Copper peroxide nanozyme-loaded hydrogel: A new approach for antibacterial and regenerative wound healing

• Disulfide-crosslinked hyaluronic acid hydrogel integrated with copper peroxide nanozymes. • Hydrogel combines adhesion, self-healing, and moisture-retention properties. • Multifunctional material accelerates bacterial clearance and wound tissue regeneration. Treating chronic infected wounds is challenging due to persistent bacteria, low oxygen levels, and poor tissue regeneration. Conventional antibacterial dressings struggle to eliminate bacteria effectively while supporting a healing environment. This study accordingly developed a nanozyme-enabled antibacterial hydrogel by integrating copper peroxide nanozymes into a thiol-modified hyaluronic acid network (CuO 2 /HA-SH gel). First, the disulfide-crosslinked hydrogel was shown to provide strong tissue adhesion, high water retention, and self-healing capability, enabling stable immobilization of nanozymes at wound sites. Next, under mildly acidic wound conditions, the incorporated CuO 2 nanozymes exhibited pronounced peroxidase-like catalytic activity, generating reactive oxygen species (ROS) and releasing Cu 2+ ions. Furthermore, the synergistic action of ROS-mediated oxidative stress and copper-induced cuproptosis-like process resulted in efficient bacterial eradication. In vitro evaluations demonstrated significant antibacterial efficacy, favorable cytocompatibility, and enhanced hemostatic performance. Finally, in vivo experiments using a full-thickness Staphylococcus aureus -infected wound model confirmed accelerated wound closure, reduced inflammation, increased collagen deposition, and promoted epidermal regeneration. Therefore, the CuO 2 /HA-SH hydrogel represents a multifunctional nanozyme-based dressing that integrates catalytic antibacterial therapy with regenerative support, offering a promising material strategy for advanced infected wound management.