The viability and function of primary rat hepatocytes cultured on polymeric membranes developed for hybrid artificial liver devices

Abstract

Bioartificial liver devices require membranes to support the function and viability of hepatocytes because they are anchorage-dependent cells. This study investigated the ability of several polymeric membranes to support the functions of primary hepatocyte cultures. Tailor-made membranes were sought by synthesizing acrylonitrile copolymers with different comonomers resulting in ionic, hydrophilic, or reactive functional groups on the polymer surface. Hepatocyte morphology and viability were assessed by confocal microscopy, and function by the content and activities of cytochrome P450, and the expression of glutathione S-transferases. Hydrophilic membranes (polyacrylonitrile and acrylonitrile copolymerized with 2-acrylamino-2-methyl-propane sulfonic acid) were more biocompatible than hydrophobic membranes such as polysulfone. The chemistry of the hydrophilic group was important; amine groups had a deleterious effect on maintenance of the primary hepatocytes. The biocompatibility of hydrophobic membranes was improved by collagen coating. Improving the chemistry of membranes for artificial liver devices will enhance the phenotypic stability of the cells, enabling us to prolong treatment times for patients.