ADSC-derived exosomes deliver cerium oxide nanoparticles to promote diabetic wound healing via anti-inflammatory and pro-angiogenic effects

Diabetic wounds pose a significant clinical challenge due to excessive oxidative stress, chronic inflammation, and impaired angiogenesis. To address these issues, this study developed a novel nanocomposite, CeO₂@Exo, by loading cerium oxide nanoparticles (CeO₂ NPs) into adipose-derived stem cell-derived exosomes. In both in vitro and in vivo diabetic models, CeO₂@Exo effectively scavenged reactive oxygen species, promoted VEGF-mediated angiogenesis, and accelerated wound closure. Importantly, it modulated the inflammatory microenvironment by shifting macrophage polarization from the pro-inflammatory M1 to the pro-regenerative M2 phenotype, thereby enhancing the release of anti-inflammatory cytokines. These multifunctional effects demonstrate that CeO₂@Exo represents a promising, comprehensive therapeutic strategy for diabetic wound healing, overcoming the limitations of conventional single-target treatments.