Zr-MOF CascadeNanoreactor Accelerates Chronic DiabeticWound Healing via Angiogenesis and Microenvironment Remodeling

Persistent hyperglycemia and alkaline microenvironments in chronic diabetic wounds promote bacterial resistance, continuous inflammation, and delayed wound repair. Herein, a thermosensitive hydrogel, integrating zirconium-based metal-organic framework (Zr-MOF)-loaded glucose oxidase (GOx) nanozyme and l-arginine (l-Arg), is developed for diabetic wound microenvironment remodeling and moist healing. Upon encountering glucose, GOx neutralizes hyperglycemia, producing gluconic acid to lower the wound pH and generating hydrogen peroxide (H2O2). The resulting acidic wound environment activates the peroxidase (POD)-like activity of Zr-MOFs, generating highly toxic hydroxyl radicals that eliminate bacterial biofilms. The excess H2O2 drives the conversion of l-Arg into nitric oxide, preventing excessive reactive oxygen species accumulation and promoting angiogenesis, epithelialization, and collagen deposition. Experiments demonstrate that the prepared hydrogel effectively reverses both the alkaline pH and hyperglycemia conditions characteristic of diabetic wounds, significantly accelerating the healing of bacteria-infected chronic diabetic wounds and providing an approach for chronic wound management.