In recent years, great emphasis has been placed on non-animal toxicological methods (e.g. in vitro models, in silico or −omics data) as alternative strategies to reduce animal-testing, in line with the 3R (Replacement, Reduction, and Refinement) principle. These methods help in the rapid and accurate estimation of preclinical efficacy and safety associated with discovery of new drugs, and reduction of failure rates in clinical trials. Currently, the in vitro studies have been in a transformation or replacement from two-dimensional (2D) cell cultures to three-dimensional (3D) cell cultures that can mimic the physiology of tissues, organs, and organisms.
In this context, organ-on-a-chip systems have been developed by integration of 3D culture models with emerging microfluidic technologies. Since the organ-on-a-chip systems provide a good understanding of dose-response and toxicity mechanisms in drug research and development (R&D), the impact of xenobiotics on the human body can be predicted in a satisfactory level. Besides, these systems may support assessment of pharmacokinetic-pharmacodynamic parameters as well as detection of drug resistance. Models can be generated as “disease-models-on-a-chip” or with healthy cells to the evaluate response to xenobiotic under test.
In this review, we will focus on the microfluidic systems being used in organ-on-a-chip systems and emphasize their potential for toxicity studies in which micro-environments of examples including liver, kidney, brain, lung, heart, and intestines and their physiological properties as reflected to organ-on-a-chip models.