Extracellular vesicle-loaded bacterial cellulose hydrogel for angiogenesis, inflammation control, and diabetic wound healing

Addressing chronic diabetic wounds remains a major clinical challenge because of persistent inflammation, impaired angiogenesis, bacterial infection, and delayed tissue regeneration. In this study, we developed a positively charged bacterial cellulose hydrogel loaded with M2 macrophage-derived small extracellular vesicles (PBC/sEVs) as a multifunctional wound dressing for diabetic wound repair. The cationic PBC matrix enabled efficient electrostatic binding of negatively charged sEVs while also providing intrinsic antibacterial activity. In vitro , the PBC/sEVs hydrogel significantly promoted the proliferation of fibroblasts (HFF-1) and endothelial cells (HUVECs), improved cellular activity, and enhanced tissue regenerative potential. Notably, the hydrogel exhibited strong antibacterial performance, achieving 84.2% bacterial eradication against Escherichia coli and 89.9% against Staphylococcus aureus. In vivo , the PBC/sEVs dressing markedly accelerated diabetic wound healing, with wound contraction exceeding 90% by day 14, accompanied by enhanced neovascularization, reduced inflammatory responses, and improved collagen deposition and re-epithelialization. These findings demonstrate that the PBC/sEVs hydrogel is a promising multifunctional dressing for chronic diabetic wound treatment and provides a practical strategy for the design of bioactive wound dressings with antibacterial, anti-inflammatory, and pro-angiogenic properties.