Bifurcations: Focal Points of Particle Adhesion in Microvascular Networks

Prabhakarpandian, Balabhaskar; Wang, Yi; Rea-Ramsey, Angela; Sundaram, S.; Kiani, Mohammad F.; Pant, Kapil

doi:10.1111/j.1549-8719.2011.00099.x

Cited by 32 publications

(36 citation statements)

References 34 publications

(41 reference statements)

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“…A programmable syringe pump (PHD 2000, Harvard Apparatus, MA) was used to inject the particles and the flow was set for a shear rate of 240 1/sec. Every 3 min, the flow was reduced by half reaching a final shear rate of 7.5 1/sec, similar to our previous studies (Doshi et al, 2010; Kolhar et al, 2013; Lamberti et al, 2013; Prabhakarpandian et al, 2011c, 2001; Sakhalkar et al, 2003). The new shear rate was maintained for 3 min to allow sufficient time for a statistically significant number of adhesion events to occur (Doshi et al, 2010; Kolhar et al, 2013; Lamberti et al, 2013; Prabhakarpandian et al, 2011c; Smith et al, 2014).…”

Section: Methodsmentioning

confidence: 68%

“…Previously, our group has shown that the presence or absence of endothelial cells and/or receptor concentrations on their surfaces, are not the driving forces behind the preferential adhesion patterns of neutrophils near bifurcations (Prabhakarpandian et al, 2011c; Rosano et al, 2009; Tousi et al, 2010). Similar to our previous results (Lamberti et al, 2013), the number of adherent particles/neutrophils in junction regions is statistically higher than in straight sections depending on local shear stress.…”

Section: Discussionmentioning

confidence: 97%

“…Our findings indicate that both functionalized particle and neutrophil adhesion increases with a larger bifurcation angle. The higher adhesion of particles/neutrophils at the larger bifurcation angle observed in SMNs is likely due to altered flow patterns, which lead to a higher interaction of particles/neutrophils with the walls (Prabhakarpandian et al, 2011c). Given the fact that neutrophil-endothelial cell interactions involve a much larger number of biochemical interactions compared to biotin-avidin interactions of the 7 µm rigid particles, it is interesting to note that as the bifurcation angle increases, differences between particle adhesion and neutrophil adhesion profiles becomes more pronounced.…”

Section: Discussionmentioning

confidence: 99%

“…In prior studies, we showed that adhesion efficiency of functionalized particles and leukocytes in vitro using synthetic microvascular networks (SMNs) mimicking the in vivo microvasculature and fluid flow conditions (Lamberti et al, 2014; Prabhakarpandian et al, 2011b) and leukocytes in in vivo vessels (Tousi et al, 2010) is significantly affected by geometric features of the vessels. Doshi et al (2010) showed that a simple bifurcating microfluidic flow chamber can be used to characterize the transport and adhesion dynamics of drug carrying particles.…”

Section: Introductionmentioning

confidence: 99%

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Adhesion patterns in the microvasculature are dependent on bifurcation angle

Lamberti

Soroush

Kiani

et al. 2015

Microvascular Research

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Particle adhesion in vivo is highly dependent on the microvascular environment comprising of unique anatomical, geometrical, physiological fluid flow conditions and cell-particle and cell-cell interactions. Hence, proper design of vascular-targeted drug carriers that efficiently deliver therapeutics to the targeted cells or tissue at effective concentrations must account for these complex conditions observed in vivo. In this study, we build upon our previous results with the goal of characterizing the effects of bifurcations and their corresponding angle on adhesion of functionalized particles and neutrophils to activated endothelium. Our hypothesis is that adhesion is significantly affected by the type of biochemical interactions between particles and vessel wall as well as the presence of bifurcations and their corresponding angle. Here, we investigate adhesion of functionalized particles (2 µm and 7 µm microparticles) to protein coated channels as well as adhesion of human neutrophils to human endothelial cells under various physiological flow conditions in microfluidic bifurcating channels comprising of different contained angles (30°, 60°, 90°, or 120°). Our findings indicate that both functionalized particle and neutrophil adhesion propensity increases with a larger bifurcation angle. Moreover, the difference in adhesion patterns of neutrophils and rigid, similar sized (7 µm) particles is more apparent in the junction regions with a larger contained angle. By selecting the right particle size range, enhanced targeted binding of vascular drug carriers can be achieved along with a higher efficacy at optimal drug dosage. Hence, vascular drug particle design needs to be tailored to account for higher binding propensity at larger bifurcation angles.

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Section: Methodsmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adhesion patterns in the microvasculature are dependent on bifurcation angle

Lamberti

Soroush

Kiani

et al. 2015

Microvascular Research

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“…These devices termed SynVivo-Synthetic Microvascular Networks (SMN) are developed using PDMS based soft-lithography process. SynVivo-SMN devices can be used to obtain shear adhesion map of cell/particle adhesion 22 , study targeted drug delivery 23 and have been validated against in vivo data [24][25] Representative Results Figure 1A shows a schematic and a bright field image of SynVivo-SMN device. Figure 1B shows the SynVivo-SMN device mounted on a glass slide.…”

Section: Introductionmentioning

confidence: 99%

Generation of Shear Adhesion Map Using SynVivo Synthetic Microvascular Networks

Prabhakarpandian

Pant

2014

JoVE

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Cell/particle adhesion assays are critical to understanding the biochemical interactions involved in disease pathophysiology and have important applications in the quest for the development of novel therapeutics. Assays using static conditions fail to capture the dependence of adhesion on shear, limiting their correlation with in vivo environment. Parallel plate flow chambers that quantify adhesion under physiological fluid flow need multiple experiments for the generation of a shear adhesion map. In addition, they do not represent the in vivo scale and morphology and require large volumes (~ml) of reagents for experiments. In this study, we demonstrate the generation of shear adhesion map from a single experiment using a microvascular network based microfluidic device, SynVivo-SMN. This device recreates the complex in vivo vasculature including geometric scale, morphological elements, flow features and cellular interactions in an in vitro format, thereby providing a biologically realistic environment for basic and applied research in cellular behavior, drug delivery, and drug discovery. The assay was demonstrated by studying the interaction of the 2 µm biotin-coated particles with avidin-coated surfaces of the microchip. The entire range of shear observed in the microvasculature is obtained in a single assay enabling adhesion vs. shear map for the particles under physiological conditions. Video LinkThe video component of this article can be found at

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Cellular Interactions of Liposomes and PISA Nanoparticles during Human Blood Flow in a Microvascular Network

Kelly

Wheatley

et al. 2020

Small

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Liposomes such as Doxil are currently used in clinics to achieve such benefits in cancer treatment while other lipid nanoparticles (LNP) carrying messenger RNA (mRNA) find potential use as safe and effective vaccines. [4-6] A relevant example is the recent approval of an mRNA LNP vaccine candidate by the U.S. Food and Drug Administration for the first clinical trial against the 2019 coronavirus (SARS-CoV-2). [7,8] In addition, polymeric nanoparticles have demonstrated a wide variety of applications ranging from drug and gene delivery to nanocarriers for imaging contrast agents and non-opioid drugs to treat chronic pain. [9-11] In the majority of these applications, nanoparticles first interact with human blood in blood vessels before reaching disease targets (tissues or cells). [12] For example, upon administering Doxil nanoparticles, they interact with human blood during circulation, and only a small proportion of these nanoparticles can accumulate in tumors. [13-15] While interactions of nanoparticles with cancer cells have been extensively studied, their interactions with healthy cells in human blood and blood vessels remain unclear as it is challenging to study. [16] Understanding such important A key concept in nanomedicine is encapsulating therapeutic or diagnostic agents inside nanoparticles to prolong blood circulation time and to enhance interactions with targeted cells. During circulation and depending on the selected application (e.g., cancer drug delivery or immune modulators), nanoparticles are required to possess low or high interactions with cells in human blood and blood vessels to minimize side effects or maximize delivery efficiency. However, analysis of cellular interactions in blood vessels is chal lenging and is not yet realized due to the diverse components of human blood and hemodynamic flow in blood vessels. Here, the first comprehensive method to analyze cellular interactions of both synthetic and commercially available nanoparticles under human blood flow conditions in a micro vascular network is developed. Importantly, this method allows to unravel the complex interplay of size, charge, and type of nanoparticles on their cellular associations under the dynamic flow of human blood. This method offers a unique platform to study complex interactions of any type of nanoparticles in human blood flow conditions and serves as a useful guideline for the rational design of liposomes and polymer nanoparticles for diverse applications in nanomedicine.

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Bifurcations: Focal Points of Particle Adhesion in Microvascular Networks

Cited by 32 publications

References 34 publications

Adhesion patterns in the microvasculature are dependent on bifurcation angle

Adhesion patterns in the microvasculature are dependent on bifurcation angle

Generation of Shear Adhesion Map Using SynVivo Synthetic Microvascular Networks

Cellular Interactions of Liposomes and PISA Nanoparticles during Human Blood Flow in a Microvascular Network

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