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Description
The flow-induced morphology of platelet aggregates is emerging as a key mechanobiological indicator of thrombotic risk and coagulation disorders. Thrombus formation is a dynamic process in which flowing platelets adhere to a pro-thrombotic surface, aggregate, and grow, progressively reshaping the vessel wall topography and altering the local hemodynamic environment. While shear forces and hematocrit are known to influence platelet transport and adhesion, their coupled role during thrombus growth, which introduces evolving geometrical heterogeneities, remains poorly understood. The aim of this study is to elucidate how shear flow and hematocrit jointly regulate thrombus evolution under flow by combining blood-on-chip experiments with resolved numerical simulations.
Microfluidic experiments were performed in collagen-coated blood-on-chip devices using human blood at varying hematocrit and wall shear rate. Real-time platelet adhesion and aggregation were imaged using high-resolution confocal microscopy. Advanced 3D image analysis enabled a quantitative and detailed characterization of thrombus morphology and structural features associated with thrombus growth and stability. Resolved three-dimensional simulations of blood flow in microchannels featuring a sinusoidal wall were used to investigate how aggregate-induced surface heterogeneities reshape local hemodynamics and platelet margination. The sinusoidal wall was used as a simplified model of mural platelet aggregates observed in microfluidic experiments. Blood was modeled as a suspension of deformable red blood cells and nearly rigid platelets. A combined lattice-Boltzmann, immersed-boundary, and finite-element approach was employed to resolve cell dynamics, cell-free layer formation, and platelet margination near the sinusoidal wall.
Microfluidic experiments show that increasing hematocrit enhances platelet surface coverage promoting the stabilization of platelet aggregate adhesion to the wall. In contrast, shear rate primarily controls aggregate elongation and alignment along the flow direction. Numerical simulations reveal that aggregate-induced surface heterogeneities generate spatial variations in cell-free layer thickness and local shear rate. Platelet margination is mainly governed by hematocrit and is most effective where the local cell-free layer thickness matches platelet size. Shear rate, instead, plays a secondary role in platelet margination but strongly modulates local shear rate gradients around the aggregate, suggesting a dominant influence on platelet adhesion dynamics.
Overall, this work presents a quantitative microfluidic framework to study thrombus evolution under flow, providing a direct link between platelet aggregate morphology, local hemodynamics and blood-cell transport.