Microparticle shape effects on margination, near-wall dynamics and adhesion in a three-dimensional simulation of red blood cell suspension

Abstract

We present a 3D computational modeling study of the transport of micro-scale drug carriers modeled as microparticles of different shapes (spherical, oblate, and prolate) in whole blood represented as a suspension of deformable red blood cells. The objective is to quantify the effect of microparticle shapes on their margination, near-wall dynamics and adhesion. We observe that the near-wall accumulation is highest for oblate particles of moderate aspect ratio, followed by spherical particles, and lowest for very elongated prolate particles. The result is explained using micro-scale dynamics of individual particles, and their interaction with red blood cells. We observe that the orientation of microparticles in 3D space and the frequency of their collisions with red blood cells are the key factors affecting their margination. We show that due to repeated collisions with red blood cells in the presence of a bounding wall, the axes of revolution of oblate particles align near the plane of the shear flow, but those of prolate particles shift towards the vorticity axis with a wider distribution. Such specific orientations lead to more frequent collisions and a greater lateral drift for oblate particles than microspheres, but less frequent collisions and a reduced lateral drift for elongated prolate particles, resulting in the observed differences in their near-wall accumulation. Once marginated, the particle shape has an entirely different effect on the likelihood of making particle-wall contacts. We find that marginated prolate particles, due to their alignment along the vorticity axis and large angular fluctuations, are more likely to make contacts with the wall than spherical and oblate particles. We further simulate the adhesion between flowing microparticles and the wall in the presence of red blood cells, and observe that once wall contacts are established, the likelihood of firm adhesion is greater for disk-like particles, followed by elongated prolates, and microspheres. Consequently, this study suggests that the local hemorheological conditions near the targeted sites must be taken into consideration while selecting the optimum shape of micro-scale vascular drug carriers.

Direct Tracking of Particles and Quantification of Margination in Blood Flow

“…Likewise, a higher effective diffusivity, on the order of 15 mm 2 /s, was also observed in all of the blood cases relative to the water cases, which varied from 2-5 mm 2 /s. The larger fluctuations in v y and higher effective diffusivity in blood are probably caused by the collisions between particles and blood cells, consistent with arguments put forward in earlier simulation studies (20,35,37,53). Further, the calculation of M accounts for the actual velocity gradient and the absolute total number of particles that pass through the channel, offering a more robust way to compare data collected at different flow rates.…”

“…The higher the fluorescence intensity, the higher the margination propensity. In simulation studies, where the exact center of mass of particles is known, margination is conveniently defined as the number of particles at a given characteristic distance from the wall (e.g., the CFL thickness or adhesion distance) (15,20,21,23,37,49). In this study, each segment width was 9.5 mm, which is close to the CFL thickness, as shown in Fig.…”

“…Although adhesion and margination are related, evaluating margination based on the number of adhered particles could be further complicated by factors such as hydrodynamic drag, the densities of ligands and receptors grafted onto both the particle surface and the wall channel, the particle shape and contact orientation, and the particle size relative to the CFL (10,20,21). Particles may have detached from the wall due to collisions with blood cells or increasing wall shear rate.…”

“…This so-called enhanced permeability and retention effect (8) further opens up the possibility of delivering chemotherapeutic drugs passively and more specifically to tumor sites, thereby limiting any damage to healthy tissues (9,10). A number of recent experimental (3,7,(11)(12)(13)(14)(15)(16)(17) and theoretical (18)(19)(20)(21)(22)(23) studies have suggested that particles of certain sizes and shapes have a higher margination propensity. This would facilitate the diffusion of these particles into tumor sites by allowing them to reach the leaky blood vessel walls and, ultimately, the tumors.…”

“…First, all previous experimental studies, with only two exceptions (7,38), assessed margination propensity based on the number density, or, more precisely, the fluorescence intensity, of fluorescent particles that adhered to the channel wall after a particle suspension and subsequently a buffer solution passed through the channel (3,(11)(12)(13)(14)(16)(17)(18)39). Although adhesion is related to margination, adhesion also depends on other factors such as hydrodynamic drag, the densities of ligands and receptors grafted onto the particle surface and the wall channel, the particle shape and contact orientation, and the particle size relative to the CFL (10,16,17,20,21). In this work, the margination propensity was quantified based on the direct tracking of individual particles.…”