene glycol) methyl ether methacrylate (MPEGMA, MEG), N,N-methylenebisacrylamide (BIS), and itaconic acid (IA) were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by 1H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system. Liwei Tan, Xu Xu, Jia Song, Feng Luo, and Zhiyong Qian Copyright © 2013 Liwei Tan et al. All rights reserved. Carbon Nanotubes: Applications in Pharmacy and Medicine Mon, 30 Sep 2013 13:51:30 +0000 Carbon nanotubes (CNTs) are allotropes of carbon, made of graphite and constructed in cylindrical tubes with nanometer in diameter and several millimeters in length. Their impressive structural, mechanical, and electronic properties are due to their small size and mass, their strong mechanical potency, and their high electrical and thermal conductivity. CNTs have been successfully applied in pharmacy and medicine due to their high surface area that is capable of adsorbing or conjugating with a wide variety of therapeutic and diagnostic agents (drugs, genes, vaccines, antibodies, biosensors, etc.). They have been first proven to be an excellent vehicle for drug delivery directly into cells without metabolism by the body. Then other applications of CNTs have been extensively performed not only for drug and gene therapies but also for tissue regeneration, biosensor diagnosis, enantiomer separation of chiral drugs, extraction and analysis of drugs and pollutants. Moreover, CNTs have been recently revealed as a promising antioxidant. This minireview focuses the applications of CNTs in all fields of pharmacy and medicine from therapeutics to analysis and diagnosis as cited above. It also examines the pharmacokinetics, metabolism and toxicity of different forms of CNTs and discusses the perspectives, the advantages and the obstacles of this promising bionanotechnology in the future. Hua He, Lien Ai Pham-Huy, Pierre Dramou, Deli Xiao, Pengli Zuo, and Chuong Pham-Huy Copyright © 2013 Hua He et al. All rights reserved. Characterization and In Vivo Biological Performance of Biosilicate Wed, 25 Sep 2013 11:18:23 +0000 After an introduction showing the growing interest in glasses and glass-ceramics as biomaterials used for bone healing, we describe a new biomaterial named Biosilicate. Biosilicate is the designation of a group of fully crystallized glass-ceramics of the Na2O-CaO-SiO2-P2O5 system. Several in vitro tests have shown that Biosilicate is a very active biomaterial and that the HCA layer is formed in less than 24 hours of exposure to “simulated body fluid” (SBF) solution. Also, in vitro studies with osteoblastic cells have shown that Biosilicate disks supported significantly larger areas of calcified matrix compared to 45S5 Bioglass, indicating that this bioactive glass-ceramic may promote enhancement of in vitro bone-like tissue formation in osteogenic cell cultures. Finally, due to its special characteristics, Biosilicate has also been successfully tested in several in vivo studies. These studies revealed that the material is biocompatible, presents excellent bioactive properties, and is effective to stimulate the deposition of newly formed bone in animal models. All these data highlight the huge potential of Biosilicate to be used in bone regeneration applications. Ana Claudia M. Renno, Paulo Sérgio Bossini, Murilo C. Crovace, Ana Candida M. Rodrigues, Edgar Dutra Zanotto, and Nivaldo Antonio Parizotto Copyright © 2013 Ana Claudia M. Renno et al. All rights reserved. New Guar Biopolymer Silver Nanocomposites for Wound Healing Applications Mon, 23 Sep 2013 08:31:46 +0000 Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation. Runa Ghosh Auddy, Md Farooque Abdullah, Suvadra Das, Partha Roy, Sriparna Datta, and Arup Mukherjee Copyright © 2013 Runa Ghosh Auddy et al. All rights reserved. Biomaterials-Based Modulation of the Immune System Sun, 22 Sep 2013 10:40:16 +0000 The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, including macrophages, neutrophils, natural killer cells, T-cells, B-cells, and dendritic cells. Most often, these molecular signals lead to the generation of fibrous encapsulation of the biomaterials, thereby shielding the body from these biomaterials. In this review we will focus on two different types of biomaterials: those that actively modulate the immune response, as seen in antigen delivery vehicles for vaccines, and those that illicit relatively small immune response, which are important for implantable materials. The first serves to actively influence the immune response by co-opting certain immune pathways, while the second tries to mimic the properties of the host in an attempt to remain undetected by the immune system. As these are two very different end points, each type of biomaterial has been studied and developed separately and in recent years, many advances have been made in each respective area, which will be highlighted in this review. Austin B. Gardner, Simon K. C. Lee, Elliot C. Woods, and Abhinav P. Acharya Copyright © 2013 Austin B. Gardner et al. All rights reserved. Biomimetic Mineralization on a Macroporous Cellulose-Based Matrix for Bone Regeneration Thu, 19 Sep 2013 08:22:25 +0000 The aim of this study is to investigate the biomimetic mineralization on a cellulose-based porous matrix with an improved biological profile. The cellulose matrix was precalcified using three methods: (i) cellulose samples were treated with a solution of calcium chloride and diammonium hydrogen phosphate; (ii) the carboxymethylated cellulose matrix was stored in a saturated calcium hydroxide solution; (iii) the cellulose matrix was mixed with a calcium silicate solution in order to introduce silanol groups and to combine them with calcium ions. All the methods resulted in a mineralization of the cellulose surfaces after immersion in a simulated body fluid solution. Over a period of 14 days, the matrix was completely covered with hydroxyapatite crystals. Hydroxyapatite formation depended on functional groups on the matrix surface as well as on the precalcification method. The largest hydroxyapatite crystals were obtained on the carboxymethylated cellulose matrix treated with calcium hydroxide solution. The porous cellulose matrix was not cytotoxic, allowing the adhesion and proliferation of human osteoblastic cells. Comparatively, improved cell adhesion and growth rate were achieved on the mineralized cellulose matrices. Odeta Petrauskaite, Pedro de Sousa Gomes, Maria Helena Fernandes, Gintaras Juodzbalys, Arturas Stumbras, Julius Maminskas, Jolanta Liesiene, and Marco Cicciù Copyright © 2013 Odeta Petrauskaite et al. All rights reserved. Preliminary Characterization of Genipin-Cross-Linked Silk Sericin/Poly(vinyl alcohol) Films as Two-Dimensional Wound Dressings for the Healing of Superficial Wounds Wed, 11 Sep 2013 09:47:06 +0000 The genipin-cross-linked silk sericin/poly(vinyl alcohol) (PVA) films were developed aiming to be applied as two-dimensional wound dressings for the treatment of superficial wounds. The effects of genipin cross-linking concentration on the physical and biological properties of the films were investigated. The genipin-cross-linked silk sericin/PVA films showed the increased surface density, tensile strength, and percentage of elongation, but decreased percentage of light transmission, water vapor transmission rate, and water swelling, compared to the non-cross-linked films. This explained that the cross-linking bonds between genipin and silk sericin would reduce the mobility of molecular chains within the films, resulting in the more rigid molecular structure. Silk sericin was released from the genipin-cross-linked films in a sustained manner. In addition, either L929 mouse fibroblast or HaCat keratinocyte cells showed high percentage of viability when cultured on the silk sericin/PVA films cross-linked with 0.075 and 0.1% w/v genipin. The in vivo safety test performed according to ISO 10993-6 confirmed that the genipin-cross-linked silk sericin/PVA films were safe for the medical usages. The efficacy of the films for the treatment of superficial skin wounds will be further investigated in vivo and clinically. The genipin-cross-linked silk sericin/PVA films would be promising choices of two-dimensional wound dressings for the treatment of superficial wounds. Tippawan Siritientong, Juthamas Ratanavaraporn, Teerapol Srichana, and Pornanong Aramwit Copyright © 2013 Tippawan Siritientong et al. All rights reserved. Removal of White Mineral Trioxide Aggregate Cement: A Promising Approach Sun, 08 Sep 2013 16:00:21 +0000 Removal of MTA from dentin by applying 37% hydrochloric acid (HCl) to reduce microhardness and push-out bond strength. Forty dentin slices were filled with WMTA and divided into two groups (). Ten slices remained untreated while others were exposed to either HCl or phosphate buffer saline (PBS) and all samples were subjected to pushout test. The mode of bond failures was determined by SEM analysis. Later, twenty glass tubes were filled with WMTA and divided into two groups (). One side of tube was exposed to HCl or PBS while the other side remained untreated and the microhardness was analyzed by testing machine. HCl showed significantly lower pushout strength and microhardness values (), (). HCl treated samples showed mixed bond failures dominantly, while PBS samples mostly showed adhesive failures. The results of this study can suggest the 37% HCl as an effective solution to aid the removal of MTA from the dentin surfaces. Mohammad Ali Saghiri, Franklin Garcia-Godoy, James L. Gutmann, Nader Sheibani, Armen Asatourian, Mehrdad Lotfi, and Mayam Elyasi Copyright © 2013 Mohammad Ali Saghiri et al. All rights reserved. Biocompatible Bacterial Cellulose-Poly(2-hydroxyethyl methacrylate) Nanocomposite Films Thu, 05 Sep 2013 08:18:35 +0000 A series of bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite films was prepared by in situ radical polymerization of 2-hydroxyethyl methacrylate (HEMA), using variable amounts of poly(ethylene glycol) diacrylate (PEGDA) as cross-linker. Thin films were obtained, and their physical, chemical, thermal, and mechanical properties were evaluated. The films showed improved translucency compared to BC and enhanced thermal stability and mechanical performance when compared to poly(2-hydroxyethyl methacrylate) (PHEMA). Finally, BC/PHEMA nanocomposites proved to be nontoxic to human adipose-derived mesenchymal stem cells (ADSCs) and thus are pointed as potential dry dressings for biomedical applications. Andrea G. P. R. Figueiredo, Ana R. P. Figueiredo, Ana Alonso-Varona, Susana C. M. Fernandes, Teodoro Palomares, Eva Rubio-Azpeitia, Ana Barros-Timmons, Armando J. D. Silvestre, Carlos Pascoal Neto, and Carmen S. R. Freire Copyright © 2013 Andrea G. P. R. Figueiredo et al. All rights reserved. Insight into Biological Apatite: Physiochemical Properties and Preparation Approaches Sun, 01 Sep 2013 15:33:51 +0000 Biological apatite is an inorganic calcium phosphate salt in apatite form and nano size with a biological derivation. It is also the main inorganic component of biological hard tissues such as bones and teeth of vertebrates. Consequently, biological apatite has a wide application in dentistry and orthopedics by using as dental fillers and bone substitutes for bone reconstruction and regeneration. Given this, it is of great significance to obtain a comprehensive understanding of its physiochemical and biological properties. However, upon the previous studies, inconsistent and inadequate data of such basic properties as the morphology, crystal size, chemical compositions, and solubility of biological apatite were reported. This may be ascribed to the differences in the source of raw materials that biological apatite are made from, as well as the effect of the preparation approaches. Hence, this paper is to provide some insights rather than a thorough review of the physiochemical properties as well as the advantages and drawbacks of various preparation methods of biological apatite. Quan Liu, Shishu Huang, Jukka Pekka Matinlinna, Zhuofan Chen, and Haobo Pan Copyright © 2013 Quan Liu et al. All rights reserved. Effect of Cyclic Precalcification of Nanotubular TiO2 Layer on the Bioactivity of Titanium Implant Thu, 29 Aug 2013 11:29:37 +0000 The objective of this study is to investigate the effect of cyclic precalcification treatment to impart bioactive properties for titanium implants. Before precalcification, the titanium implants were subjected to blasting using hydroxyapatite (HAp), a resorbable blasting medium (RBM treated), and anodized using an electrolyte containing glycerol, H2O, and NH4F. Precalcification treatment was performed by two different methods, namely, continuous immersion treatment (CIT) and alternate immersion treatment (AIT). In CIT, the RBM treated and anodized titanium implants were immersed in 0.05 M NaH2PO4 solution at 80°C and saturated Ca(OH)2 solution at 100°C for 20 min, whereas during AIT, they were immersed alternatively in both solutions for 1 min for 20 cycles. Anodizing of the titanium implants enables the formation of self-organized TiO2 nanotubes. Cyclic precalcification treatment imparts a better bioactive property and enables an increase in activation level of the titanium implants. The removal torque values of the RBM treated, CIT treated, and AIT treated titanium implants are  Ncm,  Ncm, and  Ncm, respectively. The findings of the study indicate the cyclic precalcification in an effective surface treatment method that would help accelerate osseointegration and impart bioactive property of titanium implants. Il Song Park, Eun Jin Yang, and Tae Sung Bae Copyright © 2013 Il Song Park et al. All rights reserved. Magnesium Coated Bioresorbable Phosphate Glass Fibres: Investigation of the Interface between Fibre and Polyester Matrices Tue, 27 Aug 2013 14:56:46 +0000 Bioresorbable phosphate glass fibre reinforced polyester composites have been investigated as replacement for some traditional metallic orthopaedic implants, such as bone fracture fixation plates. However, composites tested revealed loss of the interfacial integrity after immersion within aqueous media which resulted in rapid loss of mechanical properties. Physical modification of fibres to change fibre surface morphology has been shown to be an effective method to improve fibre and matrix adhesion in composites. In this study, biodegradable magnesium which would gradually degrade to Mg2+ in the human body was deposited via magnetron sputtering onto bioresorbable phosphate glass fibres to obtain roughened fibre surfaces. Fibre surface morphology after coating was observed using scanning electron microscope (SEM). The roughness profile and crystalline texture of the coatings were determined via atomic force microscope (AFM) and X-ray diffraction (XRD) analysis, respectively. The roughness of the coatings was seen to increase from  nm to  nm. The mechanical properties (tensile strength and modulus) of fibre with coatings decreased with increased magnesium coating thickness. Xiaoling Liu, David M. Grant, Andrew J. Parsons, Lee T. Harper, Chris D. Rudd, and Ifty Ahmed Copyright © 2013 Xiaoling Liu et al. All rights reserved. The Impact of Thermocycling Process on the Dislodgement Force of Different Endodontic Cements Sat, 24 Aug 2013 09:16:32 +0000 To evaluate the effects of thermocycling (500 cycles, 5°C/55°C) on the push-out bond strength of calcium silicate based cements including WMTA, Nano-WMTA, and Bioaggregate to root dentin. Forty-eight dentin slices were prepared and divided into 3 groups () and filled with Angelus WMTA, Nano-WMTA, or Bioaggregate. After incubation, half of the samples were thermocycled while the other half remained untreated. Push-out bond strength was calculated, and the modes of the bond failures were determined by SEM. The highest bond strength was seen in nonthermocycled Nano-WMTA samples and the lowest in thermocycled Bioaggregate samples. The significant differences between nonthermocycled and thermocycled samples were only noticed in WMTA and Nano-WMTA groups (). The mode of failure for thermocycled samples of all three cements was mostly cohesive. Thermocycling process can drastically affect the push-out bond strength of calcium silicate based cements. The intrastructural damages occurred due to the thermal stresses, causing cohesive failures in set materials. Sealing property of endodontic cements which have experienced the thermal stresses can be jeopardized due to occlusal forces happening in furcation cites. Mohammad Ali Saghiri, Armen Asatourian, Franklin Garcia-Godoy, James L. Gutmann, and Nader Sheibani Copyright © 2013 Mohammad Ali Saghiri et al. All rights reserved. Development of Microencapsulation Delivery System for Long-Term Preservation of Probiotics as Biotherapeutics Agent Wed, 21 Aug 2013 12:21:30 +0000 The administration of probiotic bacteria for health benefit has rapidly expanded in recent years, with a global market worth $32.6 billion predicted by 2014. The oral administration of most of the probiotics results in the lack of ability to survive in a high proportion of the harsh conditions of acidity and bile concentration commonly encountered in the gastrointestinal tract of humans. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. Probiotic encapsulation technology has the potential to protect microorganisms and to deliver them into the gut. However, there are still many challenges to overcome with respect to the microencapsulation process and the conditions prevailing in the gut. This review focuses mainly on the methodological approach of probiotic encapsulation including biomaterials selection and choice of appropriate technology in detailed manner. Himanshu K. Solanki, Dipak D. Pawar, Dushyant A. Shah, Vipul D. Prajapati, Girish K. Jani, Akil M. Mulla, and Prachi M. Thakar Copyright © 2013 Himanshu K. Solanki et al. All rights reserved. Optimization of Sulfide/Sulfite Pretreatment of Lignocellulosic Biomass for Lactic Acid Production Tue, 20 Aug 2013 12:05:09 +0000 Potential of sodium sulfide and sodium sulfite, in the presence of sodium hydroxide was investigated to pretreat the corncob (CC), bagasse (BG), water hyacinth and rice husk (RH) for maximum digestibility. Response Surface Methodology was employed for the optimization of pretreatment factors such as temperature, time and concentration of Na2S and Na2SO3, which had high coefficient of determination () along with low probability value (), indicating the reliable predictability of the model. At optimized conditions, Na2S and Na2SO3 remove up to 97% lignin, from WH and RH, along with removal of hemicellulose (up to 93%) during pretreatment providing maximum cellulose, while in BG and CC; 75.0% and 90.0% reduction in lignin and hemicellulose was observed. Saccharification efficiency of RH, WH, BG and CC after treatment with 1.0% Na2S at 130°C for 2.3–3.0 h was 79.40, 85.93, 87.70, and 88.43%, respectively. WH treated with Na2SO3 showed higher hydrolysis yield (86.34%) as compared to Na2S while other biomass substrates showed 2.0–3.0% less yield with Na2SO3. Resulting sugars were evaluated as substrate for lactic acid production, yielding 26.48, 25.36, 31.73, and 30.31 gL−1 of lactic acid with 76.0, 76.0, 86.0, and 83.0% conversion yield from CC, BG, WH, and RH hydrolyzate, respectively. Muhammad Idrees, Ahmad Adnan, and Fahim Ashraf Qureshi Copyright © 2013 Muhammad Idrees et al. All rights reserved. Evaluation of a Thiolated Chitosan Scaffold for Local Delivery of BMP-2 for Osteogenic Differentiation and Ectopic Bone Formation Tue, 20 Aug 2013 08:18:11 +0000 Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy. In-Ho Bae, Byung-Chul Jeong, Min-Suk Kook, Sun-Hun Kim, and Jeong-Tae Koh Copyright © 2013 In-Ho Bae et al. All rights reserved. HTCC-Modified Nanoclay for Tissue Engineering Applications: A Synergistic Cell Growth and Antibacterial Efficiency Mon, 12 Aug 2013 13:21:17 +0000 This paper deals with the synthesis of a biocompatible chitosan ammonium salt N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC) and using it in montmorillonite ion-exchange process. HTCC-modified montmorillonite (Mt) with different chemical ratios was successfully synthesized, and their characteristics have been verified by XRD and FTIR analyses. Produced samples have been evaluated in terms of antibacterial efficiency and biocompatibility (cell culture test). Antibacterial efficiency of synthesized HTCC/Mt samples has been confirmed against both gram negative bacteria (Escherichia coli) and gram positive bacteria (Staphylococcus aureus). The results disclosed that the antibacterial efficiency of HTCC-modified montmorillonite was unexpectedly even more than HTCC. This excellent synergistic effect has been referred to entrapping bacteria between the intercalated structures of HTCC-modified montmorillonite. Then HTCC on clay layers can seriously attack and damage the entrapped bacteria. An extraordinary biocompatibility, cell attachment, and cell growth even more than tissue culture polystyrene (TCPS) have been recorded in the case of this novel kind of modified clay. Due to existing concerns about serious and chronic infections after implant placement, this natural-based bioactive and antibacterial modified clay can be used in electrospun nanofibers and other polymeric implants with promising mechanical properties for tissue engineering applications. Majid Aliabadi, Roya Dastjerdi, and Kourosh Kabiri Copyright © 2013 Majid Aliabadi et al. All rights reserved. Effect of Boron Addition on the Thermal, Degradation, and Cytocompatibility Properties of Phosphate-Based Glasses Wed, 07 Aug 2013 12:47:23 +0000 In this study eight different phosphate-based glass compositions were prepared by melt-quenching: four in the (P2O5)45-(CaO)16--(MgO)24- system and four in the system (P2O5)50-(CaO)16--(MgO)24-, where and 10 mol%. The effect of B2O3 addition on the thermal properties, density, molar volume, dissolution rates, and cytocompatibility were studied for both glass systems. Addition of B2O3 increased the glass transition (), crystallisation (), melting (), Liquidus () and dilatometric softening () temperature and molar volume (). The thermal expansion coefficient (α) and density () were seen to decrease. An assessment of the thermal stability of the glasses was made in terms of their processing window (crystallisation onset, minus glass transition temperature, ), and an increase in the processing window was observed with increasing B2O3 content. Degradation studies of the glasses revealed that the rates decreased with increasing B2O3 content and a decrease in degradation rates was also observed as the P2O5 content reduced from 50 to 45 mol%. MG63 osteoblast-like cells cultured in direct contact with the glass samples for 14 days revealed comparative data to the positive control for the cell metabolic activity, proliferation, ALP activity, and morphology for glasses containing up to 5 mol% of B2O3. Nusrat Sharmin, Muhammad S. Hasan, Andrew J. Parsons, David Furniss, Colin A. Scotchford, Ifty Ahmed, and Chris D. Rudd Copyright © 2013 Nusrat Sharmin et al. All rights reserved. In Vitro and In Vivo Investigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle Wed, 07 Aug 2013 11:52:45 +0000 Delivering growth factors (GFs) at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS) has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading) and release (delivery) mechanism of a model protein, bovine serum albumin (BSA), from AMS was investigated in vitro as well as in vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction. In vitro evaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS) interaction, determination of in vivo protein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET) was used in an exploratory experiment to determine in vivo BSA release profile from AMS. Results suggest stronger in vivo retention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration. Amol Chaudhari, Lieve Vanmellaert, Matthias Bauwens, Peter Vermaelen, Christophe M. Deroose, Ignace Naert, Marcio Vivan Cardoso, Johan A. Martens, and Joke Duyck Copyright © 2013 Amol Chaudhari et al. All rights reserved. Simulated Microgravity Combined with Polyglycolic Acid Scaffold Culture Conditions Improves the Function of Pancreatic Islets Tue, 06 Aug 2013 08:10:14 +0000 The in vitro culture of pancreatic islets reduces their immunogenicity and prolongs their availability for transplantation. Both simulated microgravity (sMG) and a polyglycolic acid scaffold (PGA) are believed to confer advantages to cell culture. Here, we evaluated the effects of sMG combined with a PGA on the viability, insulin-producing activity and morphological alterations of pancreatic islets. Under PGA-sMG conditions, the purity of the islets was ≥85%, and the islets had a higher survival rate and an increased ability to secrete insulin compared with islets cultured alone in the static, sMG, or PGA conditions. In addition, morphological analysis under scanning electron microscopy (SEM) revealed that the PGA-sMG treatment preserved the integral structure of the islets and facilitated islet adhesion to the scaffolds. These results suggest that PGA-sMG coculture has the potential to improve the viability and function of islets in vitro and provides a promising method for islet transplantation. Yimin Song, Zheng Wei, Chun Song, Shanshan Xie, Jinfa Feng, Jiehou Fan, Zengling Zhang, and Yubo Shi Copyright © 2013 Yimin Song et al. All rights reserved. Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System Mon, 05 Aug 2013 08:39:35 +0000 Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs) coated with polyacrylic acid (PAA) as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30 nm exhibit a saturation magnetization of 87 emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24 h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23 hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors. Yue Xu, Yi Lin, Lin Zhuang, Jiong Lin, Jiahong Lv, Qin Huang, and Jiadong Sun Copyright © 2013 Yue Xu et al. All rights reserved.