Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Burn Wound Healing

Severe cutaneous burns induce profound immune, metabolic and wound healing disturbances, leading to major local and systemic consequences. Despite advances in surgical management, clinical outcomes remain frequently unsatisfactory, characterized by uncertain graft take, prolonged healing times and the frequent development of pathological scarring. In this context, mesenchymal stromal cells (MSCs) have attracted considerable interest, primarily due to their paracrine immunomodulatory and pro regenerative effects. However, their clinical application remains limited by safety concerns, biological variability and implementation constraints. To address these limitations, an acellular therapeutic strategy based on extracellular vesicles (EVs) derived from MSCs, considered key mediators of their paracrine activity, has been developed. Accordingly, a manufacturing process for EV enriched secretome products, used either alone or in combination with soluble factors, was established while integrating regulatory constraints associated with the production of biological medicinal products. The resulting products were characterized and subsequently evaluated in experimental burn models. Biological activity was investigated in vitro using relevant cutaneous and immune cell models of post burn wound healing, enabling the assessment of inflammation modulation, cellular proliferation and migration. These findings were complemented by in vivo studies in a murine model of cutaneous injury under inflammatory conditions, with evaluation of wound closure, the quality of repaired tissue and the local inflammatory response.