Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity

As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional (3D) in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and thus reduce in vivo animal studies and lessen drug attrition rates. The aim of this study is to establis...

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Main Authors: Wu, Lingyan, Ferracci, Gaia, Wang, Yan, Fan, Teng Fei, Cho, Nam-Joon, Chow, Pierce K. H.
Other Authors: School of Chemical and Biomedical Engineering
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/85716
http://hdl.handle.net/10220/49833
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author Wu, Lingyan
Ferracci, Gaia
Wang, Yan
Fan, Teng Fei
Cho, Nam-Joon
Chow, Pierce K. H.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Wu, Lingyan
Ferracci, Gaia
Wang, Yan
Fan, Teng Fei
Cho, Nam-Joon
Chow, Pierce K. H.
author_sort Wu, Lingyan
collection NTU
description As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional (3D) in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and thus reduce in vivo animal studies and lessen drug attrition rates. The aim of this study is to establish a functional porcine hepatocyte culture using a biofunctionalized 3D inverted colloidal crystal (ICC) hydrogel platform. The performances of non-adhesive bare poly(ethylene glycol)diacrylate (PEGDA) ICCs and PEGDA ICCs coated with either collagen type I or fibronectin have been investigated. Porcine hepatocytes viability, morphology, hepatic-specific functions and patterns of gene expression have been evaluated over a period of two weeks in culture to test diclofenac, a well-known hepatotoxic drug. Interestingly, cells in the fibronectin-functionalized scaffold exhibit different aggregation patterns and maintain better liver-specific function than those in bare ICCs and in collagen functionalized scaffold. We concluded that the 3D cell culture environment and the presence of extracellular matrix (ECM) proteins, especially fibronectin, facilitate hepatocyte viability and maintenance of the liver-specific phenotype in vitro, and enable us to predict hepatotoxicity.
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spelling ntu-10356/857162021-01-21T08:52:08Z Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity Wu, Lingyan Ferracci, Gaia Wang, Yan Fan, Teng Fei Cho, Nam-Joon Chow, Pierce K. H. School of Chemical and Biomedical Engineering School of Materials Science and Engineering Interdisciplinary Graduate School (IGS) Centre for Biomimetic Sensor Science Drug-induced Hepatotoxicity Engineering::Materials Cell Culture As drug-induced hepatotoxicity represents one of the most common causes of drug failure, three-dimensional (3D) in vitro liver platforms represent a fantastic toolbox to predict drug toxicity and thus reduce in vivo animal studies and lessen drug attrition rates. The aim of this study is to establish a functional porcine hepatocyte culture using a biofunctionalized 3D inverted colloidal crystal (ICC) hydrogel platform. The performances of non-adhesive bare poly(ethylene glycol)diacrylate (PEGDA) ICCs and PEGDA ICCs coated with either collagen type I or fibronectin have been investigated. Porcine hepatocytes viability, morphology, hepatic-specific functions and patterns of gene expression have been evaluated over a period of two weeks in culture to test diclofenac, a well-known hepatotoxic drug. Interestingly, cells in the fibronectin-functionalized scaffold exhibit different aggregation patterns and maintain better liver-specific function than those in bare ICCs and in collagen functionalized scaffold. We concluded that the 3D cell culture environment and the presence of extracellular matrix (ECM) proteins, especially fibronectin, facilitate hepatocyte viability and maintenance of the liver-specific phenotype in vitro, and enable us to predict hepatotoxicity. NRF (Natl Research Foundation, S’pore) Published version 2019-09-02T01:50:28Z 2019-12-06T16:08:57Z 2019-09-02T01:50:28Z 2019-12-06T16:08:57Z 2019 Journal Article Wu, L., Ferracci, G., Wang, Y., Fan, T. F., Cho, N.-J., & Chow, P. K. H. (2019). Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity. RSC Advances, 9(31), 17995-18007. doi:10.1039/C9RA03225H https://hdl.handle.net/10356/85716 http://hdl.handle.net/10220/49833 10.1039/C9RA03225H en RSC Advances © 2019 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. 13 p. application/pdf
spellingShingle Drug-induced Hepatotoxicity
Engineering::Materials
Cell Culture
Wu, Lingyan
Ferracci, Gaia
Wang, Yan
Fan, Teng Fei
Cho, Nam-Joon
Chow, Pierce K. H.
Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title_full Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title_fullStr Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title_full_unstemmed Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title_short Porcine hepatocytes culture on biofunctionalized 3D inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
title_sort porcine hepatocytes culture on biofunctionalized 3d inverted colloidal crystal scaffolds as an in vitro model for predicting drug hepatotoxicity
topic Drug-induced Hepatotoxicity
Engineering::Materials
Cell Culture
url https://hdl.handle.net/10356/85716
http://hdl.handle.net/10220/49833
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