(447b) A Liver on a Chip Model Mimicking the Intrahepatic Bile Duct

Every year millions of people in U.S and around the world suffer from acute or chronic liver injuries. The cost for treatment and care of patients in U.S can rise to $10 billion per year. Furthermore, for those patients that require liver transplantation, there is always a shortage due to lower number of donors compared to recipients. One way to enhance the functionality of the engineered tissues is to design and generate structures that mimic the intricate architecture and complexity of native organs and tissues. Mimicking the bile duct structure for liver tissue engineering applications is of great importance. Currently, there is a lack of model to study the bile duct behavior in-vitro for drug toxicity tests that can be used for simulating bile duct disease such as cholangiocarcinoma and biliary atresia. Cholangiocytes are the epithelial cells of the bile duct which their main function is to modify the bile secreted by the hepatocytes. Intrahepatic bile duct are small ducts inside the liver which contain cholangiocytes. Hollow fibers are a unique solution to mimic the biliary tree since they provide wide area of cell adhesion and better nutrient and oxygen transfer to the cells. One of the goals of liver tissue engineering is to fabricate tubular fibers to replace the affected bile duct. These bile ducts in-vivo are surrounded by hepatocyte. In this research a liver-on-chip model was built to mimic the intrahepatic bile ducts by using hollow fibers internally seeded with cholangiocytes and microcapsules containing hepatocytes. First, hepatocytes were encapsulated in glycosaminoglycans (GAG)-chitosan microcapsules using electrospraying method. These microcapsules along with the hollow fibers seeded with cholangiocytes were transferred to the chip model which has an input and an output. It is believed that the presence of non-parenchymal cells in the in-vitro liver models will accelerate hepatocyte metabolic activity. To test the designed system, the output of the chip was testes for albumin and urea production and the results were compared with a chip model containing only hepatocytes. In addition, to see if the system can mimic the intrahepatic bile duct function, concentration of bile acids was calculated at different time intervals throughout the experiment. This in-vitro intrahepatic model is one of the first models mimicking the in-vivo conditions of the intrahepatic bile duct which can be used for different applications from drug toxicity test to study of liver disease.