Design and characterization of a ROS-responsive antibacterial composite hydrogel for advanced full-thickness wound healing

Full-thickness skin wounds remian a significant and pressing challenge. In this study, we introduce a novel composite hydrogel, CS + GA + Zn-HA. This hydrogel is formulated by incorporating 1 % (1 g/100 mL) of bioactive Zinc-substituted hydroxyapatite nanoparticles (Zn-HA) and 0.2 % (0.2 g/100 mL) of Gallic acid (GA) into chitosan (CS) hydrogels. A 56 % (3-glycerophosphate sodium ((3-GP) solution serves as the cross-linking agent, and the hydrogel is formed at 37 degrees C. This composite hydrogel can effectively modulate the wound microenvironment, facilitating comprehensive skin wound healing within two weeks. Physicochemical characterization demonstrates that this hydrogel is thermosensitive, with remarkable swelling behavior, mechanical strength, and drug-delivery performance. In vitro, the GA-incorporated hydrogels possess outstanding reactive oxygen species (ROS) scavenging and antioxidant properties, protecting L929 cells from hydrogen peroxide- induced oxidative damage. The combination of Zn-HA nanoparticles and GA not only augments the functionality of the hydrogel and decreases its degradation rate but also enables the controlled release of curcumin. Moreover, it provides a suitable immune microenvironment in terms of biological effects and significantly boosts the hydrogel's antibacterial ability, as demonstrated by an 89.2 % reduction in E. coli and a 53.6 % reduction in S. aureus. Benefiting from these properties, the CS + GA + Zn-HA composite hydrogel significantly promotes granulation tissue formation, re-epithelialization, angiogenesis, and wound closure in vivo. In conclusion, our research highlights the potential of the CS + GA + Zn-HA hydrogel as a multifunctional scaffold in tissue engineering, providing valuable insights for the design of future wound dressings for diverse wound types.