Functional biocompatible chitosan hydrogels crosslinked with a vanillin isomer: Controlled antioxidant, antimicrobial, and self-healing properties.

This study reports the synthesis of sustainable, ecofriendly chitosan-based hydrogels through crosslinking with 4-methoxysalicylaldehyde, a vanillin isomer, highlighting their potential as bioactive biomaterials with antimicrobial and antioxidant properties. The main objective was to prepare and evaluate the hydrogels activity in terms of cytotoxicity, antimicrobial and antioxidant activity, and self-healing and swelling behavior. Characterization via NMR, FTIR, XRD, and POM confirmed the formation of imine linkages and intermolecular forces, indicating that the hydrogelation of chitosan with 4-methoxysalicylaldehyde takes place by both chemical and physical interactions, resulted porous structures with significant swelling capacities of 145 g/g in water and 25 g/g in PBS (pH 7.4). Rheological analysis demonstrated crosslinking-dependent mechanical properties, transitioning from a solid-like to a liquid-like behavior with increasing crosslinker ratios. The incorporation of 4-methoxysalicylaldehyde resulted in a significant increase in antioxidant activity, rising from 22 % to 51 %. Moreover, the hydrogels exhibited selective and effective antimicrobial activity, particularly against Candida albicans, and showed progressive biodegradation with up to 34 % mass loss over 21 days. MTT assays confirmed their lack of toxicity against normal human fibroblast over 48 h. All these findings suggest that these chitosan-based hydrogels hold significant promise for various biomedical applications.