Infection-adaptive polysaccharide hydrogels integrating ginsenoside Rb1@ZIF-8 nanozyme for diabetic wound healing

Diabetic wound management remains a major challenge in regenerative medicine because hyperglycemia disrupts immune homeostasis and delays tissue reconstruction. Persistent bacterial colonization, excessive oxidative stress, and prolonged inflammation synergistically prevent diabetic wounds from transitioning from the inflammatory stage to effective repair. However, current dressings rarely coordinate early infection control with sustained microenvironment regulation required for complete regeneration. Here, we show an infection-adaptive polysaccharide hydrogel dressing (ADR1) constructed via dynamic Schiff-base crosslinking and integrated with ginsenoside Rb1-loaded copper-doped ZIF-8 nanozymes (Rb1@ZIF-8). In an acidic infectious milieu, ADR1 enables controlled nanozyme release and catalytic generation of bactericidal reactive oxygen species, achieving near-complete killing of Staphylococcus aureus and Escherichia coli, while the subsequent Rb1 release enhances antioxidation and immunomodulation, improving fibroblast survival under oxidative stress. Furthermore, ADR1 markedly accelerates healing in an infected diabetic wound model, with the residual wound area reduced to 7.3% of the control group by day 14, accompanied by suppressed bacterial survival (2.7%) and inflammatory signalling and enhanced angiogenesis. Collectively, ADR1 offers a staged, antibiotic-free strategy integrating antibacterial, antioxidative, anti-inflammatory, and pro-angiogenic functions for comprehensive therapy of infected diabetic wounds.