Deng Jiu, Wei Wenbo, Chen Zongzheng, Lin Bingcheng, Zhao Weijie, Luo Yong, Zhang Xiuli
State Key Laboratory of Fine Chemicals, Department of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
Integrated Chinese and Western Medicine Postdoctoral research station, Jinan University,Guangzhou 510632, China.
Micromachines (Basel). 2019 Oct 7;10(10):676. doi: 10.3390/mi10100676.
Hepatology and drug development for liver diseases require in vitro liver models. Typical models include 2D planar primary hepatocytes, hepatocyte spheroids, hepatocyte organoids, and liver-on-a-chip. Liver-on-a-chip has emerged as the mainstream model for drug development because it recapitulates the liver microenvironment and has good assay robustness such as reproducibility. Liver-on-a-chip with human primary cells can potentially correlate clinical testing. Liver-on-a-chip can not only predict drug hepatotoxicity and drug metabolism, but also connect other artificial organs on the chip for a human-on-a-chip, which can reflect the overall effect of a drug. Engineering an effective liver-on-a-chip device requires knowledge of multiple disciplines including chemistry, fluidic mechanics, cell biology, electrics, and optics. This review first introduces the physiological microenvironments in the liver, especially the cell composition and its specialized roles, and then summarizes the strategies to build a liver-on-a-chip via microfluidic technologies and its biomedical applications. In addition, the latest advancements of liver-on-a-chip technologies are discussed, which serve as a basis for further liver-on-a-chip research.
肝脏病学和肝病药物研发需要体外肝脏模型。典型的模型包括二维平面原代肝细胞、肝细胞球体、肝细胞类器官和芯片肝。芯片肝已成为药物研发的主流模型，因为它能够重现肝脏微环境，并且具有良好的检测稳健性，如可重复性。含有人类原代细胞的芯片肝有可能与临床试验相关联。芯片肝不仅可以预测药物肝毒性和药物代谢，还可以连接芯片上的其他人工器官以构建芯片人，从而反映药物的整体效果。设计一个有效的芯片肝装置需要多学科知识，包括化学、流体力学、细胞生物学、电学和光学。本文综述首先介绍肝脏中的生理微环境，特别是细胞组成及其特定作用，然后总结通过微流控技术构建芯片肝的策略及其生物医学应用。此外，还讨论了芯片肝技术的最新进展，为进一步的芯片肝研究奠定基础。
