02149nas a2200313   4500000000100000000000100001008004100002260001500043653001200058653004300070653002100113653003300134653001900167653001100186653002600197653001000223653002700233653001800260653002300278653002300301100002200324700003100346700002600377245006200403300001000465490000800475520133800483022001401821       2020                            d  c2020-10-1510aAnimals10aChemical and Drug Induced Liver Injury10adisease modeling10aDrug Evaluation, Preclinical10aDrug screening10aHumans10aLab-On-A-Chip Devices10aLiver10aLiver, Liver-on-a-Chip10amicrofluidics10aModels, Biological10aTissue engineering1 aEhsanollah Moradi1 aSasan Jalili-Firoozinezhad1 aMehran Solati-Hashjin00aMicrofluidic organ-on-a-chip models of human liver tissue  a67-830 v1163 aThe liver is the largest internal organ of the body with complex microarchitecture and function that plays critical roles in drug metabolism. Hepatotoxicity and drug-induced liver injury (DILI) caused by various drugs is the main reason for late-stage drug failures. Moreover, liver diseases are among the leading causes of death in the world, with the number of new cases arising each year. Although animal models have been used to understand human drug metabolism and toxicity before clinical trials, tridimensional microphysiological systems, such as liver-on-a-chip (Liver Chip) platforms, could better recapitulate features of human liver physiology and pathophysiology and thus, are often more predictive of human outcome. Liver Chip devices have shown promising results in mimicking in vivo condition by recapitulating the sinusoidal structure of the liver, maintaining high cell viability and cellular phenotypes, and emulating native liver functions. Here, we first review the cellular constituents and physiology of the liver and then critically discuss the state-of-the-art chip-based liver models and their applications in drug screening, disease modeling, and regenerative medicine. We finally address the pending issues of existing platforms and touch upon future directions for developing new, advanced on-chip models.  a1878-7568