Adaptive injectable pullulan/carboxymethyl chitosan hydrogel accelerates diabetic wound healing through antibacterial, angiogenic, and immunomodulatory effects.

Persistent inflammation, bacterial infection, and insufficient angiogenesis are key factors contributing to delayed wound healing in diabetic patients, making the suppression of inflammatory responses, control of bacterial proliferation, and promotion of angiogenesis essential strategies for enhancing diabetic wound repair. In this study, we developed a multifunctional adaptive injectable hydrogel (PCCCu) composed of dynamically crosslinked polymers incorporating curcumin and copper oxide nanoparticles to accelerate diabetic wound healing. Results demonstrate that the hydrogel network, formed via Schiff base reactions between oxidized pullulan and carboxymethyl chitosan, effectively adheres to irregular wounds while maintaining structural stability. In vitro evaluations confirmed that the PCCCu hydrogel exhibits excellent biocompatibility (hemolysis rate < 5 %), significant antibacterial activity (antibacterial rate exceeding 90 %), robust pro-angiogenic capacity, and the ability to modulate inflammatory responses through macrophage polarization. In vivo experiments further verified that the PCCCu hydrogel significantly accelerates wound healing in diabetic rat models by promoting epithelialization, increasing granulation tissue formation, enhancing vascular regeneration, and regulating collagen arrangement. In conclusion, this self-adaptive injectable multifunctional hydrogel demonstrates promising potential for clinical application in diabetic wound therapy due to its synergistic therapeutic effects.