Emerging Smart and Adaptive Hydrogels for Next-Generation Tissue Engineering

Tissue engineering is entering a new era, one defined not by passive scaffolds but by smart, adaptive biomaterials that can sense, think, and respond to their surroundings. These next-generation materials go beyond simply providing structure; they interact with cells and tissues in real time. Recent advances in mechanically responsive hydrogels and dynamic crosslinking have demonstrated how materials can adjust their stiffness, repair themselves, and transmit mechanical cues that directly influence cell behavior and tissue growth. Meanwhile, in vivo studies are demonstrating how engineered materials can harness the body’s own mechanical forces to activate natural repair programs without relying on growth factors or additional ligands, paving the way for minimally invasive, force-based therapies. The emergence of electroactive and conductive biomaterials has further expanded these capabilities, enabling two-way electrical communication with excitable tissues such as the heart and nerves, supporting more coordinated and mature tissue growth. Meanwhile, programmable bioinks and advanced bioprinting technologies now allow for precise spatial patterning of multiple materials and living cells. These printed constructs can adapt and regenerate after implantation, combining architectural stability with flexibility to respond to biological changes. This review brings together these cross-cutting advances, dynamic chemical design, mechanobiology-guided engineering, bioelectronic integration, and precision bio-fabrication to provide a comprehensive view of the path forward in this field. We discuss key challenges, including scalability, safety compliance, and real-time sensing validation, alongside emerging opportunities such as in situ stimulation, personalized electromechanical sites, and closed loop “living” implants. Taken together, these adaptive biomaterials represent a transformative step toward information-rich, self-aware scaffolds capable of guiding regeneration in patient-specific pathways, blurring the boundary between living tissue and engineered material.