A Reconfigurable In Vitro Model for Studying the Blood–Brain Barrier

Publication Date

2-1-2020

Document Type

Article

Publication Title

Annals of Biomedical Engineering

Volume

48

Issue

2

DOI

10.1007/s10439-019-02405-y

First Page

780

Last Page

793

Abstract

Much of what is currently known about the role of the blood–brain barrier (BBB) in regulating the passage of chemicals from the blood stream to the central nervous system (CNS) comes from animal in vivo models (requiring extrapolation to human relevance) and 2D static in vitro systems, which fail to capture the rich cell–cell and cell–matrix interactions of the dynamic 3D in vivo tissue microenvironment. In this work we have developed a BBB platform that allows for a high degree of customization in cellular composition, cellular orientation, and physiologically-relevant fluid dynamics. The system characterized and presented in this study reproduces key characteristics of a BBB model (e.g. tight junctions, efflux pumps) allowing for the formation of a selective and functional barrier. We demonstrate that our in vitro BBB is responsive to both biochemical and mechanical cues. This model further allows for culture of a CNS-like space around the BBB. The design of this platform is a valuable tool for studying BBB function as well as for screening of novel therapeutics.

Funding Number

LLNL-JRNL-758697

Funding Sponsor

U.S. Department of Energy

Keywords

Blood–brain barrier, Endothelial cells, Organ-on-a-chip

Department

Biomedical Engineering

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