Liver-on-Chip Development for Pathophysiological Emulation and Drug Toxicity Testing

Abstract

The liver is a vital organ and plays a crucial role in the homeostasis of the human body. Detoxification, metabolism, nutrient storage, hemopoiesis, and synthesis of essential biomolecules are its core functions. Hepatic enzymes are specialized in drug metabolism and biotransformation. In comparison, hepatocytes assimilate metabolites and produce several types of cytokines and proteins. Food, aging, environment, and lifestyle directly influence the liver’s health. Cancer, viral infections, alcohol abuse, and metabolic syndromes are the leading causes of hepatic pathologies. Animals and cell culture models are employed to model and investigate hepatic anomalies and therapeutics. However, genetic variation, ethical issues, and higher costs are limiting animal testing in medicine. In comparison, cell culture models exhibit poor translation capacity due to a lack of peculiar in vivo hepatic microenvironment. Therefore, this research pivots the development of a microfluidic-based in vitro liver model to overcome the ethical and translational issues. In this thesis, the focus was given to creating a liver-on-chip for modeling liver diseases and testing various pharmaceutical substances. Human hepatocytes were used to develop a liver-on-chip model, and it was monitored with embedded sensors. As a result, hepatic fibrosis modeling and anticancer drug toxicity were successfully performed, and a novel method of fibrosis developmental study was introduced. In brief, liver-on-chip is a promising model that can aid and overcome the challenges faced by clinicians and researchers in reverse engineering, translation medicine, precision medicine, and drug discovery.