Engineering microfluidic devices to mimic signaling cascades in continuous-flow cell culture as multiorgan microphysiological systems

The inability of traditional pre-clinical cell culture and animal models to accurately replicate human diseases and drug toxicities leads to a significant halt in the advancement of effective treatment strategies, in addition to financial losses. This, combined with the rise in ethical concerns about animal welfare, highlights the need for alternative and more realistic representations of human physiology. Microfluidics-based multiorgan microphysiological systems present a promising avenue for studying human body homeostasis, and have the potential to revolutionize translational research by creating new opportunities to comprehend systemic diseases and develop personalized medicine. In this review, we describe important design and operational considerations for engineering microfluidic devices mimicking tissue/organ “cross-talk” for in vitro drug disposition and safety assessments, as well as in disease modeling. We conducted a meticulous analysis of relevant articles and calculated crucial parameters, like the Reynolds number and shear stress, to compare the operational characteristics of different microfluidic devices. Additionally, we provide the reader with perspectives on the current limitations, insights to address the pending issues, and describe future opportunities of these technologies in the clinical setting.