Advances in organ-on-a-chip engineering

Predicting the effects of drugs before human clinical trials is at the heart of drug screening and discovery processes. The cost of drug discovery is steadily increasing owing to the limited predictability of 2D cell culture and animal models. The convergence of microfabrication and tissue engineering gave rise to organ-on-a-chip technologies, which offer an alternative to conventional preclinical models for drug screening. Organ-on-a-chip devices can replicate key aspects of human physiology crucial for the understanding of drug effects, improving preclinical safety and efficacy testing. In this Review, we discuss how organ-on-a-chip technologies can recreate functions of organs, focusing on tissue barrier properties, parenchymal tissue function and multi-organ interactions, which are three key aspects of human physiology. Specific organ-on-a-chip systems are examined in terms of cell sources, functional hallmarks and available disease models. Finally, we highlight the challenges that need to be overcome for the clinical translation of organ-on-a-chip devices regarding materials, cellular fidelity, multiplexing, sensing, scalability and validation. Organ-on-a-chip devices can recreate key aspects of human physiology in vitro, offering an alternative to animal models for preclinical drug testing. This Review examines how tissue barrier properties, parenchymal tissue function and multi-organ interactions can be recreated in organ-on-a-chip systems and applied for drug screening.