The development of Human Organs-on-Chips (Organ Chips) - microfluidic culture devices lined by living human tissues that recapitulate organ-level pathophysiology and offer a new approach to replace animal testing in drug development and advance personalized medicine - is often viewed through the lens of bioengineering and microfabrication. However, the origin of this technology lies deeply rooted in pursuit of a fundamental understanding of cellular biophysics and human mechanobiology. This review is written primarily from a personal perspective, and it traces work beginning 50 years ago, which describes how the need for new experimental tools to test a novel tensegrity model of cellular mechanics and mechanotransduction led to the melding of cell biology, engineering, and computer microchip manufacturing approaches, and eventually to the birth of Organ Chip technology. The initial driving force was the need to artificially control the shape of living cells to demonstrate the central role that mechanical forces play in biological control. This led to the adoption of soft lithography to create tailored cell culture environments and later to the development of mechanically active, microfluidic Organ Chip culture systems. By recapitulating tissue-tissue interfaces and the dynamic mechanical microenvironments of living organs, Organ Chips enable understanding of mechanobiological phenomena that are unattainable with traditional static cell cultures or animal models. This path of research has confirmed the indispensable importance of physical forces for physiological control, in addition to accelerating drug discovery, enhancing toxicity assessment, and deepening our comprehension of disease pathogenesis.
D E Ingber (Thu,) studied this question.