Review Article

Nanotechnology-Based Therapies for Skin Wound Regeneration

Table 1

Executive summary table.

Inflammation
(i) thrombin is one of the first products of the coagulation cascade occurring during haemostasis, and is responsible for platelet activation and aggregation, leading to the formation of the “platelet plug” and allowing cells and fluid to enter the wound bed. In human plasma, thrombin is rapidly degraded (15 sec). In order to provide long-term protection, it has been conjugated with iron-oxide nanoparticles for treatment of incisional wounds in rats [15]
(ii) bacterial infection and sepsis exacerbate the inflammatory state and cause tissue damage
 (a) nanoparticles bearing vancomycin or N-methyltiolated β lactams have been developed to act against wound contamination by MRSA [1619]
 (b) silver-based nanoparticles were developed to take advantage on the multilevel antibacterial action of silver and try to reduce the development of microbial resistance. Pure biostable nanoparticles were produced through photoassisted reduction and ion stabilization. Silver nanoparticles were also loaded into nanofibers [20]. A direct promotion of wound healing by silver nanoparticles through reduction of the cytokine-modulated inflammation and cell migration and proliferation was also demonstrated [21, 22]
 (c) donor NO silica nanoparticles showed speed healing by killing both Gram-positive and Gram-negative bacteria and overcoming the NO deficiency [23]. No-releasing nanoparticles may also potentially accelerate healing by a promotion of angiogenesis and tissue remodelling [24]

Proliferation
(i) the aim of growth factors is to promote cell migration into the wound site, stimulate the growth of epithelial cells and fibroblasts, start the formation of new blood vessels, and profoundly influence the remodelling of the scar. To enhance the in vivo efficacy of growth factors they have been incorporated into polymer nanocarriers to sustain release. PLA/PLGA/PEG/hyaluronan/gelatin nanoparticles embedded with different growth factors have been successfully applied on skin wounds [2531]
(ii) opioids have been recently indicated as factors promoting keratinocytes migration. Solid lipid nanoparticles were embedded with opioids, confirming the influence of these drugs on keratinocytes migration [32, 33]
(iii) nanofibrous scaffolds: electrospunnanofibers networks support cell adhesion, proliferation, and differentiation mimicking the fibrous architecture of the extracellular matrix. Both degradable (collagen and chitosan) and nondegradable (PLA, PVA, PLACL, and polyurethane) fibers are used for 2D and 3D constructs [3436]. Scaffolds were also engineered to contain growth factors-releasing nanoparticles enhancing wound repair [37]

Remodelling
(i) matrix metalloproteinase collagenolytic activity appears to be upregulated in chronic wounds. Protease inhibitors were loaded into human derived nanoparticles, showing a proresolving action and accelerated healing [38]
(ii) gene therapy: nonviral polymeric gene delivery systems offer increased protection from nuclease degradation, enhanced plasmid DNA uptake, and controlled dosing to sustain the duration of plasmid DNA administration. Gene delivery systems are formulated from PLGA polymers, polysaccharides, and chitosan [3941]
(iii) stem cells: cell-based therapies hold the potential to promote vascularization and tissue regeneration. The hVEGF gene was delivered through biodegradable polymeric nanoparticles: treated stem cells showed the engraftment of the tissue [42]