Chitosan-Based Thermosensitive Hydrogel Codelivering Berberine and Resveratrol Promotes Wound Healing of Bacterial Infection in Diabetic Mice

Diabetic bacterial infected wounds are severe complications in diabetic patients, posing significant challenges to clinical management. The wound site is prone to bacterial colonization and biofilm formation, triggering a persistent inflammatory response and forming a vicious cycle of “hyperglycemia−infection−inflammation”. Therefore, the development of antibacterial materials that are efficient, safe, and less likely to induce drug resistance is of great significance for improving wound repair. In this study, a thermosensitive composite hydrogel based on chitosan (CS) and poloxamer (P407/P188), named CPP, was developed for the codelivery of berberine (BBR) and resveratrol (RES). This system undergoes a phase transition at physiological temperature to form a porous network structure, enabling controllable and sustained drug release. In vivo experiments using a diabetic mouse model with infected wounds showed that the CPP@BBR@RES hydrogel effectively inhibited bacterial colonization, alleviated the inflammatory response, and significantly promoted collagen deposition, angiogenesis, and wound closure. This study innovatively combines the thermogelling and sustained-release properties of the material with the synergistic antibacterial, anti-inflammatory, and repair-promoting functions of the dual drugs, providing a multifunctional integrated therapeutic strategy for diabetic infected wounds.