Abstract
Because of their tissue-conforming qualities, in situ gelation, and less invasive distribution, injectable hydrogels (IHs) have become a revolutionary class of soft materials with enormous potential in biomedical applications. The ability of stimuli-responsive polymer-derived smart injectable hydrogels (SIHs) to react dynamically to external stimuli like temperature, redox potential, pH, or enzyme activity has drawn more attention than any other. This responsiveness enables precise spatiotemporal control over therapeutic delivery, tissue regeneration, and self-healing capabilities. Recent advances in cross-linking strategies, including reversible covalent and supramolecular interactions, have expanded the design space for SIHs, enhancing their adaptability to dynamic physiological environments. With an emphasis on structure-property connections, rheological behavior, dynamic cross-linking mechanisms, and stimuli-triggered transitions, we provide a thorough summary of the basic ideas guiding the injectability and functioning of SIHs in this review. From biosensing and regenerative medicine to tissue engineering and cancer treatment, we critically analyze the most recent advancements in their biomedical applications. Despite substantial progress, challenges such as mechanical fragility, limited biodegradability, cytotoxicity concerns, and scalability remain significant barriers to clinical translation. This review also highlights emerging strategies such as bioinspired polymer design, modular cross-linking architectures, and scalable fabrication methodologies aimed at overcoming current limitations. By bridging fundamental material design principles with translational objectives, we provide an integrated perspective to guide the development of next-generation smart injectable hydrogels (SIHs) with enhanced functional performance, biocompatibility, and clinical relevance.