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.

The compatibility of hepatocytes with chemically modified porous silicon with reference to in vitro biosensors

“…4g and 4c, respectively. The observation that the hydrophilic surface leads to superior hepatocyte attachment and spreading in comparison to the hydrophobic surface is in agreement with related studies on hydrophilic glass and polymer supports [49-51]. …”

“…This improvement in cell adhesion when collagen is present, is in agreement with previous results observed on oxidized porous Si [20] and on acrylonitrile copolymers [51]. When the undecanoic acid, ozone-oxidized, and OEG-modified surfaces are exposed to collagen type I prior to cell seeding, cells adhere at levels comparable to the TCPS control (Fig.…”

“…3). However, the interplay between surface chemistry, adsorbed serum proteins, and hepatocyte protein production (particularly albumin) is not well established [49, 67] and some investigators have noted that hepatocyte protein expression can vary between hydrophilic surfaces [51]. Grant et al showed that hydrophilic, primary amine-terminated copolymer surfaces have a deleterious effect on the maintenance of primary hepatocyte function in comparison to other hydrophilic polymers.…”

Thomas Groth, PhD to serve as Co‐Editor, Europe, ESAO Representative

“…[14][15][16] Indeed, the major activities during the time of his employment at GKSS Research Center were directed to development of new polymer membranes for biohybrid liver and kidney system. This work led to the development of several membrane types that were both tissue and blood compatible based on acrylate copolymers [17][18][19][20] and a novel prototype of bioreactor for biohybrid kidney systems. 21 Further work focused on polyetherimides as new membrane materials for application in artificial organs.…”

Tissue Engineering and Organ Structure: A Vascularized Approach to Liver and Lung

“…The parenchymal and nonparenchymal components are separated to further isolate the specific cell populations (25,26). When isolated in this manner, hepatocytes exhibit in vitro degradation in function and viability because hepatocytes require cell-to-cell contact to maintain their epidermal characteristics (29,41). A novel source of tissue for hepatic tissue engineering that may avoid these limitations is the use of precision-cut liver slices.…”