Nir-enhanced HCuS-Pt nanozymes based hydrogel dressing accelerates chronic infected wound healing via synergistic antibacterial, antioxidant, and immunomodulatory activities

• The loading of ultrasmall Pt NPs enables HCuS to achieve a strategy of “killing two birds with one stone”. • HCuS-Pt nanozyme composite hydrogel showed great injectability, self-healing and adhesion properties. • HCuS-Pt nanozyme composite hydrogel exhibited an anticipated multi-dimensional regulation of the wound immune microenvironment. • HCuS-Pt nanozyme composite hydrogel showed considerable effect for accelerating the healing of chronic wounds infected with S. aureus . Chronic infectious wounds often delayed in healing due to their complex pathogenic factors. Currently, multifunctional hydrogel dressings offer a cost-effective and efficient therapeutic strategy to accelerate chronic wound healing by overcoming healing barriers. In this study, a multifunctional hydrogel named HOCP2 was developed by incorporating ultrasmall platinum (Pt) nanoparticles-loaded hollow HCuS (HCuS-Pt) nanozymes into a hydrogel matrix composed of adipic acid dihydrazide modified hyaluronic acid (HA-ADH) and oxidized sodium alginate (OSA), which were crosslinked via Schiff base bonds. The loading of ultrasmall Pt NPs reduced the bandgap of HCuS, achieving a dual-plasmonic synergistic enhancement effect that further improved photothermal performance, and synergistically enhanced the ability to scavenge ROS. Moreover, HOCP2 hydrogel exhibited favorable injectability, self-healing and adhesive properties. In vitro experiments demonstrated that HOCP2 hydrogel had reliable biocompatibility, could promote cell migration and enhance angiogenesis. Additionally, it exhibited antioxidant and anti-inflammatory properties while promoting M2 macrophage polarization, thereby modulating the wound immune microenvironment. The HOCP2 hydrogel also demonstrated photothermal antibacterial effects against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). In vivo studies further certificated its ability to accelerate infectious wound healing. In conclusion, HOCP2 hydrogel dressing shows significant potential for application in the treatment of chronic infectious wounds.