In situ injectable self-healing hydrogel of 5-fluorocytidine-modified chitosan with antifungal and antibacterial properties for promoting wound healing.

Current research on antibacterial hydrogel dressings remains predominantly focused on bacterial pathogen management, while facing technical bottlenecks in constructing synergistic antifungal therapeutic systems. The limitations of this narrow antimicrobial spectrum pose significant clinical challenges, particularly pronounced in burn wound management characterized by pathological healing microenvironments. Notably, existing biomaterials exhibit dual deficiencies when addressing polymicrobial infections: neither capable of mitigating antibiotic resistance risks nor equipped with active tissue regeneration modulation capabilities. More importantly, injectable self-healing adhesive dressings demonstrate remarkable advantages through their unique dynamic adaptability - enabling in situ filling of irregular wound cavities to maintain a sealed therapeutic environment, while achieving functional self-recovery following mechanical damage. These properties prove pivotal for enhancing dynamic repair efficacy in burn wound treatment. In this study, five distinct water-soluble derivatives of 5-fluorouracil-modified chitosan (5FC-CS) were synthesized, each with degrees of substitution (DS) ranging from 0.006 to 0.16. The resulting AgNPs-loaded 5-fluorouracil-modified chitosan solution was then reacted with an 8-arm-PEG-CHO solution, facilitating the formation of AgNPs-loaded 5-fluorocytidine-modified chitosan composite hydrogels (Ag@5FC-CS/PEG) through a Schiff base reaction. These hydrogels exhibit key properties including in situ injectability, rapid self-healing capabilities, favorable biocompatibility, strong hemostatic function, and significant antifungal and antibacterial activity. Notably, the hydrogel demonstrates a 100 % antifungal efficacy against C. albicans and a complete antibacterial effect against both S. aureus and E. coli. In animal model, the application of Ag@5FC-CS/PEG hydrogels led to a reduction in inflammatory cell infiltration, enhanced vascular formation, increased collagen deposition, and promoted more rapid regeneration of epithelial tissue. Thus, the AgNPs-loaded 5-fluorouracil-modified chitosan composite hydrogel holds great potential for medical applications in the treatment of burn wounds.