Primary Liver Cells Cultured on Carbon Nanotube Substrates for Liver Tissue Engineering and Drug Discovery Applications

Abstract

Here we explore the use of two-and three-dimensional scaffolds of multi-walled-carbon nanotubes (MWNTs) for hepatocyte cell culture. Our objective is to study the use of these scaffolds in liver tissue engineering and drug discovery. In our experiments, primary rat hepatocytes, the parenchymal (main functional) cell type in the liver, were cultured on aligned nanogrooved MWNT sheets, MWNT yarns, or standard 2-dimensional culture conditions as a control. We find comparable cell viability between all three culture conditions, but enhanced production of the hepatocyte-specific marker albumin for cells cultured on MWNTs. The basal activity of two clinically relevant cytochrome P450 enzymes, CYP1A2 and CYP3A4, are similar on all substrates, but we find enhanced induction of CYP1A2 for cells on the MWNT sheets. Our data thus supports the use of these substrates for applications including tissue engineering, enhancing liver-specific functions, as well an in vitro model systems with enhanced predictive capability in drug discovery and development.

Nanomaterials as potential and versatile platform for next generation tissue engineering applications

“…Some newly developed peptide hydrogels disclosed their stimulative role in in vitro activity, with the ability to support cell attachment and stimulate the differentiation of liver progenitor cells into hepatocytes, contributing to liver tissue regeneration. Primary hepatocytes of rats cultured on MWCNTs scaffold has resulted in greater secretion of hepatocyte specific markers that suggested the applicability of these MWCNTs scaffolds in liver TE . CNTs are biocompatible, offer high mechanical strength, ease of functionalization, mechanically robust, and electrically conductive and provide a nanoscale, tunable fibrous topography to provide the structural reinforcement for tissue scaffolding.…”

“…Primary hepatocytes of rats cultured on MWCNTs scaffold has resulted in greater secretion of hepatocyte specific markers that suggested the applicability of these MWCNTs scaffolds in liver TE. 105 CNTs are biocompatible, offer high mechanical strength, ease of functionalization, mechanically robust, and electrically conductive and provide a nanoscale, tunable fibrous topography to provide the structural reinforcement for tissue scaffolding.…”

Enzymatic oxidative biodegradation of nanoparticles: Mechanisms, significance and applications

“…Moreover, particular carbonaceous materials can also cause robust changes in the functions of CYP450 system (Ji et al, 2009; Fröhlich et al, 2010; Che Abdullah et al, 2014; etc.). This catalytic responsiveness of CYP450 has lead to the development and applications of carbonaceous nanoparticles complexes with these hemoproteins as CNT-conjugated P450-biosensors (Pauwels et al, 2010; Carrara et al, 2011; Baj-Rossi et al, 2012).…”

Enhanced hepatic differentiation of human amniotic epithelial cells on polyethylene glycol-linked multiwalled carbon nanotube-coated hydrogels

“…Among which, carbon nanotubes (CNTs) exhibiting controlled nanoscale topography may represent a promising material for the creation of liver ECM mimics. Previously, compared with the cover slip control, aligned CNT sheets and CNT yarns were proven to enhance liver‐specific functions of primary rat hepatocytes, including ALB production and CYP1A2 induction (Che Abdullah et al, ). Albeit optimistic results were obtained, this study only investigated CNTs' effects to maintain rat hepatocytes.…”

“…Therefore, this study aims to examine the influence of CNTs on the hepatic differentiation of hAECs. In addition, pristine CNTs employed in an earlier study (Che Abdullah et al, 2014) were deemed to be too hydrophobic with restricted application in tissue engineering. Therefore, we applied polyethylene glycol (PEG) modification to increase CNTs' hydrophilicity for facilitating scaffold preparation, cell adherence, and growth in our design (Nayak et al, 2010;Zhao, Hu, Yu, Perea, & Haddon, 2005).…”