Microenvironment-responsive releasing copper-tannic acid coordination nanozyme and recombinant human collagen type III hydrogel for accelerating infection wound repair.

Abstract

Infected wounds with bacterial biofilms remain a clinical challenge due to persistent inflammation, excessive reactive oxygen species (ROS), and insufficient therapeutic functions of conventional dressings. Current pH-responsive hydrogels suffer from mismatched degradation and limited microenvironment regulation, while free nanozymes or recombinant collagen alone cannot address the complex wound healing cascade. Herein, a bacterial infection microenvironment-responsive hydrogel (CuTA/rHCIII@Hydrogel) was developed by incorporating copper-tannic acid coordination (CuTA) nanozyme and recombinant human type III collagen (rHCIII) into an oxidized dextran/gelatin matrix formed via dynamic Schiff base bonds. The hydrogel exhibited injectability, self-healing, and acidic pH-responsive degradation. In the acidic infected wound microenvironment, the hydrogel could responsively degrade by simultaneously release CuTA and rHCIII. CuTA nanozyme exerted excellent antibacterial effects through disrupting bacterial membranes, inducing intracellular copper ion stress, and causing DNA damage. Meanwhile, CuTA possessed superoxide dismutase- and catalase-mimicking activities to efficiently scavenge ROS, thereby alleviating oxidative stress and promoting M2-type macrophage polarization. The released rHCIII synergistically enhanced cell migration and upregulates CD31 and vascular endothelial growth factor (VEGF) to promote angiogenesis. Leveraging its combined antibacterial, anti-inflammatory, microenvironment-remodeling, and pro-regenerative capabilities, the CuTA/rHCIII@Hydrogel markedly accelerated the repair of infected wounds, establishing it as a promising platform for treating refractory infected wounds.