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theses

Computational modeling and simulation is considered to study the concurrent multiscale/multiphysics phenomena associated with cellular/particulate transport in microcirculatory blood flow. The model integrates microhydrodynamics of different blood cells, complexity of vascular geometry, and nanoscale adhesive interactions. A finite element method (FEM) is used to model the cell membrane deformation with high accuracy, and is coupled to the bulk flow motion via a front-tracking method. The geometric complexities are simulated using a sharp-interface immersed boundary method, and the molecular adhesion is coarse-grained via a Monte Carlo method. The following sequence of problems is addressed: (a) Hydrodynamic interaction between a platelet and a red blood cell (RBC) in a dilute suspension: 3D simulations of pairwise hydrodynamic interaction between a platelet and an RBC in a wall-bounded shear flow are conducted. The effects of different dynamics of the RBC, namely tank-treading and tumbling, and the proximity to the wall on platelet trajectories are quantified. Based on the numerical results, a mechanism of continual platelet drift towards the vessel wall is proposed. (b) Platelet transport and dynamics in blood flow: 3D simulations are considered to study the transport of platelets in semi-dense suspension of flowing RBCs. It is found that the local microstructure of RBC suspension provides a fast margination mechanism for platelets to drift towards the blood vessel wall. It is also shown that the anisotropic diffusion of platelets contributes to the formation of platelet clusters, and may act as a hydrodynamic precursor to blood clot formation. (c) Microparticle shape effects on their transport and dynamics in blood flow: The shape effect of microscale targeting drug carriers modeled as platelet-sized microparticles on their margination, near-wall dynamics, and adhesion is quantified and explained by individual particle dynamics and interaction with RBCs. It is shown that the particle shape has entirely different effects on different stages of margination/adhesion cascade. It is suggested that the local hemorheological conditions of the targeted site should be taken into account while selecting the optimum shape for microvascular drug carriers. (d) Blood flow in stenosed microvessels: 3D simulations of cellular motion through stenosed microvessels are considered. The Fahraeus-Lindqvist effect is shown to be significantly enhanced, due to the asymmetric distribution of the RBCs caused by the stenosis geometry. Such asymmetry together with the discrete motion of cells are demonstrated to cause an asymmetry in the average as well as the time-dependent flow characteristics along the length of stenosis. It is concluded that the flow physics and its physiological consequences are significantly different in micro- versus macrovascular stenosis. (e) Adhesion of microparticles in microvessels – role of RBCs and microparticle deformability: 3D simulations of the adhesion of deformable drug carrier particles in the flow of semi-dense RBC suspension through microvessels are conducted. It is shown that both the presence of RBCs and the particle deformability have a dual role in microparticle adhesion. During the initial formation of adhesive bonds, the RBCs have an enhancing effect while the effect of particle deformation is adverse. In contrast, during the subsequent adhesive rolling of microparticles, the RBCs have an adverse effect while the particle deformation improves stable adhesive rolling motion. It is concluded that to efficiently benefit from the advantages of deformable particles in biomedical targeting, the local blood flow characteristics of the targeted site must be taken into account.

ETD_6666

Ph.D.

Includes bibliographical references

by Koohyar Vahidkhah

doi:10.7282/T34T6MC8

ETD doctoral

The author owns the copyright to this work.