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These systems, however, lack the periodic fluctuations, or biorhythms, in the cellular microenvironment that effectively integrate \u201ctime\u201d into these culture platforms by providing physiological inputs necessary for cellular synchronization and circadian rhythms. Given the central role that circadian rhythms play in health and disease, this absence is puzzling. For example, cardiovascular disease, diabetes, osteoarthritis, and asthma, are just a few diseases with known circadian rhythm effects. Moreover, more than half of the top 100 selling drugs target the product of a circadian gene, and multiple clinical trials have retrospectively shown the impact of time-of-day dosing on improved outcomes and increased patient lifespan. The underlying reason conventional systems largely do not integrate temporal dynamics in vitro is because they either require the use of poorly scalable external flow control systems or manual fluid exchanges. 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