Chitosan based smart injectable hydrogels for biomedical applications: A comprehensive review

Chitosan-based smart injectable hydrogels (CS-SIHs) have emerged as multifunctional platforms for drug delivery, regenerative medicine, and tissue engineering (TE), owing to their inherent biocompatibility, biodegradability, and responsiveness to external stimuli such as pH, temperature, and ionic strength. These smart hydrogels offer controlled, localized therapeutic release and mimic the extracellular matrix (ECM), thereby fostering cell adhesion, proliferation, and differentiation. In clinical applications such as bone regeneration, cartilage repair, and chronic wound healing, CS-SIHs can be encapsulated with various therapeutic agents, including proteins, nucleic acids, and small molecules, facilitating minimally invasive delivery. Recent studies have been more focused on developing CS-SIHs with enhanced bioactivity, mechanical integrity, and adaptability to dynamic microenvironments. This review provides an in-depth analysis of novel CS-SIH formulations and their potential therapeutic applications, as well as a comprehensive overview of recent preclinical and translational studies. Additionally, this investigation explores the challenges of clinical translation, including regulatory hurdles and scalability concerns. This work distinguishes itself by systematically integrating the physicochemical properties, intelligent response mechanisms, crosslinking strategies, and biomedical applications of CS-SIHs, offering a coherent framework for future research and development in the field of biomedical engineering.