Thermosensitive Hydrogel Loaded with Nickel–Copper Bimetallic Hollow Nanospheres with SOD and CAT Enzymatic-Like Activity Promotes Acute Wound Healing

Various injury defense and repair functions are performed by the skin. Free radicals secreted after injury cause oxidative stress and inflammatory responses, which make wound healing difficult. However, the current metal nanomaterials for wound repair do not have sufficient catalytic activity or complex material design and cannot properly fit wounds. Therefore, it is imperative to develop more effective therapeutic approaches. This study investigated the effect of Ni₄Cu₂ hollow nanospheres composited with F127 hydrogel on promoting wound healing by applying them to wounds. Ni₄Cu₂ hollow nanospheres exhibited a superior spatial structure, contained many catalytic sites, and could be synthesized in a simple manner. In vitro experiments showed that Ni₄Cu₂ hollow nanospheres had superoxide dismutase-like activity and promoted fibroblast migration, angiogenesis, and macrophage polarization. F127, which is a thermosensitive, nontoxic, phase-change and porous hydrogel material, has proven to be an effective choice for injectable and sprayable medical dressings. Ni₄Cu₂ hollow nanospheres were mixed with F127 hydrogel without significantly affecting its performance. In addition to adapting to the complex, irregular gaps of acute wounds, the mixture lengthened the nanozyme release time, which enhanced healing. Based on the animal experiments, the Ni₄Cu₂/F127 composite hydrogel effectively promoted wound healing, epithelial regeneration, and the formation of skin appendages such as hair follicles in mice. Furthermore, the Ni₄Cu₂/F127 composite hydrogel was nontoxic to animals and had high biological safety. The Ni₄Cu₂/F127 composite hydrogel has provided an innovative strategy to develop composite hydrogels for the treatment of acute skin wounds.