Cu–CeO2 NP-loaded HAMA hydrogel patches for promoting high-quality cutaneous wound healing

Abstract

Background Wound healing is a common issue in dermatology and plastic surgery practice and is jointly regulated by multiple factors, including cell proliferation, inflammatory responses, oxidative stress, bacterial infection, and tissue remodeling. Complex wounds still face challenges such as delayed repair, persistent inflammation, increased infection risk, and scar formation, while conventional treatments are difficult to achieve coordinated intervention across multiple stages. Therefore, developing biomaterials with pro-repair, anti-inflammatory, antibacterial, and healing quality-improving functions is of great significance. Objective This study aimed to construct a Cu–CeO2 nanoparticle (NP)-loaded hyaluronic acid methacrylate composite hydrogel patch, named Cu–CeO2-loaded HAMA (CCH), to improve the wound repair microenvironment and promote high-quality wound healing through multifunctional synergistic effects. Methods Cu–CeO2 NPs were synthesized using a hydrothermal method and loaded into HAMA hydrogel to prepare CCH hydrogel patches. In vitro experiments were performed to evaluate their biocompatibility, cell proliferation- and migration-promoting abilities, antioxidative/anti-inflammatory properties, nanozyme activity, and antibacterial effects. Meanwhile, a mouse full-thickness skin wound model was established to further verify the in vivo wound healing-promoting efficacy of CCH hydrogel patches. Results Cu–CeO2 NPs and CCH hydrogel patches were successfully prepared. In vitro results showed that Cu–CeO2 NPs exhibited favorable biocompatibility, promoted fibroblast proliferation and migration, enhanced endothelial cell viability, and facilitated macrophage polarization toward the M2 phenotype. In addition, these NPs exhibited reactive oxygen species (ROS)-scavenging capacity and hydrogen peroxide (H2O2) decomposition-mediated oxygen generation ability, and markedly inhibited methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). In vivo results further demonstrated that CCH hydrogel patches accelerated wound closure, improved healing quality, and attenuated scar-like changes in mice. Conclusion This study developed Cu–CeO2 NP-loaded CCH hydrogel patches that can synergistically regulate the wound microenvironment through multiple effects, including pro-repair, antioxidative/anti-inflammatory, antibacterial, and tissue remodeling-improving activities, providing a promising biomaterial strategy for high-quality repair of complex skin wounds.