Triple-Responsive Hydrogel Integrating Polyphenol-Metal Activity for Infected Diabetic Wound Therapy

Infected diabetic wounds remain a major clinical challenge owing to the complex pathological microenvironment characterized by persistent bacterial infection, excessive reactive oxygen species (ROS), prolonged inflammation, and impaired angiogenesis. Herein, we report a triple-responsive, injectable, adhesive, and self-healing hydrogel (RCGel) designed to dynamically regulate the diabetic wound microenvironment and promote efficient tissue regeneration. RCGel was constructed through reversible Schiff-base and boronate-ester cross-linking between CMCS-PBA and OChS-DA and was incorporated with rosmarinic acid-cerium nanoparticles. RCGel exhibited a sustained and potent ROS-scavenging capability. Meanwhile, RCGel enabled on-demand photothermal antibacterial therapy under mild near-infrared irradiation, effectively eradicating MRSA and P. aeruginosa. In vitro studies demonstrated excellent cytocompatibility, reduced intracellular ROS levels, macrophage M2 polarization, and enhanced angiogenic potential. In vivo, RCGel significantly accelerated wound closure, suppressed infection and inflammation, promoted neovascularization and collagen deposition, and improved tissue remodeling in both diabetic noninfected and MRSA-infected wound models, without evident systemic toxicity. Overall, this work presented a microenvironment-adaptive multifunctional hydrogel dressing that integrated antibacterial, antioxidative, immunomodulatory, and pro-regenerative functions, offering a promising therapeutic strategy for infected diabetic wound treatment.