SUMMARY Tissue engineering is rapidly developing, but remains limited by (i) scaffold and bioreactor designs that are based on predetermined parameters, and (ii) the lack of real-time, nondestructive measurements of cell and tissue function. To overcome these two limitations, we will develop adaptive-responsive biomaterials that can sense environmental signals and actuate the cells, and imaging-enabled bioreactors with real-time spatiotemporal control of engineered tissues with feedback from the measured cell responses. Our goal is to offer these advances to the tissue engineering community and translate them into clinics. The proposed renewal of the Tissue Engineering Resource Center (TERC) brings together a highly productive interdisciplinary team of actively collaborating investigators from Columbia University (lead institution), Tufts University, Columbia University Irving Medical Center and Stevens Institute of Technology. An Administrative Board will coordinate the Center’s activities, with the oversight and guidance of an exceptionally strong External Advisory Committee, formed from the world leaders in tissue engineering and clinical translation. TERC will partner with a number of existing resources (please see 18 letters of support), and will benefit from the exceptional resources provided by our institutions and the very generous financial support of the Columbia University School of Engineering ($2,125,000 over the five-year cycle). The technical components of the Center are three Technology Research and Development Projects (TR&D1: Adaptive-responsive biomaterials; TR&D2: Imaging enabled bioreactors; TR&D3: Translational technologies), 17 Collaborative Projects, and 16 Service Projects. We also propose a robust and highly diverse Technology, Training, and Dissemination program for biomedical investigators to facilitate the use of new technologies and raise awareness about TERC, and comprehensive Outreach to students, the general public, underrepresented and underserved communities. With a highly innovative scientific premise, extensive foundational research, strong leadership and institutional support, experience in translational research, and long history of collaboration among the lead investigators, we are confident that the Center will accomplish its mission of serving as a transformative driving force in the field of tissue engineering.