Microfluidic 3D cell culture is a promising technology for the screening of drug toxicity profiles. In this study, a bioartificial liver consisting of a surface-engineered microfluidic silicon chip with microtrenches mimicking hepatic sinusoids is shown to extend 3D primary hepatocyte culture and improve in vitro drug screening for hepatotoxicity, with respect to the state-of-the-art literature on this subject. Primary hepatocytes hosted in the 3D heparin-coated microtrenches (the bioartificial liver) secrete high levels of albumin and urea over 4 weeks. The cytotoxicity of common drugs, namely, acetaminophen, chlorpromazine, and tacrine, was assessed on primary hepatocytes both at day 1 and day 7. The results suggest that mimicking hepatic sinusoids using a microtrench format allows the maintenance of difficult-to-culture primary hepatocytes to be extended to 4 weeks and provides an alternative model to animal studies for the screening of the cytotoxicity of new drugs.

Microengineered Bioartificial Liver Chip for Drug Toxicity Screening

Cozzi, Chiara;Polito, Giovanni;Barillaro, Giuseppe
;
2018-01-01

Abstract

Microfluidic 3D cell culture is a promising technology for the screening of drug toxicity profiles. In this study, a bioartificial liver consisting of a surface-engineered microfluidic silicon chip with microtrenches mimicking hepatic sinusoids is shown to extend 3D primary hepatocyte culture and improve in vitro drug screening for hepatotoxicity, with respect to the state-of-the-art literature on this subject. Primary hepatocytes hosted in the 3D heparin-coated microtrenches (the bioartificial liver) secrete high levels of albumin and urea over 4 weeks. The cytotoxicity of common drugs, namely, acetaminophen, chlorpromazine, and tacrine, was assessed on primary hepatocytes both at day 1 and day 7. The results suggest that mimicking hepatic sinusoids using a microtrench format allows the maintenance of difficult-to-culture primary hepatocytes to be extended to 4 weeks and provides an alternative model to animal studies for the screening of the cytotoxicity of new drugs.
2018
Delalat, Bahman; Cozzi, Chiara; Rasi Ghaemi, Soraya; Polito, Giovanni; Kriel, Frederik H.; Michl, Thomas Danny; Harding, Frances J.; Priest, Craig; Barillaro, Giuseppe; Voelcker, Nicolas H.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/956251
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