Date of Award

Fall 2011

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering

First Advisor

Cheul H. Cho

Second Advisor

George Collins

Third Advisor

Treena Livingston Arinzeh

Abstract

The need for a an in vitro drug screening system that mimics the structural organization of natural liver for multi-functionality and maintenance of hepatocytes has become vital in the drug development process. The objective of this study was to engineer a three-dimensional (3-D) liver model using chitosan-based nanofiber scaffolds and co-culture system (adult rat hepatocytes and 3T3-J2 fibroblasts) to mimic the natural liver and to justify its application for in vitro drug screening. Chitosan nanofiber scaffolds were fabricated by electrospinning technique. In order to promote cell adhesion on the chitosan scaffolds, the scaffolds were coated with a cell adhesion molecule, fibronectin, by adsorption. The effects of mono-culture and co-culture systems on the proliferation and functional activities of hepatocytes were investigated. Lastly, the utilization of the optimized 3-D model for drug screening was tested. The results showed that 3-D in vitro liver model in co-culture maintained hepatic morphology and shows suitable liver function such as albumin secretion for a prolonged period. The model showed acceptable cytochrome P450 enzyme activity which plays a key role in drug metabolism.

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