Lactobacillus extracellular vesicle-driven oxygen-releasing photothermal hydrogel reprograms macrophages and promotes angiogenesis to accelerate diabetic wound healing

作者：Pingyun Yuan, Meng Deng, Xueru Li, Xiaotong Lu, Hui Yang, Ronghua Jin, Lan Wang, Mi Chen, Tian Bai, Tao Liu, Wenhao Zhou, Xiangdong Wang · 发表于：Bioactive Materials · 年份：2025 · DOI：10.1016/j.bioactmat.2025.08.010 · 被引用次数：16 · 研究领域：Extracellular vesicles in disease、Nanoplatforms for cancer theranostics、Electrospun Nanofibers in Biomedical Applications

Chronic wound healing remains clinically challenging due to insufficient angiogenesis coupled with persistent inflammatory microenvironments. Macrophage M2 polarization plays a pivotal role in resolving inflammation and promoting angiogenesis. Capitalizing on scalability and translational advantages, extracellular vesicles derived from Lactobacillus bulgaricus ( Lac -EVs) were employed to activate this mechanism. The anti-inflammatory and pro-angiogenic efficacy of Lac -EVs was initially confirmed through in vitro experiments. To support their delivery and function within the hostile diabetic wound microenvironment, a chitosan (CS)-based hydrogel incorporating haemoglobin (Hb)-polydopamine (PDA) complexes was engineered via Schiff base crosslinking with aldehyde-functionalised polyethylene glycol (CHO-PEG-CHO). This platform enabled stable delivery of Lac -EVs, supplemental oxygen release, and NIR-triggered photothermal functionality. In vitro studies demonstrated that the Lac -EVs-laden hydrogel (PCPH@ Lac -EVs) effectively induced M2 macrophage polarization, enhanced endothelial cell migration, and promoted angiogenesis. In murine full-thickness diabetic wounds, PCPH@ Lac -EVs combined with NIR irradiation achieved 99.3 % wound closure within 13 days, significantly outperforming untreated controls (72.3 %). Mechanistic analysis indicated that the accelerated healing resulted from synergistic enhancement of Lac -EV-mediated inflammation modulation and functional angiogenesis...