Chitosan-cellulose hydrogels: advances in stimuli-responsive biomedical therapeutics

Chitosan-cellulose hydrogels have emerged as versatile stimuli-responsive biomaterials for biomedical therapeutics, combining the antimicrobial, mucoadhesive, and pH-sensitive properties of chitosan with the mechanical strength, high water retention, and biodegradability of cellulose. These hybrid systems have demonstrated significant potential in controlled drug delivery, tissue engineering, and regenerative medicine, enabling sustained and localized therapeutic release while reducing systemic toxicity in cancer and chronic disease management. Despite these advantages, important challenges remain regarding long-term in vivo biocompatibility, immune responses, and the biological fate of degradation products, which may influence systemic inflammation and organ function. Furthermore, precise control over multi-stimuli responsiveness, mechanical stability, and degradation kinetics remains critical for clinical translation. Recent advances in nanocomposite strategies, including integration with graphene-based materials, magnetic nanoparticles, and other functional nanomaterials, have introduced next-generation hybrid platforms with enhanced mechanical, electrical, and targeted therapeutic capabilities. Although several preclinical studies have demonstrated promising outcomes, further systematic in vivo investigations and translational research are required to ensure safety, reproducibility, and clinical applicability. This review provides a comprehensive overview of recent advances in chitosan-cellulose hydrogels, critically discusses current limitations, and highlights emerging hybrid systems and future directions toward next-generation biomedical applications.