Multi-Stimulus-Responsive Smart Hydrogels: Response Mechanisms, Synthesis Strategies, and Frontiers in Biomedical Applications

This review systematically summarizes recent advances in multistimuli-responsive smart hydrogels, with a focus on their response mechanisms, synthesis strategies, and broad applications in the biomedical field. Based on a hydrophilic three-dimensional cross-linked network structure, smart hydrogels can sensitively respond to external stimuli such as temperature, pH, light, electricity, magnetic fields, and enzymes, enabling functions such as structural transformation, controlled drug release, and tissue repair. The article elaborates on various synthesis strategies, including chemical and physical cross-linking, microfluidics and 3D printing, double-network and nanocomposite structures, DNA-based biohydrogels, and self-healing hydrogels. It also analyzes specific response mechanisms─electrical, thermal, photoresponsive, magnetic, pH, and enzymatic─along with their application cases in drug delivery, wound healing, neural repair, and tumor therapy. Although challenges remain in functional integration and clinical translation, such as mechanical performance, biosafety, and scalable production, future developments involving multiresponse synergy, personalized design, and intelligent regulation are expected to promote their applications in precision medicine and flexible electronics.