Organ‐on‐chip models: Implications in drug discovery and clinical applications

• Published in: Journal of cellular physiology Vol. 234; no. 6; pp. 8352 - 8380
• Main Authors: Mittal, Rahul, Woo, Frank W., Castro, Carlo S., Cohen, Madeline A., Karanxha, Joana, Mittal, Jeenu, Chhibber, Tanya, Jhaveri, Vasanti M.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-06-2019
• Subjects: Animal models; Biochips; Bioengineering; bioprinting; Bioprinting - methods; Brain; Clinical trials; Drug Development; drug discovery; Drug Evaluation, Preclinical; Failure rates; Gastrointestinal system; Gastrointestinal tract; Heart; Humans; Intestine; Kidneys; Lab-On-A-Chip Devices; Lead - adverse effects; Lead - therapeutic use; Lead compounds; Liver; Lungs; Medical research; microfabrication; Microtechnology - methods; New technology; Organ Culture Techniques; organoid; Organoids; Organoids - drug effects; Organoids - growth & development; Organs; organ‐on‐chip model; Pathogenesis; Pharmacodynamics; Pharmacokinetics; Pharmacology; Placenta; Precision medicine; Retina; Stomach; Therapeutic applications; Three dimensional models; Three dimensional printing; Two dimensional models; microfabrication; drug discovery; bioprinting; organ-on-chip model; organoid
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27729

Before a lead compound goes through a clinical trial, preclinical studies utilize two‐dimensional (2D) in vitro models and animal models to study the pharmacodynamics and pharmacokinetics of that lead compound. However, these current preclinical studies may not accurately represent the efficacy and safety of a lead compound in humans, as there has been a high failure rate of drugs that enter clinical trials. All of these failures and the associated costs demonstrate a need for more representative models of human organ systems for screening in the preclinical phase of drug development. In this study, we review the recent advances in in vitro modeling including three‐dimensional (3D) organoids, 3D microfabrication, and 3D bioprinting for various organs including the heart, kidney, lung, gastrointestinal tract (intestine–gut–stomach), liver, placenta, adipose, retina, bone, and brain as well as multiorgan models. The availability of organ‐on‐chip models provides a wealth of opportunities to understand the pathogenesis of human diseases and provide a potentially better model to screen a drug, as these models utilize a dynamic 3D environment similar to the human body. Although there are limitations of organ‐on‐chip models, the emergence of new technologies have refined their capability for translational research as well as precision medicine.
A schematic comparison of two‐dimensional and three‐dimensional cell culture.