The native liver as inspiration to create superior in vitro hepatic models

Drug induced liver injury (DILI) is one of the major reasons of drug withdrawal during the different phases of drug development. The later in the drug development a drug is discovered to be toxic, the higher the economical as well as the ethical impact will be. In vitro models for early detection of drug liver toxicity are under constant development, however to date a superior model of the liver is still lacking. Ideally, a highly reliable model should be established to maintain the different hepatic cell functionalities to the greatest extent possible, during a period of time long enough to allow for tracking of the toxicity of compounds. In the case of DILI, toxicity can appear even after months of exposure. To reach this goal, an in vitro model should be developed that mimics the in vivo liver environment, function and response to external stimuli. The different approaches for the development of liver models currently used in the field of tissue engineering will be described in this review. Combining different technologies, leading to optimal materials, cells and 3D-constructs will ultimately lead to an ideal superior model that fully recapitulates the liver.