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Critical considerations for the design of multi-organ microphysiological systems (MPS)



Mridu Malik, Yang Yang, Parinaz Fathi, Gretchen Mahler, Mandy Esch


The process of identifying new drugs and getting them approved for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The reliability of data obtained with animal models has been called into question because subsequent clinical studies often reveal lower than expected efficacy and also higher drug toxicity. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used in drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ-scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With a large number of MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate them. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.
Frontiers in Cell and Developmental Biology


microphysiological systems, MPS, body-on-a-chip, organ-on-a-chip, microifluidics


Malik, M. , Yang, Y. , Fathi, P. , Mahler, G. and Esch, M. (2021), Critical considerations for the design of multi-organ microphysiological systems (MPS), Frontiers in Cell and Developmental Biology, [online],, (Accessed May 26, 2024)


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Created September 9, 2021, Updated November 29, 2022