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Biofabrication. 2019 Nov 18. doi: 10.1088/1758-5090/ab5898. [Epub ahead of print]

Disturbed flow disrupts the blood-brain barrier in a 3D bifurcation model.

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Biomedical Engineering, Rowan University, Glassboro, New Jersey, UNITED STATES.
Biomedical Engineering , Rowan University, Glassboro, New Jersey, 08028-1700, UNITED STATES.
Bioengineering, Rice University, Houston, Texas, UNITED STATES.
Biomedical Engineering, Rowan University, Glassboro, UNITED STATES.
Department of Bioengineering, Rice University, Houston, Texas, UNITED STATES.
Biomedical Engineering, Rowan University, 201 Mullica Hill Rd, Glassboro, New Jersey, 08028, UNITED STATES.


The effect of disturbed flow profiles on the endothelium have been studied extensively in systemic vasculature, but less is known about the response of the blood-brain barrier (BBB) to these flow regimes. Here we investigate the effect of disturbed flow on the integrity of the BBB using a three-dimensional, perfusable bifurcation model consisting of a co-culture of endothelial cells with mural and glial cells. Experimental flow patterns predicted by computational fluid dynamics mimic in vivo flow regimes, specifically the presence of a recirculation zone immediately downstream of the bifurcation. Dextran permeability assays and immunostaining with markers for tight junctions show that barrier disruption is significantly greater in areas of disturbed flow compared to fully developed regions downstream of the bifurcation. Probing crosstalk between cell types suggests that disturbed flow causes barrier breakdown independent of endothelial-mural and endothelial-glial interaction. Overall, disturbed flow-induced disruption of the blood-brain barrier suggests that flow-mediated mechanisms may contribute to vascular pathologies in the central nervous system.


Blood-Brain Barrier; Fluid Dynamics; Vascular Model


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