Promotion of diabetic wound healing using novel Cu2O/Pt nanocubes through bacterial killing and enhanced angiogenesis in rats

Chronic bacterial infection, local inflammation, and insufficient angiogenesis contribute to poor healing of diabetic wounds. Here, Cu2O/Pt nanocubes (CPN) are successfully developed with good biocompatibility for treatment of diabetic wounds in rats. The synthesized CPN are characterized using SEM, XPS, and XRD. CPN exhibit triple-enzyme mimetic activity: oxidase-like, peroxidase-like, and catalase-like activities. Moreover, CPN show significant antibacterial activity against Gram-negative and Gram-positive bacteria when combined with low concentration of H2O2, via generation of highly reactive ROS. CPN also exhibit significantly accelerated wound healing in a full-layer deprivation rat model infected by Staphylococcus aureus, which is ascribed to the constant release of copper ions, subsequently activating the VEGF/AKT/ERK1/2 signaling pathway and promoting angiogenesis. CPN are able to catalyze H2O2 to generate O2 for local hypoxia alleviation. Furthermore, in vivo results indicate that treatment with CPN promotes the expression of transforming growth factor and matrix metalloproteinases, causing enhanced cell proliferation and collagen deposition, as well as extracellular matrix remodeling. In contrast, CPN decrease the expression of proinflammatory cytokines, such as TNF-ɑ and IL-1β, which are induced by bacterial infection and hyperglycemia. These results suggest a novel strategy for the treatment of diabetic wound healing.