Chitosan-Based Thermosensitive Hydrogel Loaded with Quercetin Inclusion Compound for Accelerating Infectious Wound Healing

Background: Chitosan-based hydrogels exhibit excellent temperature-sensitive properties and are widely used as skin dressings. However, several challenges remain, such as long gelation times and difficulties releasing insoluble drugs, which limit their application in skin wound healing. In this study, we developed a novel sulfobutyl-β-cyclodextrin/quercetin@chitosan/hyaluronic acid hydrogel (Qe/SBE@CS/HA Gel). In this gel, SBE not only encapsulates Qe to form inclusion complexes, thereby enhancing the solubility of Qe, but also shortens the gelation time of thermosensitive gels through electrostatic adsorption with chitosan. Methods: Qe/SBE was prepared using the saturated solution method, while Qe/SBE@CS/HA gel was fabricated via electrostatic adsorption. The performance of the gels was evaluated using antibacterial, antioxidant, compatibility, and skin infection damage models. Results: The Qe/SBE@CS/HA Gel exhibits both thermosensitivity and acid sensitivity, releasing 91.9% of Qe in a medium with a pH of 5.0. This gel displays notable antibacterial activity and antioxidant characteristics. Furthermore, it shows excellent biocompatibility, as evidenced by hemolytic and in vivo degradation tests. The gel has the capacity to modulate chronic inflammation and facilitate angiogenesis and collagen synthesis, thereby significantly accelerating wound healing in wound and infection models. Conclusions: This multi-responsive and multifunctional gel shows potential as a therapeutic strategy for bacterial infection wounds.