A 3-D Biomimetic Liver for Predicting Physiology and Toxicity

The liver plays a central role in human drug interactions and is also the most common target for drug-induced toxicity, resulting in costly, late stage drug failures. In this project, we derive inspiration from the building blocks of the liver, the liver sinusoid and the acinus structure, to build a realistic microfluidic liver platform to accelerate drug testing and toxicology studies. The design consists of a microfabricated platform with parallel cords (microfabricated grooves) separated by thin walls. These cords house a three dimensional analog of the liver sinusoid populated with human liver cells. Using a step-by-step approach, we introduce primary hepatocytes into these cords, followed by the non-parenchymal cells (NPCs), including endothelial cells, stellate cells and Kuppfer cells. These NPCs not only support optimal hepatocyte function but also directly contribute to drug metabolism and induced toxicological challenges. Using strategies to mimic in vivo flow characteristics, including nutrient and oxygen zonation, we aim to deliver a platform that closely mimics the in vivo liver and therefore produces data with improved predictive capabilities.