Injectable curdlan-derived hydrogel with differential release of copper and zinc ions for synergistic therapy of infected wounds.

The engineering of multifunctional injectable hydrogels that dynamically address phase-specific requirements during infected wound healing represents a pivotal challenge in advanced wound care. Here, a series of carboxymethyl-modified curdlan (CRc)-based hydrogels were developed via multiple physical interactions with divalent metal ions. Specifically, the carboxyl groups on the CRc molecular chains formed dynamic bonds with Cu2+, Zn2+, and Ca2+, effectively facilitating hydrogel formation. These composite systems demonstrated rapid gelation (within 2 min), outstanding injectability, good self-healing ability, suitable tissue adhesion properties, and distinct release behaviors of various ions. In vitro experiments demonstrated that the Cu/Zn@CRc system exhibited dual-phase therapeutic efficacy: the initial rapid release of Cu2+ achieved potent antibacterial and biofilm-disruption capabilities while also promoting macrophage recruitment and enhancing microbial clearance. Subsequent sustained Zn2+ release orchestrated anti-inflammatory responses, efferocytosis potentiation, and macrophage polarization toward regenerative phenotypes. In staphylococcus aureus - infected acute and diabetic wound models, Cu/Zn@CRc hydrogel accelerated infection control while synchronously mitigating inflammation and promoting tissue regeneration through demand-driven ion delivery. Histological analyses confirmed enhanced collagen deposition and neovascularization. In conclusion, this study not only developed a novel CRc-based hydrogel carrier system for treating infectious wounds but also established a simple and efficient manufacturing procedure for CRc composite hydrogels.