Fig. 3

Engineered liver devices. a Bioartificial liver. Engineered liver devices are at different scales and have a wide range of applications. The Bioartificial Liver (BAL) is a bioreactor system which bears hepatocytes in a variety of formats (hollow fiber vs. spheroid vs. monolayer culture). A large number of hepatocytes, approximately 10% of the adult liver, are needed to provide appropriate level of functions. Typically, the BAL is used for acute liver disease. In this case, it can be used a bridge to transplant, or as a way to regenerate acutely injured liver. The main challenges and applications are as shown. b Machine Perfusion. This is a technique used for several applications in animal models. The whole liver is connected to the perfusion device and perfusate is oxygenated and pumped to perfuse the whole liver under hypothermic or normothermic conditions. The technique is used to preserve organs after harvest, as opposed to storage of organs without flow in organ preservation solution. Machine perfusion is also used to condition marginal livers, for example by adding medium components to reverse fatty liver disease in a donor liver. Finally, machine perfusion can be used to understand complex, whole liver metabolic functions by measuring metabolites at inlet and outlet of the device under various experimental conditions. The main challenges and applications are as shown. c Hepatocyte Microdevices. This is a technique in which the hepatocytes are placed within miniature microfabricated devices so that they display physiological functions. Both animal and human liver on a chip applications are possible, and are valuable for assessing hepatotoxicity, drug metabolism, and pharmacokinetics, in the setting of drug discovery. These devices can potentially replace animals in the drug discovery pipeline. Patient-specific hepatocytes can be used to understand how genetic variations effect drug metabolism. Multiple cell types can be used in a circuit to better model the human body. The main challenges and applications are as shown