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Journal of Healthcare Engineering
Volume 2019, Article ID 5340616, 10 pages
Review Article

The Role of 3D Printing in Medical Applications: A State of the Art

1Aid4Med S.r.l., Udine 33100, Italy
2Head 3 Orthopaedic Department, Istituto Auxologico Italiano IRCCS Capitanio Hospital, Milan 20122, Italy
3BEAMS Department, Université Libre de Bruxelles, Bruxelles 1050, Belgium

Correspondence should be addressed to Anna Aimar; moc.dem4dia@ramia.anna

Received 21 December 2018; Accepted 26 February 2019; Published 21 March 2019

Academic Editor: Antonio Gloria

Copyright © 2019 Anna Aimar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Three-dimensional (3D) printing refers to a number of manufacturing technologies that generate a physical model from digital information. Medical 3D printing was once an ambitious pipe dream. However, time and investment made it real. Nowadays, the 3D printing technology represents a big opportunity to help pharmaceutical and medical companies to create more specific drugs, enabling a rapid production of medical implants, and changing the way that doctors and surgeons plan procedures. Patient-specific 3D-printed anatomical models are becoming increasingly useful tools in today’s practice of precision medicine and for personalized treatments. In the future, 3D-printed implantable organs will probably be available, reducing the waiting lists and increasing the number of lives saved. Additive manufacturing for healthcare is still very much a work in progress, but it is already applied in many different ways in medical field that, already reeling under immense pressure with regards to optimal performance and reduced costs, will stand to gain unprecedented benefits from this good-as-gold technology. The goal of this analysis is to demonstrate by a deep research of the 3D-printing applications in medical field the usefulness and drawbacks and how powerful technology it is.

1. Introduction

Among the different manufacturing processes that are currently adopted by the industry, the 3D printing is an additive technique. It is a process through which a three-dimensional solid object, virtually of any shape, is generated starting from a digital model. Medical 3D printing was once an ambitious pipe dream. However, time and investment made it real. Nowadays, the 3D printing technology represents a big opportunity to help pharmaceutical and medical companies to create more specific drugs, enabling a rapid production of medical implants and changing the way that doctors and surgeons plan procedures [1]. This technology has multiple applications, and the fastest growing innovation in the medical field has been represented by the advent of the 3D printing itself [2]. Five technical steps are required to finalize a printed model. They include selecting the anatomical target area, the development of the 3D geometry through the processing of the medical images coming from a CT/MRI scan, the optimization of the file for the physical printing, and the appropriate selection of the 3D printer and materials (Figure 1). This file represents the guidance for the subsequent printing, “slicing” that digital design model into cross sections. That “sliced” design is then sent to a 3D printer, which manufactures the object by starting at the base layer and building a series of layers on top until the object is built using the raw materials that are needed for its composition. A patient-specific model with anatomical fidelity created from imaging dataset is finally obtained.

Figure 1: 3D-printing workflow.

In this way, the 3D printing has the potential to significantly improve the research knowledge and the skills of the new generation of surgeons, the relationship between patient and surgeon [3], increasing the level of understanding of the disease involved, and the patient-specific design of implantable devices and surgical tools [46] and optimize the surgical process and cost [7]. Nowadays, different printing techniques and material are available in order to better reproduce the patient anatomy. Most of the available printing materials are rigid and therefore not optimum for flexibility and elasticity, unlike biological tissue [8]. Therefore, there are nowadays materials able to close the gap between the real anatomy and the reproduced one, especially considering the soft tissue [9, 10]. In this analysis, an overview of the 3D printing application in medical field is presented, highlighting the usefulness and limitations and how it could be useful for surgeons.

2. Additive Manufacturing Technologies

The 3D-printing techniques have grown in the last decades starting from 1986 when the first stereolithographic (SLA) systems were introduced in practice. Seven are the technical processes related to the 3D printing, each of which is represented by one or more commercial technologies, as shown by the ASTM International [11]. All the processes are listed in Table 1 that reported information about the technologies involved, the materials used, and the medical applications related to each process [12]. A comparison among all the seven techniques is proposed in the same table showing the advantages and disadvantages related to all the processes. Each process uses specific materials with specific properties that relate to medical applications, which are also summarized in Table 1. This general information helps the users to better choose the right technology depending on the application needed.

Table 1: Summary of the 3D-printing process and technologies, focus on materials needed and medical applications, and comparison among the 3D-printing technologies.

These technologies and the related advantages enable the researchers to improve existing medical applications that use 3D-printing technology and to explore new ones. The medical goal that has been already reached is significant and exciting, but some of the more revolutionary applications, such as bio/organ printing, require more time to evolve [2].

3. Transformation Process and Materials Used

Materials used in 3D printing are transformed during the production of the specific model by changing their consistency. This process is named cure and can be done in different ways: a melting of a hard filament in order to give the desired form to the model by the material distortion, liquid solidification for the construction of the structure and powder solidification. All these processes require filler or support material in lattice forms avoiding distortion of the model while the material is being cured. The support material can be easily removed by hand with a cutting tool; however, there is the risk to leave impression on the surface requiring an additional polishing in order to obtain a good-quality printing. The risk of damaging the model, losing details, or break the geometry is really high [23].

The correct selection of the material is directly linked to the selection of the 3D-printing process and printer, as well as the requirements of the model. Related to medical application, similarly to other applications, different anatomical structures need different mechanical properties of the materials to fulfill the required performance of the printed object [8]. The main distinction among the different materials that characterize the human body is between rigid and soft materials. Human bones are an example of rigid tissue and ligaments or articular cartilage are examples of soft materials. Bones are the simplest and easiest biological tissue to be produced by 3D printing as the majority of the materials are rigid. The materials used in 3D printing to model the bone structure are for example acrylonitrile butadiene styrene (ABS) [23], powder of plasters [24], and hydroquinone [8].

Relating to soft tissues, deeper research is still needed in order to decrease the gap between a 3D-printed anatomical model and the human structure. Most of the 3D-printing materials present a lack of realism to mimic adequately a soft human biological tissue. Thus, postprocessing may be necessary in order to soften the printed structures. Some examples are given in the reproduction of cartilaginous tissues [25], arteries for practicing valve replacement [26], hepatic segment [27], and hearts [28]. An interesting example is the development of a 3D-printed brain aneurysm using the flexible TangoPlus™ photopolymer [29] that represented a useful tool to plan the operative strategy in order to treat congenital heart disease. Furthermore, some of the materials used are urethane and rubber-like material, mixed with a rigid photopolymer, to reasonably mimic the artery structure due to their Shore value and elastic properties similar to the physiological one [30, 31].

For a promising future, the multimaterial composites seem to represent a good chance for the 3D printing of human tissues since none of the current available material is able to fully mimic elastic and biological tissues. Multimaterial composites may be designed based on the capacity of the selected biological material to replicate the mechanical properties of human tissue [32]. Mechanical testing may represent a necessary tool to analyze the biomechanical response and validate the artificial material.

Moreover, it is also important to mention that 3D printing allows the reproduction of implantable custom device, but still deeper research needs to be done in order to examine the differences between the traditional and additive manufacturing in terms of mechanical and structural properties, especially fatigue limit needs to be examined further [33].

4. Role of 3D Printing in Medical Field

Every year, 3D printing offers more and more applications in the healthcare field helping to save and improve lives in ways never imagined up to now. In fact, the 3D printing has been used in a wide range of healthcare settings including, but not limited to cardiothoracic surgery [34], cardiology [26], gastroenterology [35], neurosurgery [36], oral and maxillofacial surgery [37], ophthalmology [38], otolaryngology [39], orthopaedic surgery [22], plastic surgery [40], podiatry [41], pulmonology [42], radiation oncology [43], transplant surgery [44], urology [45], and vascular surgery [46].

Thanks to the different benefits that this technology could induce in the field, the main direct applications of 3D printing in the medical and clinical field are as follows [47]:(i)Used for personalized presurgical/treatment and for preoperative planning. This will lead to a multistep procedure that, integrating clinical and imaging information, will determine the best therapeutic option. Several studies have demonstrated that patient-specific presurgical planning may potentially reduce time spent in the operating room (OR) and result in fewer complications [48, 49]. Moreover, this may lead to reduced postoperative stays, decreased reintervention rates, and lower healthcare costs. The 3D-printing technology allows to provide to the surgeon a physical 3D model of the desired patient anatomy that could be used to accurately plan the surgical approach along with cross-sectional imaging or, alternatively, modelling custom prosthetics (or surgical tool) based on patient-specific anatomy [5054]. In this way, a better understanding of a complex anatomy unique to each case is allowed [5256]. Furthermore, the 3D printing gives the possibility to choose before the implantation the size of the prostheses components with very high accuracy [5759].(ii)Customize surgical tools and prostheses: the 3D printing can be used to manufacture custom implants or surgical guides and instruments. Therefore, the customization of surgical tools and prostheses means a reduction of cost given by the additive manufacturing technique [5254, 60].(iii)Study of osteoporotic conditions: following a pharmacological treatment, 3D printing is useful in validating the results achieved by the patient. This enables a more accurate estimation of patientʼs bone condition and a better decision on the surgical treatment [15].(iv)Testing different device in specific pathways: a clear example is the reproduction of different vascular patterns to test the effectiveness of a cardiovascular system used to treat peripheral and coronary artery disease [61]. In this way, the 3D printing enables us to quickly produce prototypes of new design concepts or improvements to existing devices.(v)Improving medical education: 3D-printed patient-specific models have demonstrated that they can increase performance and foster rapid learning [62], while significantly ameliorating the knowledge, management, and confidence of the trainees regardless of the area of expertise [8]. The benefits of 3D printing in education are the reproducibility and safety of the 3D-printed model with respect to the cadaver dissection, the possibility to model different physiologic and pathologic anatomy from a huge dataset of images, and the possibility to share 3D models among different institutions, especially with ones that have fewer resources [63]. 3D printers that have the capability to print with different densities and colours can be used to accentuate the anatomical details [64, 65].(vi)Patient education: patient-centered cares makes patient education one of the top priorities for most healthcare providers. However, communicating imaging reports verbally or by showing patients their CT or MRI scans may not be effective; the patients may not fully understand 2D images representation of a 3D anatomy. On the contrary, 3D printing may improve the doctor-patient communication by showing the anatomic model directly [66, 67].(vii)Storage of rare cases for educational purposes: this role is closely linked to the previous one. This allows the generation of a large dataset composed by datasets of patients affected by rare pathologies, allowing the training of surgeons in specific applications [5254].(viii)Improve the forensic practice: in the courtroom, a 3D model could be used to easily demonstrate various anatomic abnormalities that may be difficult to jury members to understand using cross-sectional imaging [68].(ix)Bioprinting: the 3D printing allows also the modelling of implantable tissue. Some examples are the 3D printing of synthetic skin for transplanting to patients, who suffered burn injuries [69]. It may also be used for testing of cosmetic, chemical, and pharmaceutical products. Another example is the replicating of heart valves using a combination of cells and biomaterials to control the valve’s stiffness [26] or the replicating of human ears using molds filled with a gel containing bovine cartilage cells suspended in collagen [70].(x)Personalized drug 3D printing: the 3D printing of drugs consists of the printing out the powdered drug layer to make it dissolve faster than average pills [71]. It allows also personalization of the patient’s needed quantity [2].(xi)Customizing synthetic organs: the 3D printing may represent an opportunity to save life reducing the waiting list of patients that need transplantation [72]. Bioprinted organs may also be used in the future by pharmaceutical industries to replace animal models for analyzing the toxicity of new drugs [73].

Therefore, these examples clearly demonstrated that 3D printing is one of the most disruptive technologies that have the potential to change significantly the clinical field, improving medicine and healthcare, making care affordable, accessible, and personalized. As printers evolve, printing biomaterials get safety regulated and the general public acquires a common sense about how 3D printing works.

4.1. Lack of Regulation

The biomedical field is one of the areas in which 3D printing has already shown its potentialities and that, in not too distant future, may be one of the key elements for the resolution of important problems related to human health that still exist.

Nowadays, despite the additive manufacturing offers a great potential for the manufacturing, the 3D-printing products do not have a proper legal status that defines them, both for implantable and nonimplantable devices. All the 3D-printed products are categorized as custom-made device under the Regulation (EU) 2017/745 of the European Parliament and of the Council of the 5 April 2017 [74]. They are defined as follow: “any device specifically made in accordance with a written prescription of any person authorized by national law by virtue of that person’s professional qualifications which gives, under that person’s responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs”. Differently for mass-produced devices “which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorized person shall not be considered to be custom-made devices” [75]. Indeed, manufacturers of custom-made devices shall only be guaranteed by an obligation of conformity assessment procedures upon which the device shall be compliant with safety and performance requirements [76]. Furthermore, the regulation states that “Devices, other than custom-made or investigational devices, considered to be in conformity with the requirements of this Regulation shall bear the CE marking of conformity” [77]. Thus, these medical devices do not require affixation of CE markings: a significant and constraining procedure demonstrating the safety and the performance of the device for the patient. Moreover, the custom-made devices do not require the UDI System (Unique Device Identification system) as reported in the Article 27, Comma 1 of the regulation.

A different approach has to be applied for custom-made implants, such as dental prostheses, that are defined as “any device, including those that are partially or wholly absorbed, which is intended:(i)to be totally introduced into the human body, or(ii)to replace an epithelial surface or the surface of the eye,by clinical intervention and which is intended to remain in place after the procedure.

Any device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30 days shall also be deemed to be an implantable.” [78]. The custom-made implantable devices require the CE marking in order to guarantee the safety and to be commercialized.

The EU has been working for many years on an update to the Medical Devices Directive. This proposed legislation has many noble attributes in addition to overcoming the gaps of the existing Medical Devices Directive, such as supporting technology and science innovation, while simultaneously strengthening patient safety. However, the current version of the draft Regulation lacks some depth that is mandatory to safeguard safe usage of 3D-printing technology and, thus, enable its increasing prevalence in medicine.

4.2. Examples of Application of 3D Printing in Paediatric Cases

Three-dimensional (3D) modelling and printing greatly supports advances in individualized medicine and surgery. Looking to the field of paediatrics, it is possible to identify four main applications categories: surgical planning, prostheses, tissue construct, and drug printing.

There are many successful cases that demonstrate the potential of the additive manufacturing in surgical planning in paediatric cases. In particular, most of the applications of 3D printing reported in the literature are related to the congenital heart disease [29]. This is due to the fact that children have a smaller chest cavity than adults, and the surgical treatment in paediatric cases may be much more difficult. The additive manufacturing helps the surgeons to have more information than the only ones that imaging technologies can afford. It helps the surgeon in the spatial orientation inside the cavities of a small infant heart and in simulating the surgical approach and steps of the operation with high fidelity [79]. This leads to shorter intraoperative time that per se has significant impact on complication rate, blood loss, postoperative length-of-stay, and reduced costs [80]. An example of the application of the 3D printing in the paediatric congenital heart disease treatment is a study reported in the literature based on the development of a 3D heart model of a 15-years-old boy to improve interventional simulation and planning in patient with aortic arch hypoplasia. The 3D-printed model allowed simulation of the stenting intervention. The assessment of optimal stent position, size, and length was found to be useful for the actual intervention in the patient. This represents one of the most technically challenging surgical procedures which opens the door for potential simulation applications of a 3D model in the field of catheterization and cardiovascular interventions [81].

Another study proposed in which the 3D printing had a relevant role consists in a clinical preoperative evaluation on five patients ranged from 7 months to 11 years of age affected by a double outlet right ventricle with two well-developed ventricles and with a remote ventricular septal defect. The three-dimensional printed model based on the data derived from computed tomography (CT) or magnetic resonance (MRI) contributed to a more complete appreciation of the intracardic anatomy, leading to a successful surgical repair for three of the five patients. [82] Lastly, CT and MRI data were used to construct 3D digital and anatomical models to plan a heart transplantation surgical procedure of two patients of 2 and 14 years old affected relatively by hypoplastic left heart syndrome and pulmonary atresia with a hypoplastic right ventricle. These physical models allowed the surgeon and the paediatric cardiologist to develop the optimal surgical treatment during the heart transplantation anticipating problems that may arise during the procedure. The specific dimensions and distances can be measured, and heart transplantation can be planned [83].

The importance of three-dimensional printing has been demonstrating also in other application. The additive manufacturing in fact has been used to plan surgical treatment of paediatric orthopaedic disorders [84]. The 3D model of a 2-year-old male child was produced in order to plan the surgical treatment for his multisutural craniosynostosis with a history of worsening cranial deformity. Other than the turribrachycephalic skull, the child also had greatly raised intracranial pressure with papilledema and copper beaten appearance of the skull. Thorough preoperative planning enabled faster surgery and decreased anesthesia time in a compromised patient [85].

Another study, based on 13 cases of multiplane spinal or pelvic deformity, was developed in order to demonstrate that the three-dimensional printing may represent a useful tool in the surgical planning of complex paediatric spinal deformities treatment [86].

Changing the final goal of the additive manufacturing, other applications cases are reported in the literature to demonstrate the usefulness in the production of paediatric patient-specific prostheses. An example in the literature is given by the development of a low-cost three-dimensional printed prosthetic hand for children with upper-limb reductions using a fitting methodology that can be performed at a distance [87]. This specific case demonstrates that the advancements in computer-aided design (CAD) programs, additive manufacturing, and imaging editing software offer the possibility of designing, printing, and fitting prosthetic hands devices overcoming the costs limitation. As a consequence, the advantages of 3D-printed implants over conventional ones are in terms of customizability and cost as seems to be clear from the previous example. On the contrary, the major adversity is related to the rapid physical growth that makes the customize prostheses outsized frequently. This leads to the production of advanced technological implant that, due to their high complexity and weight, increases cost. The additive manufacturing can be used to fabricate rugged, light-weight, easily replaceable, and very low-cost prostheses for children [88]. The major prostheses lack is related to the ability to communicate with the brain in terms of sensibility. With the advent of bioprinting, cellular prostheses could be an interesting area of research, which can lead to integrated prostheses in the brain communication system, and exhibit more biomimicry with tissue and organ functionalities [89].

Related to bioprinting, there are few applications nowadays involved in the tissues production in regenerative medicine. Many different tissues have been successfully bioprinted as reported in many journal articles [90] including bone, cartilage, skin, and even heart valves. However, the bioprinted tissues and organs are at the laboratory level; a long way needs to be travelled to achieve successful clinical application [91].

Last but not the least, the additive manufacturing in terms of drug printing may also represent an innovative technique in the production of patient-specific medicine with regard to the composition and the dose needed by the patients. The drug-printing introduces the concept of tailor-made drugs in order to make drugs safer and more effective. Especially for children, furthermore, drug-printing represents the possibility of choosing colour, shape, and design of the medication, reducing the resistance in taking them. Imagine a paediatrician talking to a four-year-old child who is having trouble adjusting to taking daily doses of steroids after being diagnosed with Duchenne muscular dystrophy the previous month. 3D printing allows us to design in particular shape the drug, making medicine more appealing to the child [92]. It is amental to note that changing the shape of a capsule does not have to lead to different dose and drug properties, such as drug release or dissolution rate [93].

5. Conclusions

The 3D printing in medical field and design needs to think outside the norm for changing the health care. The three main pillars of this new technology are the ability to treat more people where it previously was not feasible, to obtain outcomes for patients and less time required under the direct case of medical specialists. In few words, 3D printing consists in “enabling doctors to treat more patients, without sacrificing results” [94].

Therefore, like any new technology, 3D printing has introduced many advantages and possibilities in the medical field. Each specific case in which 3D printing has found application shown in this analysis is a demonstration of this. However, it must be accompanied by an updated and current legislation in order to guarantee its correct use.

Conflicts of Interest

The authors declare that there are no conflicts of interest regarding the publication of this paper.


The publication of the article was funded through the collaboration between Aid4Med S.r.l. and the Universitè Libre de Bruxelles.


  1. H. Arun, Healthcare 3D Printing Market 2018 Prominent Players-Aprecia Pharmaceuticals, Aspect Biosystems, Bio 3D Technologies, Biobots, Cyfuse Biomedical, Digilab, 3 Dynamics Systems, Envision Tec, Luxexcel, Materialise NV, Nano 3D Biosciences, Oceanz, Organovo Ho,
  2. C. L. Ventola, “Medical applications for 3D printing: current and projected uses,” Pharmacy and Therapeutics, vol. 39, no. 10, pp. 704–711, 2014. View at Google Scholar
  3. D. B. Jones, R. Sung, C. Weinberg, T. Korelitz, and R. Andrews, “Three-dimensional modeling may improve surgical education and clinical practice,” Surgical Innovation, vol. 23, no. 2, pp. 189–195, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. I. M. Mazher, P. F. Angus, K. M. Santosh, and I. Gibson, “Customised design and development of patient specific 3D printed whole mandible implant,” in Proceedings of the 27th Annual International Solid Freeform Fabrication Symposium, Austin, TX, USA, August 2016.
  5. D. C. Ackland, D. Robinson, M. Redhead, P. Vee Sin Lee, A. Moskaljuk, and G. Dimitoulis, “A personalized 3D-printed prosthetic joint replacement for the human temporomandibular joint: From implant design to implantation,” Journal of the Mechanical Behavior of Biomedical Materials, vol. 69, pp. 404–411, 2017. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Phan, A. Sgro, M. M. Maharaj, P. D’Urso, and R. J. Mobbs, “Application of a 3D custom printed patient specific spinal implant for C1/2 arthrodesis,” Journal of Spine Surgery, vol. 2, no. 4, pp. 314–318, 2016. View at Publisher · View at Google Scholar
  7. L. E. Diment, M. S. Thompson, and J. H. M. Bergmann, “Clinical efficacy and effectiveness of 3D printing: a systematic review,” BMJ Open, vol. 7, no. 12, Article ID e016891, 2017. View at Publisher · View at Google Scholar · View at Scopus
  8. J. Garcia, Z. Yang, R. Mongrain, R. L. Leask, and K. Lachapelle, “3D printing materials and their use in medical education: a review of current technology and trends for the future,” BMJ Simulation and Technology Enhanced Learning, vol. 4, no. 1, pp. 27–40, 2017. View at Publisher · View at Google Scholar
  9. R. J. Mondschein, A. Kanitkar, C. B. Williams, S. S. Verbridge, and T. E. Long, “Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds,” Biomaterials, vol. 140, pp. 170–188, 2017. View at Publisher · View at Google Scholar · View at Scopus
  10. W. Zhu, X. Ma, M. Gou, D. Mei, K. Zhang, and S. Chen, “3D printing of functional biomaterials for tissue engineering,” Current opinion in biotechnology, vol. 40, pp. 103–112, 2016. View at Publisher · View at Google Scholar · View at Scopus
  11. ASTM, Standard Technology for Additive Manufacturing-General Principles/Terminology, ASTM ISO/ASTM 52900:2015 (E), West Conshohocken, PA, USA, 2015.
  12. H. J. Chen and M. Gariel, Aroadmap from Idea to Implementation–3D Printing for Pre-Surgical Applications, CreateSpace Independent Publishing Platform, Scotts Valley, CA, USA, 1st edition, 2012.
  13. A. Cohen, A. Laviv, P. Berman, R. Nashef, and J. Abu-Tair, “Mandibular reconstruction using stereolithographic 3-dimensional printing modeling technology,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, vol. 108, no. 5, pp. 661–666, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. D. Whitley, R. S. Eidson, I. Rudek, and S. Bencharit, “In-office fabrication of dental implant surgical guides using desktop stereolithographic printing and implant treatment planning software: a clinical report,” Journal of Prosthetic Dentistry, vol. 118, no. 3, pp. 256–263, 2017. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Dodziuk, “Application of 3D printing in healthcare,” Kardiochirurgia i Torakochirurgia Polska, vol. 13, no. 3, pp. 283–293, 2017. View at Google Scholar
  16. D. Ibrahim, T. L. Broilo, C. Heitz et al., “Dimensional error of selective laser sintering, three-dimensional printing and PolyJet models in the reproduction of mandibular anatomy,” Journal of Cranio-Maxillofacial Surgery, vol. 37, no. 3, pp. 167–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. J. S. Matsumoto, J. M. Morris, T. A. Foley et al., “Three-dimensional physical modelling: applications and experience at mayo clinic,” RadioGraphics, vol. 35, no. 7, pp. 1989–2006, 2015. View at Publisher · View at Google Scholar · View at Scopus
  19. Medtronic case study, Custom surgical instruments becoming working prototypes using FDM 3D printing technology.
  20. K. S. Tanaka and N. Lightdale-Miric, “Advances in 3d-printed pediatric prostheses for upper extremity differences,” Journal of Bone and Joint Surgery, vol. 98, no. 15, pp. 1320–1326, 2016. View at Publisher · View at Google Scholar · View at Scopus
  21. S. L. Sing, J. An, W. Y. Teong, and F. E. Wiria, “Laser and electron beam powder-bed additive manufacturing of metallic implants: a review on processes, materials and designs,” Journal of Orthopaedic Research, vol. 34, no. 3, pp. 369–385.
  22. F. Auricchio and S. Marconi, “3D printing: clinical applications in orthopaedics and traumatology,” EFORT Open Reviews, vol. 1, no. 5, pp. 121–127, 2016. View at Publisher · View at Google Scholar
  23. C. G. Helguero, V. M. Mustahsan, S. Parmar et al., “Biomechanical properties of 3D-printed bone scaffolds are improved by treatment by CRFP,” Journal of Orthopaedic Surgery and Reasearch, vol. 12, no. 1, p. 195, 2017. View at Publisher · View at Google Scholar · View at Scopus
  24. M. Asadi-Edyvand, M. Solati-Hasjin, A. Farzad, and N. A. A. Osman, “Effect of technical parameters on porous structure and strength of 3D printed calcium sulfate prototypes,” Robotics and Computer-Integrated Manufacturing, vol. 37, pp. 57–67, 2015. View at Google Scholar
  25. M. S. Mannoor, Z. Jiang, T. James et al., “3D printed bionic ears,” Nano Letters, vol. 13, no. 6, pp. 2634–2639, 2013. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Vukievic, B. Mosadegh, J. K. Little, and S. H. Little, “Cardiac 3D printing and its future directions,” JACC: Cardiovascular Imaging, vol. 10, no. 2, pp. 171–184, 2017. View at Publisher · View at Google Scholar · View at Scopus
  27. D. S. C. Soon, M. P. Chae, C. H. C. Pilgrim, W. M. Rozen, R. T. Spychal, and D. J. Hunter-Smith, “3D haptic modelling for preoperative planning of hepatic resection: a systematic review,” Annals of Medicine and Surgery, vol. 10, pp. 1–7, 2016. View at Publisher · View at Google Scholar · View at Scopus
  28. I. Abudayyeh, B. Gordon, M. M. Ansari, K. Jutzy, L. Stoletniy, and A. Hilliard, “A practical guide to cardiovascular 3D printing in clinical practice: overview and examples,” Journal of Interventional Cardiology, vol. 31, no. 3, pp. 375–383, 2017. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Cantinotti, I. Valverde, S. Kutty, and J. Eckert, “Three-dimensional printed models in congenital heart disease,” International Journal of Cardiovascuolar Imaging, vol. 33, no. 1, pp. 137–144, 2016. View at Publisher · View at Google Scholar · View at Scopus
  30. Stratasys, Case study, Dante Pazzanese Cardiology Institute uses 3D printed arteries to diagnose and treat diseases.
  31. Stratasys, Case study, Shaping Young Hearts. Stratasys Helps a Surgeon Save More Kids.
  32. K. Qiu, G. Haghiashtiani, and M. C. McAlpine, “3D printed organ models for surgical applications,” Annual Review of Analytical Chemistry, vol. 11, no. 1, pp. 287–306, 2018. View at Publisher · View at Google Scholar · View at Scopus
  33. E. M. Zanetti, A. Aldieri, M. Terzini, M. Calì, G. Franceschini, and C. Bignardi, “Additively manufactured custom load-bearing implantable devices: grounds for caution,” Australasian Medical Journal, vol. 10, no. 8, pp. 694–700, 2017. View at Publisher · View at Google Scholar · View at Scopus
  34. S. N. Kurenov, C. Ionita, D. Sammons, and T. L. Demmy, “Three-dimensional printing to facilitate anatomic study, device development, simulation, and planning in thoracic surgery,” Journal of Thoracic and Cardiovascular Surgery, vol. 149, no. 4, pp. 973–979, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. H. Jeon, K. Kang, S. A. Park et al., “Generation of multilayered 3D structures of HepG2 cells using a bio-printing technique,” Gut and Liver, vol. 11, no. 1, pp. 121–128, 2017. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Randazzo, J. M. Pisapia, N. Singh, and J. P. Thawani, “3D printing in neurosurgery: a systematic review,” Surgical Neurology International, vol. 7, no. 34, pp. 801–809, 2016. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Lino, K. Igawa, Y. Kanno et al., “Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology,” Journal of artificial organ, vol. 12, no. 3, pp. 200–205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. W. Huang and X. Zhang, “3D printing: print the future of ophthalmology,” Investigative Opthalmology & Visual Science, vol. 55, no. 8, pp. 5380-5381, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. T. D. Crafts, S. E. Ellsperman, T. J. Wannemuehler, T. D. Bellicchi, T. Z. Shipchandler, and A. V. Mantravadi, “Three-dimensional printing and its applications in otorhinolaryngology-head and neck surgery,” Otolaryngology-Head and Neck Surgery, vol. 156, no. 6, pp. 999–1010, 2017. View at Publisher · View at Google Scholar · View at Scopus
  40. M. P. Chae, W. M. Rozen, P. G. McMenamin et al., “Emerging applications of bedside 3D printing in plastic surgery,” Frontiers in Surgery, vol. 16, no. 2, p. 25, 2015. View at Google Scholar
  41. C. Williams, A. James, M. P. Chae, and D. J. Hunter-Smith, “3D printing in clinical podiatry: a pilot study and review,” Journal of Foot and Ankle Research, vol. 8, no. 2, p. 41, 2015. View at Publisher · View at Google Scholar
  42. N. Guilbert, L. Mhanna, A. Didier et al., “Integration of 3D printing and additive manufacturing in the interventional pulmonologist’s toolbox,” Respiratory Medicine, vol. 134, pp. 139–142, 2018. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Su, K. Moran, and J. L. Robar, “Design and production of 3D printed bolus for electron radiation therapy,” Journal of Applied Clinical Medical Physics, vol. 15, no. 4, pp. 194–211, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. N. N. Zein, I. A. Hanouneh, P. D. Bishop et al., “Three-dimensional print of a liver for preoperative planning in living donor liver transplantation,” Liver transplantation, vol. 19, no. 12, pp. 1304–1310, 2013. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Soliman, A. H. Feibus, and N. Baum, “3D printing and its urologic applications,” Urology, vol. 17, no. 1, pp. 20–24, 2017. View at Google Scholar
  46. P. Hangge, Y. Pershad, A. A. Witting, H. Albadawi, and R. Oklu, “Three-dimensional (3D) printing and its applications for aortic diseases,” Cardiovascular Diagnosis & Therapy, vol. 8, no. 1, pp. 19–25, 2018. View at Publisher · View at Google Scholar · View at Scopus
  47. D. H. Ballard, A. P. Trace, S. Ali et al., “Clinical applications of 3D printing,” Academic Radiology, vol. 25, no. 1, pp. 52–65, 2018. View at Publisher · View at Google Scholar · View at Scopus
  48. E. Perica and Z. Sun, “Patient-specific three-dimensional printing for pre-surgical planning in hepatocellular carcinoma treatment,” Quantitative Imaging in Medicine and Surgery, vol. 7, no. 6, pp. 668–677, 2017. View at Publisher · View at Google Scholar · View at Scopus
  49. E. O’Brien, D. B. Wayne, K. A. Barsness, W. C. McGaghie, and J. H. Barsuk, “Use of 3D printing for medical education models in transplantation medicine: a critical review,” Current Transplantation Reports, vol. 3, no. 1, pp. 109–119, 2016. View at Publisher · View at Google Scholar
  50. K. C. Wong, “3D-printed patient-specific applications in orthopedics,” Orthopedic Research and Reviews, vol. 8, pp. 57–66, 2016. View at Publisher · View at Google Scholar · View at Scopus
  51. J. P. Costello, R. J. Olivieri, L. Su et al., “Incorporating three-dimensional printing into a simulation-based congenital heart-disease and critical care training curriculum for resident physiscians,” Congenital Heart Disease, vol. 10, no. 2, pp. 185–190, 2015. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Frame and J. S. Huntley, “Rapid prototyping in orthopaedic surgery: a user’s guide,” Scientific World Journal, vol. 2012, Article ID 838575, 7 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Mahaisavariya, K. Sitthiseripratip, P. Oris, and T. Tongdee, “Rapid prototyping model for surgical planning of corrective osteotomy for cubitus varus: report of two cases,” Injury Extra, vol. 37, no. 5, pp. 176–180, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. U. Sheth, J. Theodoropoulos, and J. Abouali, “Use of 3-dimensional printing for preoperative planning in the treatment of recurrent anterior shoulder instability,” Arthroscopy Techniques, vol. 4, no. 4, pp. 311–316, 2015. View at Publisher · View at Google Scholar · View at Scopus
  55. Stratasys, Case study, 3D Printing for Vascular Health. Shaping Breakthroughs in Brain Aneurysm Treatments.
  56. Y.-T. Wang, X.-J. Yang, B. Yan, T.-H. Zeng, Y.-Y. Qiu, and S.-J. Chen, “Clinical application of three-dimensional printing in the personalized treatment of complex spinal disorders,” Chinese Journal of Traumatology, vol. 19, no. 1, pp. 31–34, 2016. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Hosny, J. D. Dilley, M. Mathur et al., “Pre-procedural fit-testing of TAVR valves using parametric modeling and 3D printing,” Journal of Cardiovascular Computed Tomography, vol. 18, 2018. View at Google Scholar
  58. R. Vaishya, V. Vijay, A. Vaish, and A. K. Agarwal, “Computed tomography based 3D printed patient specific blocks for total knee replacement,” Journal of Clinical Orthopaedics and Trauma, vol. 9, no. 3, pp. 254–259, 2018. View at Publisher · View at Google Scholar · View at Scopus
  59. X. Chen, J. K. Possel, C. Wacongne, A. F. Van Ham, P. C. Klink, and P. R. Roelfsema, “3D printing and modelling of customized implants and surgical guides for non-human primates,” Journal of Neuroscience Methods, vol. 286, no. 286, pp. 38–55, 2017. View at Publisher · View at Google Scholar · View at Scopus
  60. A. De La Pena, J. De La Pena-Brambila, J. Perez-De La Torre, M. Ochoa, and M. J. Gallardo, “Low-cost customized craniolplasty using a 3D digital printing model: a case report,” 3D Printing in Medicine, vol. 4, no. 1, 2018. View at Publisher · View at Google Scholar
  61. Stratasys, Case study, Printing Pathways to Medical Innovation. 3D Printing’s Versatility Paves the Way for Medical Advancements by Cardiovascular Systems, Inc..
  62. K. R. Rosen, “The history of medical simulation,” Journal of Critical Care, vol. 23, no. 2, pp. 157–166, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. V. Walker, “Implementing a 3D printing service in a biomedical library,” Journal of the Medical Library Association, vol. 105, no. 1, pp. 55–60, 2017. View at Publisher · View at Google Scholar · View at Scopus
  64. K. Wang, C. Wu, Z. Qian, C. Zhang, B. Wang, and M. A. Vannan, “Dual-material 3D printed metamaterials with tunable mechanical properties for patient-specific tissue-mimicking phantoms,” Additive Manufacturing, vol. 12, pp. 31–37, 2016. View at Publisher · View at Google Scholar · View at Scopus
  65. K. H. A. Lim, Z. Y. Loo, S. J. Goldie, J. W. Adams, and P. G. McMenamin, “Use of 3D printed models in medical education: a randomized control trial comparing 3D prints versus cadaveric materials for learning external cardiac anatomy,” Anatomical Sciences Education, vol. 9, no. 3, pp. 213–221, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. J.-C. Bernhard, S. Isotani, T. Matsugasumi et al., “Personalized 3D printed model of kidney and tumor anatomy: a useful tool for patient education,” World Journal of Urology, vol. 34, no. 3, pp. 337–345, 2016. View at Publisher · View at Google Scholar · View at Scopus
  67. C. Andolfi, A. Plana, P. Kania, P. P. Banerjee, and S. Small, “Usefulness of three-dimensional modeling in surgical planning, resident training, and patient education,” Journal of Laparoendoscopic & Advanced Surgical Techniques, vol. 27, no. 5, pp. 512–515, 2017. View at Publisher · View at Google Scholar · View at Scopus
  68. W. Baier, J. M. Warnett, M. Payne, and M. A. Williams, “Introducing 3D printed models as demonstrative evidence at criminal trials,” Journal of Forensic Sciences, vol. 63, no. 4, pp. 1298–1302, 2017. View at Publisher · View at Google Scholar · View at Scopus
  69. P. He, J. Zhao, J. Zhang et al., “Bioprinting of skin constructs for wound healing,” Burns & Trauma, vol. 6, no. 1, 2018. View at Publisher · View at Google Scholar
  70. G. Zhou, H. Jiang, Z. Yin et al., “In vitro regeneration of patient-specific ear-shaped cartilage and its first clinical application for auricular reconstruction,” EBioMedicine, vol. 28, pp. 287–302, 2018. View at Publisher · View at Google Scholar · View at Scopus
  71. A. Konta, M. García-Piña, and D. Serrano, “Personalised 3D printed medicines: which techniques and polymers are more successful?” Bioengineering, vol. 4, no. 4, p. 79, 2017. View at Publisher · View at Google Scholar
  72. S. Ji and M. Guvendiren, “Recent advances in bioink design for 3D bioprinting of tissues and organs,” Frontiers in Bioengineering and Biotechnolgy, vol. 5, no. 5, p. 23, 2017. View at Publisher · View at Google Scholar
  73. N. Charbe, P. A. McCarron, and M. M. Tambuwala, “Three-dimensional bio-printing: a new frontier in oncology research,” World Journal of Clinical Oncology, vol. 8, no. 1, pp. 21–36, 2017. View at Publisher · View at Google Scholar · View at Scopus
  74. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and regulation (EC) No 1223/2009 and repealing Council Directive 90/985/EEC and 93/42/EEC.
  75. Article 2, Comma 3 of the Regulation (EU) 2017/745.
  76. Article 20, Comma 1 of the Regulation (EU) 2017/745.
  77. Article 10 of the Regulation (EU) 2017/745.
  78. Article 2, Comma 5 of the Regulation (EU) 2017/745.
  79. L. Kiraly and S. Khalifa, “Three-dimensional modelling and three-dimensional printing in pediatric and congenital cardiac surgery,” Translational Pediatrics, vol. 7, no. 2, pp. 129–138, 2018. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Maruthappu, A. Duclos, S. R. Lipsitz, and D. Orgill, “Surgical learning curves and operative efficiency: a cross-speciality observational study,” BMJ Open, vol. 5, no. 3, Article ID e006679, 2015. View at Publisher · View at Google Scholar · View at Scopus
  81. I. Valverde, G. Gomez, J. F. Coserria et al., “3D printed models for planning endovascular stenting in transverse aortic arch hypoplasia,” Catheterization and Cardiovascular Interventions, vol. 85, no. 6, pp. 1006–1012, 2015. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Garekar, A. Bharati, M. Chokhandre et al., “Clinical application and multidisciplinary assessment of three dimensional printing in double outlet right ventricle with remote ventricular septal defect,” World Journal for Pediatric and Congenital Heart Surgery, vol. 7, no. 3, pp. 344–350, 2016. View at Publisher · View at Google Scholar
  83. R. Sodian, S. Weber, M. Markert et al., “Pediatric cardiac transplantation: three-dimensional printing of anatomic models for surgical planning of heart transplantation in patients with univentricular heart,” Journal of Thoracic and Cardiovascular Surgery, vol. 136, no. 4, pp. 1098-1099, 2008. View at Publisher · View at Google Scholar · View at Scopus
  84. Z. A. Starosolski, J. H. Kan, S. D. Rosenfeld, R. Krishnamurthy, and A. Annapragada, “Application of 3-D printing (rapid prototyping) for creating physical models of pediatric orthopedic disorders,” Pediatric Radiology, vol. 44, no. 2, pp. 216–221, 2014. View at Publisher · View at Google Scholar · View at Scopus
  85. D. A. Mendonca, V. Deraje, R. S. Gujjalanavar, and S. Gopal, “Case series of three-dimensional printing technology applied in complex craniofacial deformity surgery,” Journal of Lip Palate and Craniofacial Anamalies, vol. 3, no. 2, pp. 88–94, 2016. View at Publisher · View at Google Scholar
  86. J. Guarino, S. Tennyson, G. McCain, L. Bond, K. Shea, and H. King, “Rapid prototyping technology for surgeries of the pediatric spine and pelvis,” Journal of Pediatric Orthopaedics, vol. 27, no. 8, pp. 955–960, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. J. Zuniga, D. Katsavelis, J. Peck et al., “Cyborg beast: a low-cost 3D-printed prosthetic hand for children with upper-limb differences,” BMC Research Notes, vol. 8, no. 1, pp. 8–10, 2015. View at Publisher · View at Google Scholar · View at Scopus
  88. M. B. Burn and G. R. Gogola, “Three-dimensional printing of orosthetic hands for children,” Journal of Hand Surgery, vol. 41, no. 5, pp. 103–109, 2016. View at Publisher · View at Google Scholar · View at Scopus
  89. Stratasys, Case Study, Skull Reconstruction. CTI Renato Archer 3D Prints Prototypes of an Accident Victim’s Skull.
  90. J. An, J. E. M. Teoh, R. Suntornnond, and C. K. Chua, “Design and 3D printing of scaffolds and tissues,” Engineering, vol. 1, no. 2, pp. 261–268, 2015. View at Publisher · View at Google Scholar · View at Scopus
  91. E. S. Bishop, S. Mostafa, M. Pakvasa et al., “3-D bioprinting technologies in tissue engineering and regenerative medicine: current and future trends,” Genes & Diseases, vol. 4, no. 4, pp. 185–195, 2017. View at Publisher · View at Google Scholar · View at Scopus
  92. K. Sanderson, “3D printing: the future of manufacturing medicine,” Pharmaceutical Journal, vol. 294, no. 7865, pp. 590–592, 2015. View at Google Scholar
  93. V. Sanjairaj, W. F. Lu, and J. Y. H. Fuh, “3D printing and 3D bioprinting in paediatrics,” Bioengineering, vol. 4, no. 4, p. 63, 2017. View at Publisher · View at Google Scholar
  94. S. Dunham, Surgeon’s Helper: 3D Printing is Revolutionizing Health Care (Op-Ed), SmarTech Markets, Charlottesville, VA, USA, 2015,