Computational Fluid Dynamics Investigation of the Effect of the Fluid-Induced Shear Stress on Hepatocyte Sandwich Perfusion Culture

Abstract

Primary hepatocyte in vitro culture is a challenging area in liver tissue engineering. Hepatocyte viability and functions drop significantly after isolation step. The perfusion culture is a promising culture method to maintain cell viability and function in vitro for long term. Hepatocytes cultured in perfusion condition have better oxygen and nutrient supply due to improved mass transfer. The metabolite wastes excreted by cells can also be removed effectively in the perfused flow, avoiding local accumulation of these wastes which deteriorates cell functions. However, hepatocytes are sensitive to shear stress associated with the flow rate in perfusion culture and are shielded by sinusoidal endothelial cells in the liver to avoid direct exposure to shear stress. Fluid-induced high shear stress in perfusion culture may cause detrimental effect on hepatocyte viability and functions. In the current study, we simulated the profile of fluid-induced shear stress under different flow rate in our sandwich perfusion bioreactor using computation fluid dynamics (CFD) method, and investigated the effect of shear stress on the cell function. The results indicated that hepatocyte function can be maintained in long term under moderate shear stress in perfusion culture.