Platelet-rich plasma-derived exosomes accelerate the healing of diabetic foot ulcers by promoting macrophage polarization to the M2 phenotype

Diabetic foot ulcers (DFUs) impose a significant clinical and socioeconomic burden on patients and healthcare systems. Although platelet-rich plasma (PRP) and platelet-rich plasma-derived exosomes (PRP-Exos) have emerged as promising therapeutic agents in tissue regeneration, the mechanisms underlying the immunomodulatory effects of PRP and PRP-Exos—particularly their role in macrophage polarization—remain poorly understood. In this study, we isolated and characterized PRP-Exos and systematically evaluated their therapeutic potential in diabetic wound healing via comprehensive in vivo and in vitro experiments. Our results revealed that both PRP-gel and PRP-Exos significantly enhanced diabetic wound healing by promoting macrophage polarization toward the anti-inflammatory M2 phenotype. These findings suggest that PRP-Exos represent a novel and effective therapeutic strategy for DFUs, providing a robust rationale for future clinical translation.