Recent advances in liver-on-chips: Design, fabrication, and applications.

The liver is a multifunctional organ and the metabolic center of the human body. Most drugs and toxins are metabolized in the liver, resulting in varying degrees of hepatotoxicity. The damage of liver will seriously affect human health, so it is very important to study the prevention and treatment of liver diseases. At present, there are many research studies in this field. However, most of them are based on animal models, which are limited by the time-consuming processes and species difference between human and animals. In recent years, liver-on-chips have emerged and developed rapidly and are expected to replace animal models. Liver-on-chips refer to the use of a small number of liver cells on the chips to simulate the liver microenvironment and ultrastructure in vivo. They hold extensive applications in multiple fields by reproducing the unique physiological functions of the liver in vitro. In this review, we first introduced the physiology and pathology of liver and then described the cell system of liver-on-chips, the chip-based liver models, and the applications of liver-on-chips in liver transplantation, drug screening, and metabolic evaluation. Finally, we discussed the currently encountered challenges and future trends in liver-on-chips.