Antibacterial reuterin as a multifunctional crosslinker for constructing chitosan-based hydrogels to promote infected wound healing

Compared to traditional antibiotics, which often contribute to antibiotic resistance, probiotics and their metabolites have garnered increasing attention for their potential to improve the wound microenvironment. Among these, reuterin, a metabolite produced by Limosilactobacillus reuteri , exhibits notable antioxidant and antimicrobial activities, making it particularly advantageous for medical applications. Inspired by the structural similarity of reuterin to conventional chemical crosslinkers, we explored its dual role for the first time—as both a bioactive component and a crosslinking agent—by combining it with chitosan to develop a novel therapeutic hydrogel, eliminating the need for additional drug loading. At an optimal reuterin-to-chitosan molar ratio of 1:2, the hydrogel demonstrated outstanding performance. Cytotoxicity assays confirmed its safety, with a hemolysis rate below 2 %, indicating excellent biocompatibility. Remarkably, the hydrogel achieved an impressive 99 % antibacterial efficacy and over 60 % DPPH radical scavenging capacity in vitro. In a rat model of infected wounds, the hydrogel exhibited acid-responsive release of reuterin, effectively suppressing bacterial proliferation. These combined effects significantly accelerated wound healing, demonstrating an approximately 10 % improvement in healing rates compared to commercial controls. In conclusion, the reuterin-crosslinked chitosan hydrogel represents a promising, safer and more effective alternative to traditional chemical crosslinked hydrogels for clinical wound management.