Abstract

The emerging profile of blood flow and the cross-sectional distribution of blood cells have far reaching biological consequences in various diseases and vital internal processes, such as platelet adhesion. The effects of several essential blood flow parameters, such as red blood cell free layer width, wall shear rate, and hematocrit on platelet adhesion were previously explored to great lengths in straight geometries. In the current work, the effects of channel curvature on cellular blood flow are investigated by simulating the accurate cellular movement and interaction of red blood cells and platelets in a half-arc channel for multiple wall shear rate and hematocrit values. The results show significant differences in the emerging shear rate values and distributions between the inner and outer arc of the channel curve, while the cell distributions remain predominantly uninfluenced. The simulation predictions are also compared to experimental platelet adhesion in a similar curved geometry. The inner side of the arc shows elevated platelet adhesion intensity at high wall shear rate, which correlates with increased shear rate and shear rate gradient sites in the simulation. Furthermore, since the platelet availability for binding seems uninfluenced by the curvature, these effects might influence the binding mechanics rather than the probability. The presence of elongational flows is detected in the simulations and the link to increased platelet adhesion is discussed in the experimental results.

Highlights

  • The effects of curved vessel geometry on blood flow were investigated thoroughly from a macroscopic viewpoint,[2,31] where blood is approximated as a continuum fluid and the biological implications are commonly linked to the magnitude or inhomogeneity of wall shear stress

  • To study the impact of altered hemodynamic conditions generated in a curved vessel geometry on PLT function, the thrombi coverage on the described collagen coated MFD surface is evaluated after blood perfusion

  • The effect subsides into the outlet section (III.) with no significant difference outside of the increased standard error of the mean (SEM) error margin compared to the inlet section

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Summary

INTRODUCTION

The effects of curved vessel geometry on blood flow were investigated thoroughly from a macroscopic viewpoint,[2,31] where blood is approximated as a continuum fluid and the biological implications (often in connection to cardiovascular diseases) are commonly linked to the magnitude or inhomogeneity of wall shear stress. This process, which occurs both in physiological hemostasis, as well as pathological thrombosis, is found to be highly shear dependent and sensitive to hydrodynamic alterations.[11,19] The shift of initially even shear gradients, e.g. caused by a sudden reduction in vessel diameter (vasoconstriction), leads to the presence of so called elongational flows These flow fields, defined by exerting tensile forces, are found to promote PLT adhesion under certain conditions, enabled by the mediation of prominent plasma molecule von Willebrand factor (vWF).[13,23] PLT adhesion is known to depend on the presence of a CFL29 as well as the level of hematocrit.[24]. A comparison to in vitro assays in a similar curved microfluidic geometry is presented as well and the possible implications of elongational flow in vessel curvature on PLT adhesion are discussed

MATERIALS AND METHODS
Evaluation Method
In Vitro Results
In Silico Results
DISCUSSION
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