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

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 clinic...

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Bibliographic Details
Published in:Annual review of biomedical engineering 2019-06, Vol.21 (1), p.219-239
Main Authors: Ehrlich, Avner, Duche, Daniel, Ouedraogo, Gladys, Nahmias, Yaakov
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Bioreactors
Cell Culture Techniques
Culture Media - chemistry
Culture Media - pharmacology
Drug Design
Drug Discovery
Endothelial Cells - cytology
European Union
Hepatic Stellate Cells - cytology
Hepatocytes - pathology
human on chip
Humans
in vitro models
Kupffer Cells - cytology
Lab-On-A-Chip Devices - trends
liver
Liver - metabolism
Liver - pathology
Mice
Microfluidics
microphysiological systems
organ on chip
Oxygen - chemistry
Tissue Distribution
Tissue Engineering - methods
Tissue Engineering - trends
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Summary: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.
ISSN:1523-9829
1545-4274
DOI:10.1146/annurev-bioeng-060418-052305