Drug-induced liver injury (DILI) remains the most common cause for acute liver failure in the world and is a leading cause of compound attrition in drug discovery. Although sufficient at capturing most intrinsic events, current models used in drug discovery have limitations as they are not effective at predicting or understanding more complex DILI events in humans. Furthermore, for testing new human-specific modalities, cell lines/animal models are less suitable due to genetic or immunological response differences. Using the PhysioMimix® Organ-on-a-Chip (OOC) System, human and preclinical animal microphysiological system (MPS) models have been developed to bridge these gaps.

The PhysioMimix Multi-chip Liver-12 plate contains 12 individually perfused chips for MPS culture. Due to the relatively large size of each liver microtissue and high volume of media from which to sample, the approach enables toxicity pathways to be characterized, deliveringmechanistic insights that better inform preclinical safety studies. Primary human and animal liver cells (hepatocytes and Kupffer cells) were cultured as 3D microtissues on scaffolds under perfusion for two weeks in Liver-12 plates and assessed for their ability to predict preclinical and clinical safety outcomes.