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

职业：针对工程肝组织开发的微观结构/功能研究

• 批准号: 0538512
• 负责人: Sangeeta Bhatia
• 金额: --
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-28 至 2007-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0538512&HistoricalAwards=false
• 关键词: CAREER; Microscale; Structure; Function; Studies

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.

0132692 Bhatia在这个职业奖下，研究者将在微尺度肝组织工程中开发一个全面的研究项目，旨在阐明肝脏的结构/功能关系。 体内肝脏结构将被用作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。微图案化的表面与作为模型细胞外基质的粘附肽RGD缀合，将用于连接整合素和控制2D中的细胞与细胞的相互作用。 与RGD缀合的光聚合PEG水凝胶将用于在3D背景下将粘附肽呈递给聚集的肝细胞。 含细胞水凝胶的光图案化将用于探索组织结构的3D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相互作用以及2D和3D环境在这种相互作用中的相对作用提供基本的见解。 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，并应具有重大的技术影响的实践三维组织工程。 教育计划的重点是培养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岁女孩的试点推广方案，并将扩大对工程领域妇女流失原因的研究。 将完成一本关于组织工程的跨学科本科教科书。