Rhythm on a chip: circadian entrainment in vitro is the next frontier in body-on-a chip technology

Organoids, bioprinted mini-tissues and body-on-a-chip technologies are poised to transform the practice of preclinical pharmacology, with a view to achieving better predictive value. We review the need for further refinement in static and dynamic biomechanical aspects of such microenvironments. Further consideration of the developments required in perfusion systems to enable delivery of an appropriate soluble microenvironment are argued. We place particular emphasis on a major deficiency in these systems, being the absence or aberrant circadian behaviour of cells used in such settings, and consider the technical challenges that are needing to be met in order to achieve rhythm-on-a-chip.