Extracellular matrix-inspired 4D SMART biomaterials for bioprinting in tissue engineering

Tissue development and regeneration arise from a dynamic interplay among cells, the extracellular matrix (ECM), and surrounding biophysical and biochemical cues. These interactions form the basis for stimuli-responsive materials for advanced regenerative technologies (SMART) that drive innovation in 4D bioprinting for tissue engineering. This review discusses the biophysical foundations of SMART materials, emphasizing native ECM components, their interactions, and organ-specific properties that inform biomimetic material design. We highlight recent advances in 4D SMART systems, including ionic self-healing, pH-, thermal-, hydration-, and magneto-responsive materials, and their roles in mimicking developmental and regenerative processes. Followed by a comparative overview of these stimuli-responsive material classes—benchmarked against each other, native ECM performance, and clinical translation requirements—revealing persistent gaps in long-term stability, multi-stimuli integration, and regulatory feasibility. Together, these insights outline an interdisciplinary framework for designing adaptive, responsive biomaterials that guide tissue morphogenesis and advance the future of regenerative medicine.