Exosome-capturing scaffold promotes endogenous bone regeneration through neutrophil-derived exosomes by enhancing fast vascularization.

Exosomes (Exos), extracellular vesicles of endosomal origin, are a promising therapeutic platform for tissue regeneration. In the current study, an exosome-capturing scaffold (ECS) was designed to attract and anchor exosomes via electrostatic adherence followed by lipophilic interactions. Our findings demonstrate that local enrichment of exosomes in the ECS implanted into critical mandibular defects could significantly accelerate endogenous bone regeneration by enhancing vascularization at the defect site. Notably, neutrophil (PMN)-derived exosomes (PMN-Exos) were identified as the predominant exosome subtype among all captured exosomes. During endogenous bone regeneration, PMN-Exos promoted endogenous vascularization primarily by stimulating the proliferation of endothelial progenitor cells (EPCs), which play a pivotal role in the vasculogenesis of new blood vessels. Mechanistically, vascularization involved PMN-Exo-derived miR455-3p, which promotes EPC proliferation by targeting the Smad4 pathway. In conclusion, this study offers an ECS with broad application prospects for enhancing tissue regeneration by accelerating vascularization. The elucidation of underlying mechanisms paves the way for developing novel strategies to regenerate various tissues and organs.