Dissertation Abstract

Engineering Mass Transport Improvements for Hepatic Devices: An Experimental and Computational Approach

Patients with end stage liver failure have few options that may help them prolong their lives while waiting for liver transplant surgery. To extend their wait time, one option is a bioartificial liver (BAL) device that uses viable liver cells (hepatocytes) from donor species (e.g. human or porcine) as the device's functional unit. To prevent tissue rejection between donor and recipient organelles, the hepatocyte-plasma interaction must be separated by a porous barrier membrane. Also to maintain viable and functional activity of the cells, nutrients must support their metabolic consumption requirements. Thus when designing BAL devices, it becomes obvious that mimicking the normal in-vivo capillary network is not yet a feasible approach and in-vitro alternatives for nutrient supply of 3D bioartificial devices are necessary. In particular, the transport of the nutrient O 2 through these tissues limits the scale-up of liver BAL devices.

In this work O 2 transport through gelled extra cellular matrices (ECMs) embedded within 3D BAL devices is investigated and improved. The original investigation includes tissue engineering of O 2 transport parameters and image analysis for both acellular and cellular systems. Next a computational model of O 2 flow is developed to predict O 2 transport in multiple BAL configurations. Finally, the hepatocytes are embedded into an actual BAL prototype and the cells responses to normal and improved ECM matrices are visually and functionally monitored. Through this work we developed techniques to improve O 2 transport in BAL devices which can help in the scale-up of these designs.

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