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

0132692Bhatia根据这一职业奖，这位研究人员将开发一项针对阐明肝脏结构/功能关系的微型肝组织工程的综合研究计划。体内的肝脏结构将被用来定量研究和优化肝细胞与肝细胞的相互作用、肝细胞与非实质细胞的相互作用、细胞与细胞外基质的相互作用以及可溶信号的作用。微图案化表面与粘附肽RGD作为模型细胞外基质将被用来连接整合素和控制细胞与细胞之间的2D相互作用。与RGD偶联的光聚合聚乙二醇水凝胶将被用于在3D环境中将粘附肽呈现给聚集的肝细胞。含有细胞的水凝胶的光激发将被用于探索组织结构的三维特征。总而言之，这些研究将提供对整合素、钙粘附素和缝隙连接之间的相互作用以及2D和3D环境在这种相互作用中的相对作用的基本见解。所获得的见解将有助于生物人工肝反应堆和植入性结构的设计，并将对3D组织工程的实践产生重大技术影响。教育计划的重点是建立和保持妇女参与科学和工程，以及需要进一步整合工程、生物和医学领域。将扩大针对11-13岁女孩的试点外联方案，并扩大对工程行业妇女自然减员原因的研究。一本关于组织工程的跨学科本科生教科书将完成。

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.