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

PI：Rajagopalan，Padmavathy建议编号：1510920胃肠道(GI)和肝脏是人体内吸收和代谢部分摄入的化学物质和营养的器官。因此，它们可以作为防御有害化学物质和病原体的机制。这个项目的重点是设计一个整合的GI和肝脏组织，以获得这些器官如何协调代谢化学物质的信息。一系列化学品、药物和药物的代谢是由胃肠道(GI)和肝脏的双重和互补作用调节的。然而，对于整合这些器官的组织模拟如何发挥凝聚力还缺乏了解。目前使用简单单分子膜的研究未能捕捉到体内复杂的相互作用。PI建议整合肝脏和GI的三维(3D)组织模拟，以获得关于它们对化学物质生物转化的相对贡献的生理相关信息。在静态和动态流动条件下，将研究暴露在化学品中的每个组织的功能和特性的变化。提出了以下研究目标。1.利用原代肠道细胞片和三维多细胞肝脏器官型培养模型设计了一个一体化的GI-肝脏平台。2.研究了动态流动条件下的一体化GI-Liver平台。3.使用GI-Liver平台研究化学物质的影响。至于更广泛的影响，PI将通过为期一周的女高中生活动，开展K-12教育推广活动。学生们将学习在添加化学物质后识别肝脏和胃肠道系统的变化。这项活动将使学生学习如何识别和形成研究问题，进行统计分析，并进行团队合作。

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.