Computational Modeling of 3D Printed Hepatic Spheroids Inside a Bioreactor

Abstract

Finding optimized conditions in analyzing in vitro drug hepatotoxicity especially during preliminary stages of drug development is highly appreciated. Recently, liver-on-chip platforms have been widely used in drug toxicity researches. Although perfusion in the bioreactor will enhance oxygen and nutrition delivery to the hepatocytes and decrease hypoxic zone in the bioreactor, high perfusion rate impose high shear stress on liver cells which may be detrimental or effect on their liver specific functions. Here, a three-dimensional bioreactor containing hepatic spheroids is developed numerically and velocity distribution, shear stress sensed by cells was calculated. Based on the rate of oxygen delivery and oxygen metabolic activities of the hepatocytes, the level of oxygen for each spheroid was analyzed. Also, albumin production of the hepatic cells was modeled as an example of modeling metabolic function capabilities. The computed albumin production was verified with the experimental results over 7 days of culture period which showed a good compatibility between the experimental results and numerical predictions. The results are of a great importance in finding an optimal design and working conditions of the bioreactors.