The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Gerhard Gompper - One of the best experts on this subject based on the ideXlab platform.
-
understanding particle Margination in blood flow a step toward optimized drug delivery systems
Medical Engineering & Physics, 2016Co-Authors: Kathrin Muller, Dmitry A. Fedosov, Gerhard GompperAbstract:Targeted delivery of drugs and imaging agents is very promising to develop new strategies for the treatment of various diseases such as cancer. For an efficient targeted adhesion, the particles have to migrate toward the walls in blood flow - a process referred to as Margination. Due to a huge diversity of available carriers, a good understanding of their Margination properties in blood flow depending on various flow conditions and particle properties is required. We employ a particle-based mesoscopic hydrodynamic simulation approach to investigate the Margination of different carriers for a wide range of hematocrits (volume fraction of red blood cells) and flow rates. Our results show that Margination strongly depends on the thickness of the available free space close to the wall, the so-called red blood cell-free layer (RBC-FL), in comparison to the carrier size. The carriers with a few micrometers in size are comparable with the RBC-FL thickness and marginate better than their sub-micrometer counterparts. Deformable carriers, in general, show worse Margination properties than rigid particles. Particle Margination is also found to be most pronounced in small channels with a characteristic size comparable to blood capillaries. Finally, different Margination mechanisms are discussed.
-
Margination of micro and nano particles in blood flow and its effect on drug delivery
Scientific Reports, 2015Co-Authors: Kathrin Muller, Dmitry A. Fedosov, Gerhard GompperAbstract:Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their Margination properties (migration toward walls) in the microvasculature. To investigate Margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle Margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the Margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better Margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
-
White blood cell Margination in microcirculation
Soft Matter, 2014Co-Authors: Dmitry A. Fedosov, Gerhard GompperAbstract:Proper functioning of white blood cells is not possible without their ability to adhere to vascular endothelium, which may occur only if they are close enough to vessel walls. To facilitate the adhesion, white blood cells migrate toward the vessel walls in blood flow through a process called Margination. The Margination of white cells depends on a number of conditions including local hematocrit, flow rate, red blood cell aggregation, and the deformability of both red and white cells. To better understand the Margination process of white blood cells, we employ mesoscopic hydrodynamic simulations of a three-dimensional model of blood flow, which has been previously shown to capture quantitatively realistic blood flow properties and rheology. The Margination properties of white blood cells are studied for a wide range of hematocrit values and flow conditions. Efficient white blood cell Margination is found in an intermediate range of hematocrit values of Ht ≈ 0.2–0.4 and at relatively low flow rates, characteristic of the venular part of microcirculation. In addition, aggregation interactions between red blood cells lead to enhanced white-blood-cell Margination. This simulation study provides a quantitative description of the Margination of white blood cells, and is also highly relevant for the Margination of particles or cells of similar size such as circulating tumor cells.
-
Margination of micro and nano particles in blood flow and its effect on drug
2014Co-Authors: Dmitry A. Fedosov, Gerhard GompperAbstract:Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their Margination properties (migration toward walls) in the microvasculature. To investigate Margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle Margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the Margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better Margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
-
Margination of micro and nano particles in blood flow and its effect on the efficiency of drug delivery
2014Co-Authors: Kathrin Muller, Gerhard Gompper, D A Ferosov, Th MicroAbstract:Drug delivery by various microand nano-carriers offers the possibility of controlled transport of pharmaceuticals to targeted sites (e.g., cancerous tissue). Even though the fabrication of carriers of different sizes and shapes with a number of functionalities has made much progress in the last decade, their delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of microand nano-carriers in blood flow is strongly affected by their distribution within the vessel cross-section. To investigate the adhesion potential of carriers of different shapes and sizes, we employ mesoscopic hydrodynamic simulations of blood flow in order to predict Margination of carriers or their migration properties toward vessel walls. The Margination of carriers is studied for a wide range of hematocrit values, and flow rates, using a two-dimensional blood-flow model. Two different particle shapes (spherical and ellipsoidal) and various sizes, ranging from about hundred nanometers to several micrometers, are considered. We find that the Margination properties of particles worsen with decreasing carrier size. Spherical particles yield slightly better Margination than ellipsoidal particles; however, adhesion of ellipsoidal carriers is expected to be superior due to a larger area for adhesive interactions. As a conclusion, micron-size ellipsoidal particles seem to be favorable for drug delivery in comparison to sub-micron particles and spherically shaped carriers.
Mauro Ferrari - One of the best experts on this subject based on the ideXlab platform.
-
red blood cells affect the Margination of microparticles in synthetic microcapillaries and intravital microcirculation as a function of their size and shape
Journal of Controlled Release, 2015Co-Authors: Rosa Dapolito, Mauro Ferrari, Giovanna Tomaiuolo, Francesca Taraballi, Silvia Minardi, Dickson K Kirui, Xuewu Liu, Armando Cevenini, Roberto Palomba, Francesco SalvatoreAbstract:A key step in particle-based drug delivery throughmicrocirculation is particlemigration from blood flow to vesselwalls, also known as “Margination”,which promotes particle contact and adhesion to the vesselwall. Margination and adhesion should be independently addressed as two distinct phenomena, considering that the former is a fundamental prerequisite to achieve particle adhesion and subsequent extravasation. Although Margination has beenmodeled by numerical simulations and investigated inmodel systems in vitro, experimental studies including red blood cells (RBCs) are lacking. Here, we evaluate the effect of RBCs on Margination through microfluidic studies in vitro and by intravital microscopy in vivo.We showthatMargination,which is almost absent when particles are suspended in a cell-free medium, is drastically enhanced by RBCs. This effect is size- and shape-dependent, larger spherical/discoid particles being more effectively marginated both in vitro and in vivo. Our findings can be explained by the collision of particles with RBCs that induces the drifting of the particles towards the vessel walls where they become trapped in the cell-free layer. These results are relevant for the design of drug delivery strategies based on systemically administered carriers.
-
the Margination propensity of spherical particles for vascular targeting in the microcirculation
Journal of Nanobiotechnology, 2008Co-Authors: Francesco Gentile, Mauro Ferrari, Antonio Curcio, Ciro Indolfi, Paolo DecuzziAbstract:The propensity of circulating particles to drift laterally towards the vessel walls (Margination) in the microcirculation has been experimentally studied using a parallel plate flow chamber. Fluorescent polystyrene particles, with a relative density to water of just 50 g/cm3comparable with that of liposomal or polymeric nanoparticles used in drug delivery and bio-imaging, have been used with a diameter spanning over three order of magnitudes from 50 nm up to 10 μm. The number of particles marginating per unit surface have been measured through confocal fluorescent microscopy for a horizontal chamber, and the corresponding total volume of particles has been calculated. Scaling laws have been derived as a function of the particle diameter d. In horizontal capillaries, Margination is mainly due to the gravitational force for particles with d > 200 nm and increases with d4; whereas for smaller particles increases with d3. In vertical capillaries, since the particles are heavier than the fluid they would tend to marginate towards the walls in downward flows and towards the center in upward flows, with increasing with d9/2. However, the Margination in vertical capillaries is predicted to be much smaller than in horizontal capillaries. These results suggest that, for particles circulating in an external field of volume forces (gravitation or magnetic), the strategy of using larger particles designed to marginate and adhere firmly to the vascular walls under flow could be more effective than that of using particles sufficiently small (d < 200 nm) to hopefully cross a discontinuous endothelium.
-
the effect of shape on the Margination dynamics of non neutrally buoyant particles in two dimensional shear flows
Journal of Biomechanics, 2008Co-Authors: Francesco Gentile, Mauro Ferrari, Xuewu Liu, Ciro Chiappini, Daniel Fine, Rohan Bhavane, M S Peluccio, Mark Mingcheng ChengAbstract:Abstract The Margination dynamics of microparticles with different shapes has been analyzed within a laminar flow mimicking the hydrodynamic conditions in the microcirculation. Silica spherical particles, quasi-hemispherical and discoidal silicon particles have been perfused in a parallel plate flow chamber. The effect of the shape and density on their Margination propensity has been investigated at different physiologically relevant shear rates S. Simple scaling laws have been derived showing that the number n of marginating particles scales as S - 0.63 for the spheres; S - 0.85 for discoidal and S - 1 for quasi-hemispherical particles, regardless of their density and size. Within the range considered for the shear rate, discoidal particles marginate in a larger number compared to quasi-hemispherical and spherical particles. These results may be of interest in drug delivery and bio-imaging applications, where particles are expected to drift towards and interact with the walls of the blood vessels.
-
a theoretical model for the Margination of particles within blood vessels
Annals of Biomedical Engineering, 2005Co-Authors: Paolo Decuzzi, Stephen Lee, Bharat Bhushan, Mauro FerrariAbstract:The Margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The Margination speed and the time for Margination t s have been estimated as a function of the density of the particle relative to blood Δ ρ, the Hamaker constant A and radius R of the particle. A critical radius R c exists for which the Margination time t s has a maximum, which is influenced by both Δ ρ and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate Margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize Margination and increase their circulation time.
Haosheng Chen - One of the best experts on this subject based on the ideXlab platform.
-
Margination mechanism of stiffened red blood cell in microchannel with different cross section shapes
Microfluidics and Nanofluidics, 2019Co-Authors: Yuanyuan Chen, Haosheng ChenAbstract:An investigation of red blood cells (RBCs) Margination’s dependence on channel cross-section shape is presented. The irregularity of the vascular cross-section has been proved to satisfy the condition for stiffened RBCs to perform Margination in vivo, while the effect of channel geometry along channel width on cell Margination has not been revealed. To illustrate this problem, RBCs’ flowing behaviors in three different microchannels with cross-section of circular, rectangular and irregular are investigated, the forces acted on normal and stiffened RBCs are analyzed and calculated, the motions of RBCs are simulated, and the combined effect of channel geometry and fluid property is demonstrated. The stiffened RBCs are found to perform Margination in rectangular and irregular channel with viscoelastic fluid, while not in circular channel under the same fluid condition. Furthermore, the importance of fluid viscoelasticity to cell Margination is demonstrated in different microchannel. Our findings might offer some new insights to design microfluidic devices for cell-sorting technology and drug delivery system with high efficiency.
-
Margination of stiffened red blood cells regulated by vessel geometry
Scientific Reports, 2017Co-Authors: Yuanyuan Chen, Jiandi Wan, Haosheng ChenAbstract:Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the Margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the Margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated Margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.
Omolola Eniolaadefeso - One of the best experts on this subject based on the ideXlab platform.
-
the influence of red blood cell deformability on hematocrit profiles and platelet Margination
PLOS Computational Biology, 2020Co-Authors: Benjamin Czaja, Mario Gutierrez, Gabor Zavodszky, David De Kanter, Alfons G Hoekstra, Omolola EniolaadefesoAbstract:The influence of red blood cell (RBC) deformability in whole blood on platelet Margination is investigated using confocal microscopy measurements of flowing human blood and cell resolved blood flow simulations. Fluorescent platelet concentrations at the wall of a glass chamber are measured using confocal microscopy with flowing human blood containing varying healthy-to-stiff RBC fractions. A decrease is observed in the fluorescent platelet signal at the wall due to the increase of stiffened RBCs in flow, suggesting a decrease of platelet Margination due to an increased fraction of stiffened RBCs present in the flow. In order to resolve the influence of stiffened RBCs on platelet concentration at the channel wall, cell-pair and bulk flow simulations are performed. For homogeneous collisions between RBC pairs, a decrease in final displacement after a collision with increasing membrane stiffness is observed. In heterogeneous collisions between healthy and stiff RBC pairs, it is found that the stiffened RBC is displaced most. The influence of RBC deformability on collisions between RBCs and platelets was found to be negligible due to their size and mass difference. For a straight vessel geometry with varying healthy-to-stiff RBC ratios, a decrease was observed in the red blood cell-free layer and platelet Margination due to an increase in stiffened RBCs present in flow.
-
presence of rigid red blood cells in blood flow interferes with the vascular wall adhesion of leukocytes
Langmuir, 2018Co-Authors: Mario Gutierrez, Margaret B Fish, Alexander W Golinski, Omolola EniolaadefesoAbstract:The symptoms of many blood diseases can often be attributed to irregularities in cellular dynamics produced by abnormalities in blood cells, particularly red blood cells (RBCs). Contingent on the disease and its severity, RBCs can be afflicted with increased membrane rigidity as seen in malaria and sickle cell disease. Despite this understanding, little experimental work has been conducted toward understanding the effect of RBC rigidity on cellular dynamics in physiologic blood flow. Though many have computationally modeled complex blood flow to postulate how RBC rigidity may disrupt normal hemodynamics, to date, there lacks a clear understanding of how rigid RBCs affect the blood cell segregation behavior in blood flow, known as Margination, and the resulting change in the adhesion of white blood cells (WBCs). In this work, we utilized an in vitro blood flow model to examine how different RBC rigidities and volume fractions of rigid RBCs impact cell Margination and the downstream effect on white blood ce...
-
the Margination propensity of ellipsoidal micro nanoparticles to the endothelium in human blood flow
Biomaterials, 2013Co-Authors: Alex J Thompson, Eric M Mastria, Omolola EniolaadefesoAbstract:Particle shape is becoming increasingly recognized as an important parameter for the development of vascular-targeted carriers (VTCs) for disease treatment and diagnosis. However, limited research exists that investigates how particle shape coupled with hemodynamics affects VTC Margination (localization and adhesion). In this study, we investigate the effects of particle shape parameters (volume, aspect ratio, axis length) on the Margination efficacy of targeted spheres and prolate ellipsoids (rods) to an inflamed endothelial wall from human blood flow in an in vitro model of human vasculature. Overall, particles with 2 μm equivalent spherical diameters (ESD) display higher Margination than particles with either 1 μm or 500 nm ESDs. Interestingly, rod-shaped microparticles (1 μm or 2 μm ESD) with high aspect ratios display significantly improved Margination compared to spheres of equal volume, particularly under high shear rates and disturbed flow profiles. Nanorods (500 nm ESD), even with high aspect ratio, do not display enhanced Margination compared to that of equivalent spheres, which suggests that nanorods, like nanospheres, display minimal Margination due to their inability to effectively localize to the vessel wall in the presence of RBCs.
Dmitry A. Fedosov - One of the best experts on this subject based on the ideXlab platform.
-
understanding particle Margination in blood flow a step toward optimized drug delivery systems
Medical Engineering & Physics, 2016Co-Authors: Kathrin Muller, Dmitry A. Fedosov, Gerhard GompperAbstract:Targeted delivery of drugs and imaging agents is very promising to develop new strategies for the treatment of various diseases such as cancer. For an efficient targeted adhesion, the particles have to migrate toward the walls in blood flow - a process referred to as Margination. Due to a huge diversity of available carriers, a good understanding of their Margination properties in blood flow depending on various flow conditions and particle properties is required. We employ a particle-based mesoscopic hydrodynamic simulation approach to investigate the Margination of different carriers for a wide range of hematocrits (volume fraction of red blood cells) and flow rates. Our results show that Margination strongly depends on the thickness of the available free space close to the wall, the so-called red blood cell-free layer (RBC-FL), in comparison to the carrier size. The carriers with a few micrometers in size are comparable with the RBC-FL thickness and marginate better than their sub-micrometer counterparts. Deformable carriers, in general, show worse Margination properties than rigid particles. Particle Margination is also found to be most pronounced in small channels with a characteristic size comparable to blood capillaries. Finally, different Margination mechanisms are discussed.
-
Margination of micro and nano particles in blood flow and its effect on drug delivery
Scientific Reports, 2015Co-Authors: Kathrin Muller, Dmitry A. Fedosov, Gerhard GompperAbstract:Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their Margination properties (migration toward walls) in the microvasculature. To investigate Margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle Margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the Margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better Margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
-
White blood cell Margination in microcirculation
Soft Matter, 2014Co-Authors: Dmitry A. Fedosov, Gerhard GompperAbstract:Proper functioning of white blood cells is not possible without their ability to adhere to vascular endothelium, which may occur only if they are close enough to vessel walls. To facilitate the adhesion, white blood cells migrate toward the vessel walls in blood flow through a process called Margination. The Margination of white cells depends on a number of conditions including local hematocrit, flow rate, red blood cell aggregation, and the deformability of both red and white cells. To better understand the Margination process of white blood cells, we employ mesoscopic hydrodynamic simulations of a three-dimensional model of blood flow, which has been previously shown to capture quantitatively realistic blood flow properties and rheology. The Margination properties of white blood cells are studied for a wide range of hematocrit values and flow conditions. Efficient white blood cell Margination is found in an intermediate range of hematocrit values of Ht ≈ 0.2–0.4 and at relatively low flow rates, characteristic of the venular part of microcirculation. In addition, aggregation interactions between red blood cells lead to enhanced white-blood-cell Margination. This simulation study provides a quantitative description of the Margination of white blood cells, and is also highly relevant for the Margination of particles or cells of similar size such as circulating tumor cells.
-
Margination of micro and nano particles in blood flow and its effect on drug
2014Co-Authors: Dmitry A. Fedosov, Gerhard GompperAbstract:Drug delivery by micro- and nano-carriers enables controlled transport of pharmaceuticals to targeted sites. Even though carrier fabrication has made much progress recently, the delivery including controlled particle distribution and adhesion within the body remains a great challenge. The adhesion of carriers is strongly affected by their Margination properties (migration toward walls) in the microvasculature. To investigate Margination characteristics of carriers of different shapes and sizes and to elucidate the relevant physical mechanisms, we employ mesoscopic hydrodynamic simulations of blood flow. Particle Margination is studied for a wide range of hematocrit values, vessel sizes, and flow rates, using two- and three-dimensional models. The simulations show that the Margination properties of particles improve with increasing carrier size. Spherical particles yield slightly better Margination than ellipsoidal carriers; however, ellipsoidal particles exhibit a slower rotational dynamics near a wall favoring their adhesion. In conclusion, micron-sized ellipsoidal particles are favorable for drug delivery in comparison with sub-micron spherical particles.
-
Margination of white blood cells in microcapillary flow
Physical Review Letters, 2012Co-Authors: Dmitry A. Fedosov, Julia Fornleitner, Gerhard GompperAbstract:Margination of white blood cells (WBCs) towards vessel walls is an essential precondition for their efficient adhesion to the vascular endothelium. We perform numerical simulations with a two-dimensional blood flow model to investigate the dependence of WBC Margination on hydrodynamic interactions of blood cells with the vessel walls, as well as on their collective behavior and deformability. We find WBC Margination to be optimal in intermediate ranges of red blood cell (RBC) volume fractions and flow rates, while, beyond these ranges, it is substantially attenuated. RBC aggregation enhances WBC Margination, while WBC deformability reduces it. These results are combined in state diagrams, which identify WBC Margination for a wide range of flow and cell suspension conditions.