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.

中文翻译：

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肝片微器件设计中的挑战和机遇。

肝脏是异源生物代谢的中心枢纽，因此是最容易受到化妆品和药物诱导的毒性的器官。在产品开发过程中未能检测到肝毒性或评估化合物清除率是上市后产品撤回的主要原因，对临床和财务造成了灾难性的后果。尽管小动物仍然是药物开发中的首选模型，但欧盟最近禁止使用动物，这迫切需要开发精确有效的工具来检测化妆品开发过程中的人肝毒性。本文简要介绍了肝脏的发育，组织和功能，并着重介绍了长期细胞培养的技术水平，包括肝细胞来源，异型细胞间相互作用，需氧量和培养基配方。最后，本文回顾了新兴的片上肝脏设备，并讨论了单个设计的优点和不足。这篇综述的目的是提供一个框架，以设计用于评估该新兴技术的片上肝脏设备和标准。