Passive-Flow-Based MPS: Emerging Physiological Flow-Mimetic Platforms for Studying Effects of Flow on Single Tissues and Inter-tissue Interactions

Flow at various scales, such as perfusion flow and interstitial flow, is a critical component of the physiology of living systems. Microphysiological system (MPS), which is designed to mimic human physiology, needs to recapitulate various physiological flows to accurately reflect in vivo conditions. Most MPSs that simulate flows utilize a pump and tubing (pumped-based-flow MPS). However, these components have limitations that prevent them from recapitulating sophisticated physiological phenomena. Alternatively, passive-flow MPS can be used to recapitulate physiological flow on various scales without using pumps or tubing. This review presents recent developments in passive-flow-based MPS using various engineering approaches. To this end, engineering approaches that enable a passive-flow-based MPS to operate are summarized. Subsequently, representative examples of passive-flow-based MPS are reviewed under the criterion of whether they can recapitulate single-organ (tissue) or multi-organ (tissue) systems. It is our belief that passive-flow-based MPS will be widely used in a wide range of fields, such as human physiology research, analysis of pharmacokinetics and pharmacodynamics (PK/PD), and even space medicine research.