Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury.

Second-degree burns result in the loss of the epidermal barrier and could lead to delayed complications during the healing process. Currently, therapeutic options to treat severe burns are limited. Thus, this work aims to evaluate the effect of NaHS, a hydrogen sulfide (H2S) donor, in poloxamer hydrogel in topical application and the potentiating effect of injected encapsulated adipose-derived stem cells (ASCs) compared to monolayer ASCs using our previous second-degree burn model on human skin explants. Indeed, our model allows testing treatments in conditions similar to a clinical application. The observed benefits of NaHS may include an antioxidant role, which might be beneficial in the case of burns. Concerning ASCs, their interest in wound healing is more than well documented. In order to evaluate the efficiency of our treatments, we analyzed the kinetics of wound closure, keratinocyte proliferation, and dermal remodeling. The effect of NaHS led to a delay in re-epithelialization, with a decrease in the number of proliferating cells and a decrease in the synthesis of procollagen III. On the contrary, intradermal injection of ASCs, encapsulated or not, improves wound healing by accelerating re-epithelialization and collagen I synthesis; however, only encapsulated ASCs accelerate keratinocyte migration and increase the rate of procollagen III and collagen III. In conclusion, NaHS treatment did not improve burn healing. However, the injection of ASCs stimulated wound healing, which is encouraging for their therapeutical use in burn treatment.