Stem cell-derived biomimetic apoptotic vesicles enhance macrophage efferocytosis via C1qbp to accelerate diabetic wound healing

Chronic diabetic wounds represent a significant therapeutic challenge, characterized by persistent inflammation, impaired angiogenesis, and defective efferocytosis. In this study, we demonstrate that stem cell-derived biomimetic apoptotic vesicles (AVs) are enriched with complement C1q-binding protein (C1qbp), and confirm that C1qbp is a key regulator for macrophage phagocytosis. These AVs potently enhanced macrophage efferocytic activity, promoted polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, and reduced secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Moreover, AVs stimulated angiogenesis and cell migration, thereby initiating a coordinated immune-mediated tissue regenerative program. Delivery of AVs via a GelMA hydrogel (AVs@GelMA) markedly accelerated wound healing in diabetic mice by inhibiting nuclear factor-κB (NF-κB)-driven inflammatory signaling and promoting vascularization and tissue remodeling. Collectively, our findings elucidate a three-phase mechanism of "efferocytosis-immunity-regeneration" and highlight C1qbp-enriched AVs as a promising precision therapeutic strategy for chronic diabetic wounds.