A tea exosome-integrated self‑oxygenating cascade chitosan/oxidized alginate hydrogel for remodeling the hyperglycemic and hypoxic microenvironment in diabetic wound healing.

Diabetic wound healing is severely hindered by a dysregulated microenvironment characterized by hyperglycemia, persistent infection and severe hypoxia. Herein, we designed a pathology-powered therapeutic cascade hydrogel, Gel@Lip-TEx@GCu-GOX based on a dynamic polysaccharide network. This injectable and wound-adaptive carbohydrate polymer matrix not only provides a biocompatible scaffold for irregular wound coverage, but also enables the local retention and stabilization of a tea-exosome/liposome-integrated glucose oxidase catalytic system. Within the dynamic polysaccharide network, glucose oxidase (GOX) initiates hyperglycemia-to-antibacterial conversion by consuming excess glucose and producing antibacterial H2O2, thereby restricting bacterial proliferation and reducing nutrient availability. GHK-Cu further drives H2O2-to-O2 conversion, which prevents peroxide overload, alleviates oxidative injury, and improves the hypoxic wound microenvironment. In parallel, liposome-associated tea leaves-derived exosomes (TEx) protects GOX activity and provides plant exosome-guided immune reprogramming, shifting macrophages toward a reparative M2 phenotype and supporting angiogenesis. In vitro and in vivo studies confirmed that Gel@Lip-TEx@GCu-GOX exerted potent antibacterial activity, enhanced M2 polarization and angiogenesis, and markedly accelerated diabetic wound repair. This study therefore establishes a disease-microenvironment-driven catalytic hydrogel platform for transforming pathological diabetic wound signals into coordinated regenerative therapy.