Smart hydrogels for tissue engineering and regenerative medicine: how far have we come

Smart hydrogels have become precision platforms that interact with complex biological cues. We formalize a 2025 definition, materials that sense a clinically relevant cue and reproducibly execute a specified, reversible function under physiologic conditions, and introduce a unified, feature-based, three-tier framework: Responsive (open-loop cue and response), Adaptive (multi-cue or stateful), and Intelligent (closed-loop sense, decide, and act). This review captures momentum from 2020 to 2025, a period marked by clinical and innovative breakthroughs, FDA-cleared formulations, and integration of advanced technologies, including AI-assisted design, fourth-dimensional (4D) bioprinting, and biohybrid interfaces. We spotlight cutting-edge developments in programmable degradation, self-healing, and multi-stimuli responsiveness, alongside emerging hydrogel fabrication strategies such as nanoparticle (NP)-laden bioinks and in situ light-activated crosslinking. Although barriers to regulation and translation remain, cross-disciplinary efforts with a sustainability- and ethics-first mind-set are redefining these materials’ capabilities. Smart hydrogels are no longer just innovative, researchers in tissue engineering and regenerative medicine are actively redefining both their clinical potential and what it means for a material to be “smart.”