Microphysiological systems as reliable drug discovery and evaluation tools: Evolution from innovation to maturity

Microphysiological systems (MPSs), also known as organ-on-chip or disease-on-chip, have recently emerged to reconstitute the in vivo cellular microenvironment of various organs and diseases on in vitro platforms. These microfluidics-based platforms are developed to provide reliable drug discovery and regulatory evaluation testbeds. Despite recent emergences and advances of various MPS platforms, their adoption of drug discovery and evaluation processes still lags. This delay is mainly due to a lack of rigorous standards with reproducibility and reliability, and practical difficulties to be adopted in pharmaceutical research and industry settings. This review discusses the current and potential use of MPS platforms in drug discovery processes while considering the context of several key steps during drug discovery processes, including target identification and validation, preclinical evaluation, and clinical trials. Opportunities and challenges are also discussed for the broader dissemination and adoption of MPSs in various drug discovery and regulatory evaluation steps. Addressing these challenges will transform long and expensive drug discovery and evaluation processes into more efficient discovery, screening, and approval of innovative drugs.