3M engineering approaches to combat high-shear thrombosis: Integrating modeling, microfluidics, and mechanobiology

Arterial thrombosis remains a significant global health concern, with shear-induced platelet aggregation (SIPA) playing a crucial role. This review focuses on the integration of three key engineering approaches-Computational Modeling Micro- fluidics and Mechanobiology (3 M)-in understanding and combating high-shear thrombosis. We discuss the biomechanical mechanisms of SIPA, highlighting how platelet mechanoreceptors and von Willebrand factor interactions drive thrombosis under pathological flow conditions. Through computational fluid dynamics (CFD), key hemodynamic metrics including time-averaged wall shear stress, oscillatory shear index, and relative residence time have been developed to predict thrombosis risk. Microfluidic platforms, ranging from straight channels to stenotic geometries, provide insights into platelet behavior under various shear conditions while enabling rapid screening of antithrombotic therapies. The integration of these experimental approaches with CFD analysis offers powerful tools for predicting thrombosis risk and optimizing device designs, particularly in mechanical circulatory support devices (MCSDs). Recent advances in mechanobiology have revealed how mechanical forces trigger cellular responses through membrane damage and mechanosensitive channels, offering new therapeutic targets. This review underscores how the synergy between these 3 M engineering approaches advances our understanding of the complex interplay between hemodynamics and thrombosis, paving the way for improved antithrombotic therapies and medical device designs essential to optimizing MCSDs, such as left ventricular assist devices and extracorporeal membrane oxygenators.