Bio‐Mimicking Brain Vasculature to Investigate the Role of Heterogeneous Shear Stress in Regulating Barrier Integrity

A continuous, sealed endothelial membrane is essential for the blood–brain barrier (BBB) to protect neurons from toxins present in systemic circulation. Endothelial cells are critical sensors of the capillary environment, where factors like fluid shear stress (FSS) and systemic signaling molecules a...

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Veröffentlicht in:Advanced biology 2022-12, Vol.6 (12), p.e2200152-n/a
Hauptverfasser: Mehta, Ami, Desai, Anal, Rudd, David, Siddiqui, Ghizal, Nowell, Cameron J., Tong, Ziqiu, Creek, Darren J., Tayalia, Prakriti, Gandhi, Prasanna S., Voelcker, Nicolas H.
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container_issue 12
container_start_page e2200152
container_title Advanced biology
container_volume 6
creator Mehta, Ami
Desai, Anal
Rudd, David
Siddiqui, Ghizal
Nowell, Cameron J.
Tong, Ziqiu
Creek, Darren J.
Tayalia, Prakriti
Gandhi, Prasanna S.
Voelcker, Nicolas H.
description A continuous, sealed endothelial membrane is essential for the blood–brain barrier (BBB) to protect neurons from toxins present in systemic circulation. Endothelial cells are critical sensors of the capillary environment, where factors like fluid shear stress (FSS) and systemic signaling molecules activate intracellular pathways that either promote or disrupt the BBB. The brain vasculature exhibits complex heterogeneity across the bed, which is challenging to recapitulate in BBB microfluidic models with fixed dimensions and rectangular cross‐section microchannels. Here, a Cayley‐tree pattern, fabricated using lithography‐less, fluid shaping technique in a modified Hele‐Shaw cell is used to emulate the brain vasculature in a microfluidic chip. This geometry generates an inherent distribution of heterogeneous FSS, due to smooth variations in branch height and width. hCMEC/D3 endothelial cells cultured in the Cayley‐tree designed chip generate a 3D monolayer of brain endothelium with branching hierarchy, enabling the study of the effect of heterogeneous FSS on the brain endothelium. The model is employed to study neuroinflammatory conditions by stimulating the brain endothelium with tumor necrosis factor‐α under heterogeneous FSS conditions. The model has immense potential for studies involving drug transport across the BBB, which can be misrepresented in fixed dimension models. Fabrication of a lithography‐less Cayley‐tree pattern to generate a blood‐brain barrier‐on‐a‐chip. The shape of the microchannels in the Cayley‐tree pattern is semi‐elliptical with smooth variation in the height of the microchannels from the parent branch to daughter branches. Heterogeneous fluid shear stress is experienced by the cerebral endothelial cells across the branches of different generations within a single microfluidic device.
doi_str_mv 10.1002/adbi.202200152
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source MEDLINE; Access via Wiley Online Library
subjects biomimicry
Blood-Brain Barrier
blood–brain barrier‐on‐chip
Brain
Cayley‐tree pattern
Endothelial Cells - metabolism
Hele‐Shaw cell
heterogeneous fluid shear stress
Microfluidics
neuroinflammation
Stress, Mechanical
title Bio‐Mimicking Brain Vasculature to Investigate the Role of Heterogeneous Shear Stress in Regulating Barrier Integrity
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