Heterogeneous zinc/catechol-derived resin microsphere-functionalized composite hydrogels with antibacterial and anti-inflammatory activities promote bacterial-infected wound healing

Bacterial infection in the injured skin may threaten the wound repair and skin regeneration owing to aggravated inflammation. The multifunctional dressings with persistent antibacterial activity and improved anti-inflammatory capability are urgently required. Herein, a type of heterogeneous zinc/catechol-derived resin microspheres (Zn/CFRs) composed of zinc ions (Zn²⁺) and zinc oxide (ZnO) nanoparticles was developed to impart the methacrylamide chitosan (CSMA)-oxidized hyaluronic acid (OHA) hydrogel with a persistent Zn²⁺ release behavior. The Zn/CFRs synthesized via a one-step hydrothermal method exhibited a Zn²⁺-enriched surface and internal ZnO nanoparticles. Owing to the unique microstructure of the microspheres, the Zn/CFRs-functionalized hydrogel (CH-ZnCFR) was able to rapidly release Zn²⁺ in the initial phase and sustain the release of Zn²⁺ for 14 days. Importantly, CH-ZnCFR exhibited excellent anti-inflammatory property by facilitating the macrophage polarization, and also effectively inhibited the growth of <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. In addition, CH-ZnCFR showed excellent self-healing and tissue adhesion properties, and great cytocompatibility by improving fibroblast migration behavior <i>in vitro</i>. Moreover, CH-ZnCFR demonstrated outstanding therapeutic effects in a murine model of <i>S. aureus</i>-infected wounds, including effectively inhibiting bacterial growth, reducing inflammation, increasing the number of M2-type macrophages and facilitating collagen deposition, angiogenesis and tissue regeneration. Therefore, this Zn/CFRs-functionalized composite hydrogel represents a promising strategy for bacterial-infected wound healing and regeneration.