Excessive and persistent inflammation after injury lead to chronic wounds, increased tissue damage or even aggressive carcinogenic transformation. Effective wound repair could be achieved by inhibiting overactive immune cells to the injured site. In this study, we obtained high concentration of PD-L1 in exosomes from either genetically engineered cells overexpressing PD-L1 or IFN-γ stimulated cells. We found that exosomal PD-L1 is specially bound to PD-1 on T cell surface, and suppressed T cell activation. Interestingly, exosomal PD-L1 promoted the migration of epidermal cells and dermal fibroblasts when pre-incubated with T cells. We further embedded exosomes into thermoresponsive PF-127 hydrogel, which was gelatinized at body temperature to release exosomes to the surroundings in a sustained manner. Of importance, in a mouse skin excisional wound model, exosomal PD-L1 significantly fastened wound contraction and reepithelialization when embedded in hydrogel during inflammation phase. Finally, exosomal PD-L1 inhibited cytokine production of CD8+ T cells and suppressed CD8+ T cell numbers in spleen and peripheral lymph nodes. Taken together, these data provide evidence on exosomal PD-L1 exerting immune inhibitory effects and promoting tissue repair.

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Mechanical stress following injury regulates the quality and speed of wound healing. Improper mechanotransduction can lead to impaired wound healing and scar formation. Vimentin intermediate filaments control fibroblasts’ response to mechanical stress and lack of vimentin makes cells significantly vulnerable to environmental stress. We previously reported the involvement of exosomal vimentin in mediating wound healing. Here we performed in vitro and in vivo experiments to explore the effect of wide-type and vimentin knockout exosomes in accelerating wound healing under osmotic stress condition. Our results showed that osmotic stress increases the size and enhances the release of exosomes. Furthermore, our findings revealed that exosomal vimentin enhances wound healing by protecting fibroblasts against osmotic stress and inhibiting stress-induced apoptosis. These data suggest that exosomes could be considered either as a stress modifier to restore the osmotic balance or as a conveyer of stress to induce osmotic stress-driven conditions.

Adipose stem cell-derived exosomes have great potential in accelerating cutaneous wound healing by optimizing fibroblast activities. Recent studies have demonstrated that exosomes play an active role in the transport of functional cytoskeletal proteins such as vimentin. Previously we showed that vimentin serves as a coordinator of the