Vanillin-grafted chitosan biopolymers via nucleophilic addition-elimination: A promising bioactive biopolymer for enhanced skin wound repair.

Enhancing the antimicrobial and antioxidant properties of biomaterials remains a central goal in the development of advanced bioactive scaffolds for biomedical applications. In this study, we present a novel strategy for introducing vanillin moiety into chitosan via its coupling to ethyl (Z)-2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate (V2), yielding a series of chitosan-functionalized biopolymers designated as CSV50, CSV100, and CSV200 with degrees of substitution 66.8, 72.4, and 74.5%; respectively. Structural characterization confirmed the successful grafting of V2 onto the CS backbone. While scanning electron microscopy demonstrated the formation of well-interconnected, porous network architectures. These new functionalized chitosan biopolymers exhibited a notable decrease in dynamic viscosity and improved antioxidant and antimicrobial activities. The cytocompatibility assays using human fibroblast skin cells (HFB-4) endorsed their safety, and both CSV100 and CSV200 accelerated in vitro wound closure. In vivo wound healing study using male albino rats further demonstrated that treatment with CSV100 or CSV200 led to a substantial reduction in wound area, with wound closure efficiency of 94.25%. Histological analysis suggested that CSV200-treated groups exhibited the highest levels of collagen deposition, granulation tissue formation, and minimal inflammatory response. Collectively, these findings highlight CSV200 as a promising candidate for wound healing applications, offering enhanced bioactivity and structural performance.