Cu–Fe₃O₄ Nanoclusters-Loaded HAMA Hydrogel Patches for Multifunctional Synergistic Wound Healing

<i>Background</i>: Skin wound healing is a common clinical challenge, facing multiple obstacles including delayed healing, local hypoxia, and bacterial infection, which may lead to prolonged nonhealing or wound infection. Traditional therapeutic strategies mostly intervene in single factors, making it difficult to achieve synergistic effects. Therefore, developing an innovative approach to simultaneously address multiple issues is of great significance. <i>Objective</i>: This study aims to develop a multifunctional hydrogel patch (Cu-Fe₃O₄-loaded HAMA, CFH) by integrating three core functions of promoting healing, supplying oxygen, and antibacterial activity, achieving a "one-for-three" therapeutic effect to provide a more comprehensive solution for wound repair. <i>Methods</i>: Cu-Fe₃O₄ nanoclusters (NCs) were synthesized via a hot solvent method, and CFH hydrogel patches were constructed using molds. In vitro experiments were performed to verify their biosafety, antibacterial properties, and nanozyme activity. A mouse full-thickness skin defect model was established to validate the wound-healing effect of CFH hydrogel patches in vivo. <i>Results</i>: Cu-Fe₃O₄ NCs were successfully synthesized, exhibiting good biocompatibility and significantly promoting the proliferation and migration of human skin fibroblasts (HSFs). Meanwhile, the material showed excellent nanozyme activity, effectively catalyzing the decomposition of hydrogen peroxide and glutathione to remarkably improve local oxygen supply in wounds. Antibacterial experiments confirmed significant inhibitory effects against <i>MRSA</i> and <i>Escherichia coli</i>. In vivo experiments further demonstrated that CFH hydrogel patches adhered well to wounds, enabling rapid, efficient, and aseptic wound healing within 14 days. <i>Conclusions</i>: This study successfully developed a multifunctional CFH hydrogel patch based on Cu-Fe₃O₄ NCs, integrating three functions of promoting cell proliferation, improving oxygen supply, and broad-spectrum antibacterial activity. It provides a safe and efficient novel therapeutic strategy for clinical wound repair, holding important clinical application value.