Design and engineering of organ-on-a-chip.

Organ-on-a-chip (OOC) is an emerging interdisciplinary technology that reconstitutes the structure, function, and physiology of human tissues as an alternative to conventional preclinical models for drug screening. Over the last decade, substantial progress has been made in mimicking tissue- and organ-level functions on chips through technical advances in biomaterials, stem cell engineering, microengineering, and microfluidic technologies. Structural and engineering constituents, as well as biological components, are critical factors to be considered to reconstitute the tissue function and microenvironment on chips. In this review, we highlight critical engineering technologies for reconstructing the tissue microarchitecture and dynamic spatiotemporal microenvironment in OOCs. We review the technological advances in the field of OOCs for a range of applications, including systemic analysis tools that can be integrated with OOCs, multiorgan-on-chips, and large-scale manufacturing. We then discuss the challenges and future directions for the development of advanced end-user-friendly OOC systems for a wide range of applications.