pH-responsive PAM/Gel/QCS drug-loaded hydrogel with self-healing and antimicrobial properties

Natural polysaccharide polymer hydrogels have garnered significant attention in biomedical applications due to their exceptional biocompatibility and biodegradability. However, their practical utility is constrained by inherent limitations such as inadequate mechanical strength and poor toughness. These deficiencies often result in premature drug release and reduced functional longevity when applied in drug delivery systems. To address these challenges, the incorporation of self-healing systems based on dynamic covalent or non-covalent bonds has emerged as an effective solution. In this study, chitosan (CS) was first quaternized (marked as QCS) and then compounded with gelatin and polyacrylamide, using 5-fluorouracil (5-Fu) as the model drug. The Fe³⁺@ TA system, formed by adding Fe³⁺and TA, served as a redox initiator to enable free radical polymerization of acrylamide and shorten the preparation time of hydrogel. Ultimately, a smart hydrogel with an interpenetrating network structure was successfully prepared. By adjusting the concentrations of CS and TPP, the regulation of the microstructure and physicochemical properties of the hydrogel was achieved. The results showed that the hydrogel, as a candidate multifunctional dressing, possessed excellent tensile and compressive properties, self-healable capability, and appropriate repeatable adhesion performance. In vitro drug release and antimicrobial assays demonstrated that the hydrogel exhibits pH-responsive release characteristics and effective antimicrobial properties against Staphylococcus aureus and Escherichia coli. Comprehensive biocompatibility assessments, including cytotoxicity and hemolysis testing, confirmed the material's biological safety profile. These findings collectively establish the strong and flexible composite hydrogel as a promising platform with extensive potential for drug delivery applications.