Manufacturing the Microstructural Niche for Liver Tissue Bioreactors

该奖项的研究目标是利用天然肝组织的结构作为指导，用于处理一种新型的生物反应器，该生物反应器将同时制造肝细胞和肝组织。 微结构生态位要求生物反应器核心的结构模拟干细胞驻留并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龛分成一系列长度尺度，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，该陶瓷泡沫将用于培养肝细胞。 可交付成果包括：了解血管结构对陶瓷泡沫加工的影响及其对肝细胞培养的影响，测试微结构生态位概念和工程专业学生教育。如果成功，研究结果将提供新一代生物反应器，可以在生理密度下从干细胞培养细胞和组织。 以这种方式制造的肝细胞和组织可以用于药物测试或移植。此外，这种类型的更大的生物反应器可以用于支持正在桥接到肝移植的患者的肝功能。 该奖项还将展示一种跨学科的方法，将组织中细胞过程的知识与材料的结构-性质关系相结合，以设计和制造用于其他细胞和组织产品的生物反应器。 教育方法将吸引本科生和研究生主修材料科学与工程，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。

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.