Manufacturing the Microstructural Niche for Liver Tissue Bioreactors

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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.