Green Functionalization of Chitosan via Multicomponent Reactions: Unlocking New Horizons in Biomedical Materials

This review presents recent progress in the functionalization of chitosan (Cs) through multicomponent reactions (MCRs) as a promising route for creating innovative biofunctional materials for biomedical applications. Owing to its inherent biocompatibility, biodegradability, and chemical adaptability, Cs serves as an excellent platform for engineering responsive and multifunctional biomaterials. The application of diverse MCRs, such as Ugi, Mannich, [3 + 2] cycloaddition, and Debus reactions, has enabled the synthesis of Cs-based composites with improved antibacterial, anticancer, drug delivery, antimicrobial, antifungal, pH-responsive, and UV-shielding capabilities. These chemical alterations not only facilitate the precise adjustment of physicochemical characteristics but also bolster structural stability in physiological environments and enhance targeted therapeutic efficacy. Although there has been considerable research on Cs, its direct functionalization through MCRs is still relatively unexamined, presenting a sustainable and highly adaptable approach for the development of sophisticated bioengineered systems. By integrating green multicomponent chemistry with Cs-based platforms, this review provides both a conceptual framework and practical insights to guide future developments in bioresponsive biomedical materials.