Copper Nanodots‐Based Hybrid Hydrogels with Multiple Enzyme Activities for Acute and Infected Wound Repair

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.