UNS: Integrated Tissue Engineering: A Gastrointestinal-Liver Platform to Investigate the Metabolism of Chemicals

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PI: Rajagopalan, Padmavathy Proposal Number: 1510920The gastrointestinal (GI) tract and the liver are organs in the body that absorb and metabolize a portion of ingested chemicals and nutrients. As such, they serve as defense mechanisms against harmful chemicals and pathogens. This project focuses on engineering an integrated GI and liver tissue to obtain information on how these organs work in unison to metabolize chemicals.The metabolism of a wide range of chemicals, drugs, and pharmaceuticals is mediated by the dual and complementary actions of the gastrointestinal (GI) tract and liver. However, there is a significant lack in understanding how integrating tissue mimics of these organs function cohesively. Current studies that use simplistic monolayers fail to capture the complex interactions in vivo. The PI proposes integrating three-dimensional (3D) tissue mimics of the liver and GI to obtain physiologically relevant information on their relative contributions to the biotransformation of chemicals. The changes in the function and properties of each tissue upon exposure to chemicals will be investigated under static and dynamic flow conditions. The following research objectives are proposed. 1. Design an integrated GI-Liver platform using a primary intestinal cell sheet and a 3D multi-cellular hepatic organotypic culture model. 2. Investigate the integrated GI-Liver platform in the presence of dynamic flow. 3. Investigate the effect of chemicals using the GI-liver platform. With regard to broader impacts, the PI will conduct K-12 educational outreach through a weeklong activity for female high school students. The students will learn to identify changes in liver and GI systems upon adding chemicals. This activity will enable students to learn how to identify and formulate a research problem, to conduct statistical analyses, and to work in teams.