Abstract

Disturbed blood flow has been increasingly recognized for its critical role in platelet aggregation and thrombosis. Microfluidics with hump shaped contractions have been developed to mimic microvascular stenosis and recapitulate the prothrombotic effect of flow disturbance. However the physical determinants of microfluidic hemodynamics are not completely defined. Here, we report a refined computational fluid dynamics (CFD) simulation approach to map the shear rate (γ) and wall shear stress (τ) distribution in the stenotic region at high accuracy. Using ultra-fine meshing with sensitivity verification, our CFD results show that the stenosis level (S) is dominant over the bulk shear rate (γ0) and contraction angle (α) in determining γ and τ distribution at stenosis. In contrast, α plays a significant role in governing the shear rate gradient (γ′) distribution while it exhibits subtle effects on the peak γ. To investigate the viscosity effect, we employ a Generalized Power-Law model to simulate blood flow as a non-Newtonian fluid, showing negligible difference in the γ distribution when compared with Newtonian simulation with water medium. Together, our refined CFD method represents a comprehensive approach to examine microfluidic hemodynamics in three dimensions and guide microfabrication designs. Combining this with hematological experiments promises to advance understandings of the rheological effect in thrombosis and platelet mechanobiology.

Highlights

  • Disturbed blood flow has been increasingly recognized for its critical role in platelet aggregation and thrombosis

  • We present an ultra-fine computational fluid dynamics (CFD) study to map hemodynamic profiles for stenosis microfluidic models of thrombosis, and address the above concerns with mesh sensitivity verification and analytical validation

  • Τmax is similar on both eccentric (Fig. 2A) and concentric (Fig. 2E) stenosis microfluidic wall with 7% difference, a higher τ distribution is observed at the ceiling of the eccentric stenosis, which could lead to higher probabilities of vessel d­ amage[48]

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Summary

Introduction

Disturbed blood flow has been increasingly recognized for its critical role in platelet aggregation and thrombosis. Previous studies have justified these stenosis microfluidic models of thrombosis which have been well characterized and validated ­experimentally[6,7,13,16,38,40], demonstrating the shear rate gradient effects on platelet aggregation in blood flow disturbance. The detailed rheological mechanisms, or the exact τ, γ and γ′ thresholds that trigger such biomechanical platelet aggregation are incompletely understood In this context, CFD simulation represents the first step in revealing the hemodynamic profile within disturbed blood flow and correlating with experimental results of thrombotic response

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