Tibial cortex transverse transport-derived small extracellular vesicles promote diabetic wound healing by enhancing angiogenesis and suppressing inflammation
摘要
Diabetic foot ulcer (DFU) is a severe complication of diabetes with limited therapeutic options. Tibial cortex transverse transport (TTT) shows clinical efficacy in DFU treatment, but its regenerative mechanisms remain unclear. Small extracellular vesicles (sEVs) have been implicated in bone-related tissue regeneration; however, their role in TTT-mediated wound healing has not been defined. A TTT rat model was established to investigate the contribution of sEVs to diabetic wound repair. Angiogenesis and inflammation were assessed using histology, immunofluorescence, qRT-PCR, and Western blotting. Plasma-derived sEVs from TTT-treated rats (TTT-sEVs) were isolated and evaluated for their effects on HUVECs and RAW264.7 macrophages in vitro. The therapeutic efficacy of TTT-sEVs was further examined in diabetic dorsal wounds using an sEV-loaded PF127 hydrogel. TTT significantly accelerated wound healing, enhanced angiogenesis, and reduced inflammation, whereas inhibition of sEV release attenuated these effects. TTT-sEVs promoted endothelial proliferation, migration, and tube formation, upregulated pro-angiogenic factors, and suppressed inflammatory mediators in macrophages. In vivo delivery of TTT-sEVs markedly improved diabetic wound healing and angiogenic responses. These findings demonstrate that sEVs are critical mediators of TTT-induced DFU repair by promoting angiogenesis and suppressing inflammation.