Glucose-responsive dynamic hydrogels from Agastache rugosa polysaccharide for diabetic wound healing.

Abstract

The refractory nature of diabetic wounds stems from persistent hyperglycemia, excessive ROS, and impaired angiogenesis, yet current dressings rely on exogenous factors with bioinactivation and cost limitations. Herein, leveraging the galactose/glucose-rich composition of Agastache rugosa polysaccharide (AP-60-1) bearing cis-vicinal diols, we constructed a dynamic composite hydrogel (CGH) via boronate ester/Schiff base crosslinking, integrating glucose oxidase (GOx) and zinc-humic acid nanoparticles. A key feature is microenvironment-adaptive interfacial enrichment: competitive glucose binding disrupts boronate ester crosslinks under hyperglycemia, increasing network porosity and enhancing BSA adsorption 1.48-fold (p < 0.01), enabling endogenous protein recruitment without exogenous biologics. Combined with injectability, self-healing, and tissue adhesion, CGH achieved 96.5% wound closure by day 14 versus 65% in controls, with complete re-epithelialization and robust neovascularization. The efficacy arises from triple synergy: GOx-mediated glucose depletion generates mild hypoxia to upregulate VEGF; AP-60-1 scavenges ROS for cytoprotection; and GOx-catalyzed H2O2 plus Zn2+ release confers antibacterial activity. This plant polysaccharide-based platform integrates dynamic covalent chemistry with pro-angiogenic remodeling for sustainable diabetic wound repair.