3D Hepatic In Vitro Models as Tools for Toxicity Studies

Various hepatic models are currently used as in vitro models alternative to in vivo animal studies for toxicity assessment. Most of these models including the in vivo animal models are limited in the accurate prediction of toxicity. Major reasons are inadequate in vitro culture techniques and in case of in vivo animal models, the species specific differences in the metabolism of xenobiotics. Conventional 2D hepatocyte cultures rapidly lose liver-like functionality leading to high discrepancies between experimental in vitro data and actual in vivo situation. In contrast, 3D liver cell cultures mimic the in vivo tissue and show improved organotypic functionality allowing realistic assessment of drug metabolism, and adverse/toxic effects. Such 3D engineered models, by ensuring prolonged viability and functionality, can also be applied for repeated dose testing in chronic toxicity studies. In this review, we focus on recent advances in the development and characterization of three-dimensional in vitro liver models. We discuss different 3D systems from small-scale bioreactors and spheroids to micro-structured devices and highlight their application in toxicological studies.