Lactobionic acid-functionalized polyethersulfone hollow fiber membranes promote HepG2 attachment and function

Abstract

Surface modification of polyethersulfone hollow fibers, which are important in bio-artificial liver, is increasingly used to improve biocompatibility and promote the adhesion and proliferation of hepatocytes resulting in improved cell functionality. Hepatocytes are anchorage-dependent cells, and membrane surface modification enhances the hepatic cell adhesion and proliferation. Specific interaction of the asialoglycoprotein receptor on hepatocyte cell surfaces with a galactose moiety enhances the attachment of the cells on a biocompatible substrate. In this study, the outer surface of the polyethersulfone (P) hollow fiber membranes (HFMs) was chemically modified by covalent coupling with lactobionic acid (LBA). The energy dispersive X-ray spectrometry elemental mapping, attenuated total reflectance-Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy confirmed the LBA-coupling on the outer surface of P-LBA HFMs. Hemocompatibility study indicated the suitability of the modified membranes with human blood. These membranes showed remarkably improved biocompatibility with human primary mesenchymal stem cells and HepG2 cells. Characteristic multi-cellular spheroids of HepG2 cells were observed under scanning electron and confocal microscopy. HepG2 cell functional activity was measured by quantifying the urea synthesis, albumin secretion and glucose consumption in the culture media, which indicated the improved HepG2 functions. These experimental results clearly suggest the potentiality of these LBA-modified P HFMs as a suitable biocompatible substrate for promoting HepG2 attachment and function leading to their application in bioreactors and bio-artificial liver devices.