Organ-on-a-Chip: A New Paradigm for Drug Development

Organ-on-a-Chip is a promising interdisciplinary technique emulating in vivo physiology and pathology for in vitro disease modeling, drug screening, and precision medicine. The Organ-on-a-Chip technology can be organically incorporated into the drug development pipeline from early drug discovery to preclinical screening, testing, and translation of new drugs, which bridges the gap between animal studies and clinical trials involving human subjects. The future development of personalized Organ-on-a-Chip and continuous integration of novel engineering tools (e.g., automation handling, 3D printing. and in situ multisensors) and biological concepts (e.g., patient-specific induced pluripotent stem cells and organoids) into Organ-on-a-Chip platform will unprecedentedly promote its biomedical applications. The pharmaceutical industry has been desperately searching for efficient drug discovery methods. Organ-on-a-Chip, a cutting-edge technology that can emulate the physiological environment and functionality of human organs on a chip for disease modeling and drug testing, shows great potential for revolutionizing the drug development pipeline. However, successful translation of this novel engineering platform into routine pharmacological and medical scenarios remains to be realized. In this review, we discuss how the Organ-on-a-Chip technology can have critical roles in different preclinical stages of drug development and highlight the current challenges in translation and commercialization of this technology for the pharmacological and medical end-users. Moreover, this review sheds light on the future developmental trends and need for a next-generation Organ-on-a-Chip platform to bridge the gap between animal studies and clinical trials for the pharmaceutical industry. The pharmaceutical industry has been desperately searching for efficient drug discovery methods. Organ-on-a-Chip, a cutting-edge technology that can emulate the physiological environment and functionality of human organs on a chip for disease modeling and drug testing, shows great potential for revolutionizing the drug development pipeline. However, successful translation of this novel engineering platform into routine pharmacological and medical scenarios remains to be realized. In this review, we discuss how the Organ-on-a-Chip technology can have critical roles in different preclinical stages of drug development and highlight the current challenges in translation and commercialization of this technology for the pharmacological and medical end-users. Moreover, this review sheds light on the future developmental trends and need for a next-generation Organ-on-a-Chip platform to bridge the gap between animal studies and clinical trials for the pharmaceutical industry. a biofabrication strategy that precisely prints bioinks (e.g., cells, hydrogels, and biocompatible materials) to reconstruct the structures and functions of living systems. replacement, reduction, and refinement; a guiding principle to minimize the amount of animal experimentation worldwide. describes the PK of a compound within an organism. multi-cell layer structure comprising brain endothelial cells, astrocytes, and pericytes; its selective permeability prevents drugs from nonselectively entering the brain tissue. type of multi-organ chip that recapitulates the whole human physiology within a single platform. an infectious disease caused by severe acute respiratory syndrome coronavirus 2. complex molecular network of noncellular components that provides physical support and biochemical/biophysical cues for tissue development and homeostasis. type of PSC that can be generated from somatic cells by direct introduction of four Yamanaka factors (Myc, Oct3/4, Sox2, and Klf4). an emerging research field interrogating the contribution of the hemostasis and dysfunction of mechanical properties of cells and tissues to maintain cell function, tissue development, and pathogenesis. the science and technology of manufacturing microminiaturized devices for manipulating and controlling a small volume of fluids (typically microliters to femtoliters) in a network of microchannels. type of Organ-on-a-Chip that reproduces organotypic functions of at least two types of tissues/organs to study interorgan reactions. microfluidic in vitro culture system upon which single or multiple cell types are controllably cultured within a 3D extracellular matrix to recapitulate the physiology and/or pathophysiology of in vivo tissues/organs. conceptual technology merging organoids with Organ-on-a-Chip to recapitulate the complexity of human organs by application of intrinsic tissue development process and external engineering method. quantitative relationship between drug concentrations and biochemical and physiological responses. profiles the dynamic movement of a drug in the body over time, such as the kinetics of ADME processes. manufacturing process that transfers micrometric patterns from a photomask to a light-sensitive chemical photoresist. process by which the pharmaceutical industry explores and develops new treatments or drugs. type of Organ-on-a-Chip that mainly recapitulates the structure and physiological functions of a specific tissue or organ. family of patterning techniques to reproduce structures into a soft polymer material, mostly PDMS, from a silicon mold with micro/nanoscale features.