In Situ Forming Nutritional and Temperature Sensitive Scaffold Improves the Esthetic Outcomes of Meshed Split-Thickness Skin Grafts in a Porcine Model.

Objective: Full-thickness burn wounds require immediate coverage, and the primary clinical approaches comprise of skin allografts and autografts. The use of allografts is often temporary due to the antigenicity of allografts. In contrast, the availability of skin autografts may be limited in large burn injuries. In such cases, skin autografts can be expanded through the use of a skin mesher, creating meshed split-thickness skin grafts (MSTSGs). MSTSGs have revolutionized the treatment of large full-thickness burn injuries since the 1960s. However, contractures and poor esthetic outcomes remain a problem. We previously formulated and prepared an in situ forming skin substitute, called MeshFill (MF), which can conform to complex shapes and contours of wounds. The objective of this study was to assess the esthetic and wound healing outcomes in full-thickness wounds treated with a combination of MF and MSTSG in a porcine model. Approach: Either MSTSGs or MSTSG+MF was applied to full-thickness excisional wounds in Yorkshire pigs. Wound healing outcomes were assessed using histology, immunohistochemistry, and wound surface area analysis from day 10 to 60. Clinical evaluation of wounds were utilized to assess esthetic outcomes. Results: The results demonstrated that the combination of MSTSGs and MF improved wound healing and esthetic outcomes. Innovation: Effects of MSTSGs and reconstitutable liquid MF in a full-thickness porcine model were investigated for the first time. Conclusion: MF provides promise as a combination therapeutic regimen to improve wound healing and esthetic outcomes.

Hypertrophic Scarring: Current Knowledge of Predisposing Factors, Cellular and Molecular Mechanisms.

Hypertrophic scarring (HSc) is an age-old problem that still affects millions of people physically, psychologically, and economically. Despite advances in surgical techniques and wound care, prevention and treatment of HSc remains a challenge. Elucidation of factors involved in the development of this common fibroproliferative disorder is crucial for further progress in preventive and/or therapeutic measures. Our knowledge about pathophysiology of HSc at the cellular and molecular level has grown considerably in recent decades. In this article, current knowledge of predisposing factors and the cellular and molecular mechanisms of HSc has been reviewed.

Split Thickness Grafts Grow From Bottom Up in Large Skin Injuries.

Autologous split thickness skin graft is necessary for the survival of patients with large burns and skin defects. It is not clear how a thin split thickness skin graft becomes remarkably thicker within a few weeks following transplantation. Here, we hypothesized that growth of split thickness graft should be from bottom up probably through conversion of immune cells into collagen producing skin cells. We tested this hypothesis in a preclinical porcine model by grafting split thickness meshed skin (0.508 mm thickness, meshed at 3:1 ratio) on full thickness wounds in pigs. New tissue formation was evaluated on days 10 and 20 postoperation through histological analysis and co-staining for immune cell markers (CD45) and type I collagen. The findings revealed that a split thickness graft grew from bottom up and reached to almost the same level as uninjured skin within 60 days postoperation. The result of immune-staining identified a large number of cells, which co-expressed immune cell marker (CD45) and collagen on day 10 postoperation. Interestingly, as the number of these cells reduced on day 20, most of these cells became positive for collagen production. In another set of experiments, we tested whether immune cells can convert to collagen producing cells in vitro. The results showed that mouse adherent immune cells started to express type 1 procollagen and α-smooth muscle actin when cultured in the presence of fibroblast conditioned media. In conclusion, the early thickening of split thickness graft is likely happening through a major contribution of infiltrated immune cells that convert into mainly collagen producing fibroblasts in large skin injuries.

Evaluation of Detergent-Free and Detergent-Based Methods for Decellularization of Murine Skin.

Acute and chronic wounds contribute to increased morbidity and mortality in affected people and impose significant financial burdens on healthcare systems. For these challenging wounds, acellular dermal matrices (ADMs) have been used as a biological wound coverage. Unlike engineered dermal matrices, ADMs are prepared through the removal of cells from skin, while preserving the extracellular matrix structure and function. In this study, our primary objective was to develop a detergent-free method for decellularization of the skin to mitigate chemical stress on matrix molecules. Then, we performed a set of in vitro and in vivo experiments to compare this method with nonionic and anionic detergent methods. All decellularization methods satisfactorily removed cells and supported fibroblast growth and migration in vitro. Sulfated glycosaminoglycan content was reduced significantly (p < 0.05) only in the ionic detergent treatment group. In contrast to the detergent-free method, all detergent-based methods significantly reduced scaffold mechanical strength and elastin content (p < 0.05). Three weeks after transplantation, the results showed reepithelialization, angiogenesis, and migration of host cell into scaffolds with no induction of immunogenic reaction in all ADM groups tested. In our study, the detergent-free method showed better preservation of matrix composition and biomechanical properties, but after transplantation, all methods of ADM preparation resulted in equally biofunctional matrices as wound coverage.