A physiologically realistic in vitro model of microvascular networks

Rosano, Jenna M.; Tousi, Nazanin; Scott, Robert C.; Krynska, Barbara; Rizzo, Victor; Prabhakarpandian, Balabhaskar; Pant, Kapil; Sundaram, S.; Kiani, Mohammad F.

doi:10.1007/s10544-009-9322-8

Cited by 83 publications

(74 citation statements)

References 33 publications

(44 reference statements)

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“…To determine whether shape-dependent cellular adhesion and internalization are also observed under flow conditions, experiments were performed using SMNs laden with RBE4 cells (29). RBE4 cells formed confluent monolayers within the SMNs ( Fig.…”

Section: Shear-dependent Adhesion Of Nanoparticles In Synthetic Micromentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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580

507

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Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rodshaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.biodistribution | morphology | SMN | cylinder | drug delivery

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Section: Shear-dependent Adhesion Of Nanoparticles In Synthetic Micromentioning

confidence: 99%

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Kolhar

Anselmo²,

Gupta³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

580

507

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“…This model also lacked the ability to apply localized cytokine challenge to the endothelial cell layer. Other vascular blood vessel systems did incorporate FSS, 14,15 yet were limited to testing a single condition at a time.…”

Section: B)mentioning

confidence: 99%

Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes

et al. 2016

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Endothelial cells form the inner lining of blood vessels and are exposed to various factors like hemodynamic conditions (shear stress, laminar, and turbulent flow), biochemical signals (cytokines), and communication with other cell types (smooth muscle cells, monocytes, platelets, etc.). Blood vessel functions are regulated by interactions among these factors. The occurrence of a pathological condition would lead to localized upregulation of cell adhesion molecules on the endothelial lining of the blood vessel. This process is promoted by circulating cytokines such as tumor necrosis factor-alpha, which leads to expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelial cell surface among other molecules. ICAM-1 is critical in regulating endothelial cell layer dynamic integrity and cytoskeletal remodeling and also mediates direct cell-cell interactions as part of inflammatory responses and wound healing. In this study, we developed a biomimetic blood vessel model by culturing confluent, flow aligned, endothelial cells in a microfluidic platform, and performed real time in situ characterization of flow mediated localized pro-inflammatory endothelial activation. The model mimics the physiological phenomenon of cytokine activation of endothelium from the tissue side and studies the heterogeneity in localized surface ICAM-1 expression and F-actin arrangement. Fluorescent antibody coated particles were used as imaging probes for identifying endothelial cell surface ICAM-1 expression. The binding properties of particles were evaluated under flow for two different particle sizes and antibody coating densities. This allowed the investigation of spatial resolution and accessibility of ICAM-1 molecules expressed on the endothelial cells, along with their sensitivity in receptor-ligand recognition and binding. This work has developed an in vitro blood vessel model that can integrate various heterogeneous factors to effectively mimic a complex endothelial microenvironment and can be potentially applied for relevant blood vessel mechanobiology studies. V C 2016 AIP Publishing LLC. [http://dx

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“…The ability to easily and tightly control biological conditions and the dynamic fluidic environment within the system enable microfluidics to be ideal tools for quantitatively analyzing hematologic and microvascular processes (11)(12)(13). Accordingly, researchers have recently applied microfluidic devices to study blood cell deformability, blood flow, and blood-endothelial cell interactions (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology

Tsai

Kita²,

Leach³

et al. 2012

J. Clin. Invest.

253

264

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In hematologic diseases, such as sickle cell disease (SCD) and hemolytic uremic syndrome (HUS), pathological biophysical interactions among blood cells, endothelial cells, and soluble factors lead to microvascular occlusion and thrombosis. Here, we report an in vitro "endothelialized" microfluidic microvasculature model that recapitulates and integrates this ensemble of pathophysiological processes. Under controlled flow conditions, the model enabled quantitative investigation of how biophysical alterations in hematologic disease collectively lead to microvascular occlusion and thrombosis. Using blood samples from patients with SCD, we investigated how the drug hydroxyurea quantitatively affects microvascular obstruction in SCD, an unresolved issue pivotal to understanding its clinical efficacy in such patients. In addition, we demonstrated that our microsystem can function as an in vitro model of HUS and showed that shear stress influences microvascular thrombosis/obstruction and the efficacy of the drug eptifibatide, which decreases platelet aggregation, in the context of HUS. These experiments establish the versatility and clinical relevance of our microvasculature-on-a-chip model as a biophysical assay of hematologic pathophysiology as well as a drug discovery platform.

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A physiologically realistic in vitro model of microvascular networks

Cited by 83 publications

References 33 publications

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Using shape effects to target antibody-coated nanoparticles to lung and brain endothelium

Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes

In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology

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