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

Abstract

Aim: Bioartificial liver devices require membranes to support the function and viability of hepatocytes as they are anchorage-dependent cells. This study investigates the ability of several polymeric membranes to support the functions of primary hepatocyte cultures. Methods: Tailor-made membranes were sought by (i) synthesising acrylonitrile copolymers with different comonomers resulting in ionic, hydrophilic or reactive functional groups on the polymer surface and (ii) modifying the surface of polysulfone membranes. Hepatocyte morphology and viability was assessed by confocal microscopy, and function by the content and activities of cytochrome P450, and the expression of glutathione-S-transferases. Results: A polyacrylonitrile membrane containing acrylamido-2-methyl-propansulfonic acid as comonomer was found to be the most compatible option for maintaining hepatocyte morphology and function. It maintained viable, functional cells for at least 16 days in culture, and collagen coating improved its performance for the first 7 days. Conclusion: 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.