Glucose-Responsive hydrogel optimizing Fenton reaction to eradicate multidrug-resistant bacteria for infected diabetic wound healing

The treatment of infected diabetic wounds faces severe challenges due to vascular deficiencies induced by a hyperglycemia microenvironment and the extensive proliferation of drug-resistant bacteria. In this work, we developed a glucose-responsive hydrogel dressing system (CGH) with dual properties that effectively treat methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in rats and enhance wound healing. The hydrogel is synthesized using copper nanoclusters (CuNCs) cross-linked with oxidized hyaluronic acid (HA-ALD) in situ and decorated with glucose oxidase (GOx). GOx enzymatically degrades excess glucose at the wound site, generating gluconic acid and H2O2, and optimizes the limiting factors of the Fenton reaction. Decreasing pH weakens the interaction between CuNCs and HA-ALD, resulting in the release of CuNCs that catalyze the production of reactive oxygen species (ROS) by degradation of H2O2 through the Fenton reaction. This process can eradicate drug-resistant bacteria. In addition, CuNCs endowed hydrogels with excellent conductivity, thus enabling the promotion of blood vessel formation by electrical stimulation (ES), thereby facilitating tissue repair around the wound area. In conclusion, the developed novel multifunctional wound healing system can conform to irregular wound shapes, reduce glucose levels within the wound, establish a sustained sterile environment, and promote blood vessel formation through electrical stimulation, thus emerging as a highly promising and comprehensive option for effectively treating complex diabetic wounds.