From organ-on-chip to body-on-chip: The next generation of microfluidics platforms for in vitro drug efficacy and toxicity testing.

The high failure rate in drug development is often attributed to the lack of accurate pre-clinical models that may lead to false discoveries and inconclusive data when the compounds are eventually tested in clinical phase. With the evolution of cell culture technologies, drug testing systems have widely improved, and today, with the emergence of microfluidics devices, drug screening seems to be at the dawn of an important revolution. An organ-on-chip allows the culture of living cells in continuously perfused microchambers to reproduce physiological functions of a particular tissue or organ. The advantages of such systems are not only their ability to recapitulate the complex biochemical interactions between different human cell types but also to incorporate physical forces, including shear stress and mechanical stretching or compression. To improve this model, and to reproduce the absorption, distribution, metabolism, and elimination process of an exogenous compound, organ-on-chips can even be linked fluidically to mimic physiological interactions between different organs, leading to the development of body-on-chips. Although these technologies are still at a young age and need to address a certain number of limitations, they already demonstrated their relevance to study the effect of drugs or toxins on organs, displaying a similar response to what is observed in vivo. The purpose of this review is to present the evolution from organ-on-chip to body-on-chip, examine their current use for drug testing and discuss their advantages and future challenges they will face in order to become an essential pillar of pharmaceutical research.