Microphysiological Systems: Design, Fabrication, and Applications

Microphysiological systems, including organoids, 3-D printed tissue constructs, and organ-on-a-chip systems (organ chips), are physiologically relevant in vitro models and have experienced explosive growth in the past decades. Different from conventional, tissue culture, plastic-based in vitro models or animal models, microphysiological systems recapitulate key microenvironmental characteristics of human organs and mimic their primary functions. The advent of microphysiological systems is attributed to evolving biomaterials, micro/nanotechnologies, and stem cell biology, which enable precise control over the matrix properties and the interactions between cells, tissues, and organs in physiological conditions. As such, microphysiological systems have been developed to model a broad spectrum of organs from microvasculature and eyes to lungs and many others to understand human organ development and disease pathology and facilitate drug discovery. Multiorgans-on-a-chip systems have also been developed by integrating multiple associated organ chips in a single platform, which allow study and employment of the organ function from a systematic approach. Here we first discuss the design principles of microphysiological systems with a focus on the anatomy and physiology of organs and, then, review the commonly used fabrication techniques and biomaterials for microphysiological systems. Subsequently, we discuss recent developments in microphysiological systems and provide our perspectives on advancing microphysiological systems for preclinical investigation and drug discovery of human disease.