Manufacturing the Microstructural Niche for Liver Tissue Bioreactors

制造肝组织生物反应器的微结构利基

• 批准号: 0900254
• 负责人: Ian Nettleship
• 金额: $ 27.9万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0900254&HistoricalAwards=false
• 关键词: Manufacturing; Microstructural; Niche; Liver; Tissue

The research objective of this award is to use the structure of natural liver tissue as a guide for the processing of a new type of bioreactor that will make both liver cells and liver tissue. The microstructural niche requires that the structure of the bioreactor core mimic the essential features of the microenvironment in which stem cells reside and differentiate to form liver cells and tissue. The research approach involves dividing the microstructural niche into a series of lengthscales and then recreating these scales using a unique organ casting process in which a polymer copy of a natural liver vascular network is created and then ceramic foam is cast around it. When the ceramic is fired the vascular network of the liver is retained in the open ceramic foam that will be used to culture liver cells. The deliverables include: an understanding of the effect of the vascular structure on the processing of the ceramic foam and its consequent effect on culturing of liver cells, a test of the microstructural niche concept and engineering student education.If successful, the results of the research will provide a new generation of bioreactors that can culture cells and tissue from stem cells at physiologic densities. The liver cells and tissue manufactured in this way could be used in drug testing or transplant. Also, larger bioreactors of this type could be used to support liver function in patents that are being bridged to liver transplant. This award will also demonstrate an interdisciplinary approach that combines knowledge of cellular processes in tissue with the structure-property relationships of materials to design and manufacture bioreactors for other cells and tissue products. The educational approach will attract both undergraduate and graduate students to major in materials science and engineering by providing an example of a strong connection between materials engineering and the requirements of important biomedical devices for regenerative medicine.

该奖项的研究目标是利用天然肝组织的结构作为处理新型生物反应器的指导，该生物反应器将制造肝细胞和肝组织。 微观结构生态位要求生物反应器核心的结构模仿干细胞驻留和分化形成肝细胞和组织的微环境的基本特征。 研究方法包括将微结构生态位划分为一系列长度尺度，然后使用独特的器官铸造工艺重新创建这些尺度，在该工艺中创建天然肝脏血管网络的聚合物副本，然后在其周围铸造陶瓷泡沫。 当陶瓷被烧制时，肝脏的血管网络保留在开放的陶瓷泡沫中，用于培养肝细胞。 可交付成果包括：了解血管结构对泡沫陶瓷加工的影响及其对肝细胞培养的影响、微观结构生态位概念的测试和工程学生教育。如果成功，研究结果将提供新一代生物反应器，能够以生理密度培养干细胞的细胞和组织。 以这种方式制造的肝细胞和组织可用于药物测试或移植。此外，这种类型的较大生物反应器可用于支持与肝移植相关的专利中的肝功能。 该奖项还将展示一种跨学科方法，将组织中的细胞过程知识与材料的结构-性能关系相结合，为其他细胞和组织产品设计和制造生物反应器。 该教育方法将通过提供材料工程与再生医学重要生物医学设备要求之间紧密联系的例子，吸引本科生和研究生主修材料科学与工程。