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Annu Rev Biomed Eng. 2019 Jun 4;21:219-239. doi: 10.1146/annurev-bioeng-060418-052305.

Challenges and Opportunities in the Design of Liver-on-Chip Microdevices.

Author information

1
Grass Center for Bioengineering, Benin School of Computer Science and Engineering, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
2
L'Oréal Research and Innovation, Aulnay-sous-Bois 93600, France.
3
Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
4
Tissue Dynamics Ltd., Jerusalem 91904, Israel.

Abstract

The liver is the central hub of xenobiotic metabolism and consequently the organ most prone to cosmetic- and drug-induced toxicity. Failure to detect liver toxicity or to assess compound clearance during product development is a major cause of postmarketing product withdrawal, with disastrous clinical and financial consequences. While small animals are still the preferred model in drug development, the recent ban on animal use in the European Union created a pressing need to develop precise and efficient tools to detect human liver toxicity during cosmetic development. This article includes a brief review of liver development, organization, and function and focuses on the state of the art of long-term cell culture, including hepatocyte cell sources, heterotypic cell-cell interactions, oxygen demands, and culture medium formulation. Finally, the article reviews emerging liver-on-chip devices and discusses the advantages and pitfalls of individual designs. The goal of this review is to provide a framework to design liver-on-chip devices and criteria with which to evaluate this emerging technology.

KEYWORDS:

human on chip; in vitro models; liver; microphysiological systems; organ on chip

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