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，加工一种新型生物反应器，既能制造肝细胞，也能制造肝组织。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。研究方法包括将微观结构龛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，其中创建天然肝脏血管网络的聚合物副本，然后在其周围浇筑陶瓷泡沫。当陶瓷烧制时，肝脏的血管网保留在开放的陶瓷泡沫中，将用于培养肝细胞。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，对微观结构生态位概念和工程学生教育的测试。如果成功，研究结果将提供新一代生物反应器，可以在生理密度下培养干细胞的细胞和组织。用这种方法制造的肝细胞和组织可用于药物试验或移植。此外，这种类型的大型生物反应器可以用于支持肝脏功能的专利，正在与肝脏移植相结合。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-性质关系结合起来，设计和制造用于其他细胞和组织产品的生物反应器。通过提供材料工程与再生医学重要生物医学设备需求之间紧密联系的例子，该教育方法将吸引本科生和研究生主修材料科学与工程。

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.