Tissue Engineering Resource Center: TR&D2

SUMMARY TR&D2 will continue to focus on the development of imaging enabled micro-scale bioreactors with optical control and sensing and spatiotemporal visualization of biological events. These systems, containing one or more tissues, are often called “organs-on-chip” because of their ability to recapitulate organ level functions, such as liver metabolism or contractile function of the heart. Because of this ability to model human physiology and disease, they overcome many of the limitations of current cell and animal models and are being considered a fast-track opportunity for tissue engineering to advance drug development and precision medicine. In current TERC, we have developed bioreactors with optical control and sensing and spatiotemporal visualization of biological events, such as optogenetic control of cell differentiation to engineer stratified tissues. We also established ability to maintain each tissue in its optimal niche while linking them to each other by vascular flow to allow cross-talk. TERC renewal will leverage these advances to develop a cohesive approach to the design of deployable imaging-enabled micro-scale bioreactors for broad use. As in current TERC, all tissues will be derived from iPSCs, to allow patient specific and precision medicine studies. To advance biological fidelity of these human tissue models, we will incorporate a bone marrow module to provide sustained supply of immune cells, which play major roles in many diseases. In Aim 1, we will establish a configurable plug-and-play platform with several different modalities for real-time imaging and feedback control, as a foundational technology for studying human pathophysiology, in the context of both individual organ studies (TR&D2 Aim 2 and Aim 3) and systemic conditions (TR&D3 Aim 2). To demonstrate broad utility for studies of disease, injury and regeneration, we will address two major challenges in the field: generation of electromechanically active tissues (Aim 2: cardiac -bone marrow bioreactor) and appropriate zoning and responses to physiologic loads (Aim 3: synovial joint – bone marrow bioreactor).