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

Abstract

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

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

“…Details on cell shape, F-actin filament alignment, and reorganization on exposure to FSS in this device have been reported in our previous work. 30 F-actin realignment to flow for BAOECs happens within 4 h in the BBV model (details in our previous work), and our permeability assay is performed 6 h after applying FSS in order to consider this.…”

“…30 The upper and lower channels were cast out of Sylgard 184 PDMS (Dow Corning Corp.). The upper channel was 20 mm long, 350 lm wide, and 100 lm tall, and the lower channel was 5 mm long, 1000 lm wide, and 100 lm tall.…”

Deconstructing Immune Microenvironments of Lymphoid Tissues for Reverse Engineering

“…Then, complete transendothelial migration assessment was made possible through the use of Transwells with LECs attached to the bottom of the membrane instead, as transmigration is in the direction of the basal side to the apical end. Vascular research has also led to the development of various types of microfluidic biomimetic models that can be used to study the circulatory system …”

“…While microfluidics technology is attractive, several key aspects have to be considered when coculturing ECs with immune cells. The chemical makeup of the microenvironment, a blood or lymph substitute circulating through biomimetic devices, needs to be regulated to contain the appropriate concentration of biological and chemical mediators to mimic the physiological or pathophysiological state of interest . In addition to requiring a constant supply of fresh medium to remain viable, cell phenotypes and interactions will be regulated by soluble factors.…”

Artificial Circulatory Model for Analysis of Human and Artificial Vessels

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