Tunable Functional Chitosan-PEGn Hydrogel for Microenvironment-Responsive Antibacterial and Wound Healing Applications

As a physiological process maintaining skin integrity, wound healing is often disrupted by complex microenvironments, infection, and abnormal pH levels, leading to delayed healing. Additionally, irregularly shaped wounds are complex enough to cover adequately with traditional dressings. To address these issues, we developed a functional hydrogel via the Schiff base reaction between chitosan (CS) and difunctional telechelic-polyethylene glycol (DT-PEGn) of varying molecular weights, which was subsequently loaded with ciprofloxacin (CIP) to form a CS@DT-PEGn@CIP composite system. The results demonstrate that DT-PEGn of different molecular weights effectively modulate the hydrogel's swelling ratio, mechanical properties, injectability, self-healing capacity, and drug release characteristics, thereby conferring tunable functional advantages in wound repair. In vitro antibacterial assays and a rat full-thickness wound model further confirmed the outstanding efficacy of CS@DT-PEGn@CIP in significantly inhibiting bacterial growth and accelerating wound healing. Notably, the CS@DT-PEG6000 hydrogel containing only one-third of the free CIP dose exhibited superior therapeutic outcomes compared to free CIP alone, highlighting the high efficiency and safety of the composite system. In summary, this study systematically demonstrates the unique advantages of CS@DT-PEGn hydrogel in promoting wound healing, including its responsiveness to microenvironmental pH, antibacterial properties, and excellent conformability to wound surfaces. These findings provide novel strategies and potential applications for clinical wound management.