Enzyme hybrid virus-like hollow mesoporous CuO adhesive hydrogel spray through glucose-activated cascade reaction to efficiently promote diabetic wound healing

Diabetic wounds characterized by impaired healing due to uncontrolled and interrelated bacterial infection, reduced vascularization and hypoxia microenvironment, remain a worldwide challenge. Copper ions have been proved to stimulate angiogenesis to improve chronic wound healing, and copper oxide nanoparticles have been widely investigated for bacterial elimination. Herein, we constructed an adhesive hydrogel spray with loading glucose oxidase hybrid virus-like hollow mesoporous CuO nanospheres to efficiently promote diabetic wound healing. Under local hyperglycemia in bacterial biofilm, CuO nanospheres can be decomposed to convert the glucose degradation, produce H2O2 to generate toxic •OH for antibacterial usage, then the simultaneously released Cu2+ can induce the proliferation and migration of keratinocytes and tubule formation of endothelial cells. More importantly, after bacterial eradication within inflammatory phase of wound healing, CuO nanospheres can act as catalase-mimic agents to produce massive O2 by catalyzing intracellular H2O2 for hypoxia alleviation. This glucose-activated cascade reaction hydrogel spray can efficiently promote diabetic wound healing, which might provide a reliable tool for synergistic reconstruction of the chronic non-healing wounds.