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Hypoxic wounds are tough to heal and are associated with chronicity, causing major healthcare burden. Available treatment options offer only limited success for accelerated and scarless healing. Traditional skin substitutes are widely used to improve wound healing, however, they lack proper vascularization. Mesenchymal stem cells (MSCs) offer improved wound healing; however, their poor retention, survival and adherence at the wound site negatively affect their therapeutic potential. The aim of this study is to enhance skin regeneration in a rat model of full-thickness dermal wound by transplanting genetically modified MSCs seeded on a three-dimensional collagen scaffold. Rat bone marrow MSCs were efficiently incorporated in the acellular collagen scaffold. Skin tissues with transplanted subcutaneous scaffolds were histologically analysed, while angiogenesis was assessed both at gene and protein levels. Our findings demonstrated that three-dimensional collagen scaffolds play a potential role in the survival and adherence of stem cells at the wound site, while modification of MSCs with jagged one gene provides a conducive environment for wound regeneration with improved proliferation, reduced inflammation and enhanced vasculogenesis. The results of this study represent an advanced targeted approach having the potential to be translated in clinical settings for targeted personalized therapy.

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Background: Time-dependent initiation of wound healing phases and their associated healing mediators are crucial for injured skin regeneration. Mesenchymal stem cells (MSCs) secrete various paracrine factors which aid in wound healing via acceleration of cell migration, angiogenesis, tissue granulation, and modulation of inflammation at the wound site. Objective: This study was aimed to investigate thetherapeutic effect of human umbilical cord MSCs (hUCMSCs) in the regeneration of cold-induced burn wound model. Methods: hUCMSCs were characterized by immunocytochemistry and flow cytometry. Scratch assay was performed using rat skin fibroblasts treated with conditioned medium of hUCMSCs. An in vivo cold burn wound model was developed and hUCMSCs were locally transplanted. Macroscopic analysis of wound closure was done at days 1, 3, 7 and 14 corresponding to wound healing phases. Gene expression, histology and immunohistochemical analysis were performed to confirm complete wound repair. Results: We observed a significant reduction in the scratch area in the treated group as compared to the control. Wound area was remarkably reduced in the burn wound model transplanted with hUCMSCs well before the end of the experimental period (day 14). Histology showed intact collagen with regenerated epidermis, dermis and hair follicles, while immunohistochemistry showed enhanced angiogenesis in the last phase of healing in the treated group. Temporal gene expression showed significant reduction in inflammatory cytokines and upregulation of pro/angiogenic and remodeling cytokines at particular time points. Conclusion: It is concluded from this study that hUCMSCs accelerate wound closure with enhanced neovascularization and reduced inflammation in rat dermal wounds.