Beta‐glucan modification and incorporation of peptide for infected wound healing applications

Abstract Hydrogel dressings, known for their breathability and hygroscopic properties, have garnered significant attention in the field of bioactive wound care. Among them, hydrogels composed of polysaccharides and peptides offer superior biocompatibility, intrinsic antibacterial properties, and the ability to mimic the extracellular matrix. In this study, we developed hybrid hydrogels, BAA/C 8 G 2 , BAA/G 3 , and BAA/c(KW), by crosslinking immunomodulatory β‐glucan derivatives with antimicrobial peptides via enamine bonds. These hydrogels exhibited enhanced mechanical strength compared to those crosslinked with oxidized β‐glucan through imine bonding, alongside pH responsiveness and controlled drug release behavior. The hydrogels demonstrate broad‐spectrum antibacterial activity against both Gram‐positive and Gram‐negative bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA), and maintain sustained inhibition of Escherichia coli for over 10 days. Furthermore, they displayed excellent in vitro biocompatibility and effectively promoted fibroblast cell migration. The results highlight the potential of enamine‐linked polysaccharide–peptide hybrid hydrogels as promising candidates for bacterial‐infected wound treatment. Highlights Acetoacetyl β‐glucan crosslinked with AMPs via dynamic enamine bonds. The BAA‐peptide hydrogels demonstrated improved mechanical properties. The pH‐responsive enamine bonds enabled controlled release of AMPs. The hydrogels exhibited sustained antibacterial activity. The hydrogels are biocompatible and promote cell migration.