Role of extracellular vesicles in wound healing

The therapeutic effects of exosomes are comparable to those of cell therapy. Additionally, their higher biocompatibility, lesser toxicity, and lower immunogenicity make them optimal candidates for research into regenerative medicine, particularly the field of wound healing. This review analyzes the data on the biological effects of exosomes during the different phases of wound healing in laboratory animals. The scientific data analysis results demonstrate the involvement of native exosomes in all phases of wound healing. Their primary source in hemostasis is platelets; in the inflammatory phase is neutrophils and monocytes; and in the proliferative phase is keratinocytes, fibroblasts, and endothelial cells. The greatest experimental therapeutic potential for uncomplicated skin wounds is shown by the exosomes derived from mesenchymal stem cells of various origins, including fibroblasts, endothelial cells, and epidermal stem cells. Their effects differ across the various wound healing phases. Exosomes are a heterogeneous group of nanoscale-sized structures with low immunogenic potential, capable of exerting selective influence on the mechanisms and phases of skin wound healing, during both the normal and disrupted courses of such phases. In translational medicine, the biological effects of exosomes can be optimized by selecting the cell source and adjusting the culture conditions per the therapeutic objectives. This report discusses three approaches to enhancing the effectiveness of exosome-based therapy: selecting their optimal source; modifying them either directly or indirectly via the source cells; and choosing the formulation for their optimal delivery. Hydrogels are considered the most promising wound dressing for encapsulating the extracellular vesicles, as they improve exosome stability, prolong their release into the wound, and provide a synergistic effect. Consequently, hydrogels are viewed as the preferred option for exosome encapsulation during wound treatment, since their wound-healing influence demonstrates synergism with the biological effects of exosomes.