CAREER: Microscale Structure/Function Studies Towards Development of Engineered Liver Tissue

[01:26 . 92] batia研究员将在微尺度肝组织工程领域开展全面的研究项目，旨在阐明肝脏的结构/功能关系。体内肝脏结构将作为定量研究和优化肝细胞与肝细胞相互作用、肝细胞与非实质细胞相互作用、细胞与细胞外基质相互作用以及可溶性线索作用的指南。与粘附肽RGD结合的微图案表面作为模型细胞外基质将用于连接整合素和控制二维细胞间相互作用。与RGD结合的光聚合PEG水凝胶将用于在3D环境中呈现粘附肽聚集的肝细胞。含细胞水凝胶的光模式将用于探索组织结构的三维特征。总的来说，这些研究将为整合素、钙粘蛋白和间隙连接之间的串扰以及二维和三维环境在这种串扰中的相对作用提供基本的见解。所获得的见解将有利于生物人工肝反应器和植入式结构的设计，并将对3D组织工程的实践产生重大的技术影响。教育计划的重点是建立和保持妇女对科学和工程的参与，以及在工程、生物学和医学领域进一步整合的必要性。将扩大针对11-13岁女孩的试点外展方案，并将扩大对工程领域妇女流失原因的研究。完成一本跨学科的组织工程本科教材。

0132692BhatiaUnder this CAREER Award, the investigator will develop a comprehensive research program in Microscale Hepatic Tissue Engineering oriented towards elucidating the structure/function relationship of the liver. The liver architecture in vivo will be used as a guide to quantitatively investigate and optimize hepatocyte-to-hepatocycte cell interactions, hepatocycte-to-non-parenchymal cell interactions, cell-to-extracellular matrix interactions, and the role of soluble cues. Micropatterned surfaces conjugated with the adhesive peptide RGD as a model extracellular matrix will be used to ligate integrins and control cell-to-cell interactions in 2D. Photopolymerized PEG hydrogels conjugated with RGD will be used to present an adhesive peptide to aggregated hepatocytes in a 3D context. Photopatterning of cell-containing hydrogels will be used to explore 3D features of tissue structure. Collectively, the studies will provide fundamental insight into the cross-talk between integrins, cadherins, and gap junctions as well as the relative role of 2D and 3D environments in this cross-talk. Insights gained will benefit design of bioartificial liver reactors and implantable constructs and should have a major technological impact on the practice of 3D tissue engineering. The educational plan focused on building and maintaining the involvement of women in science and engineering and the need for further integration across the fields of engineering, biology, and medicine. A pilot outreach program for 11-13 year old girls would be expanded and a study of reasons for attrition of women in engineering would be broadened. An interdisciplinary undergraduate textbook on Tissue Engineering would be completed.