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Journal of Healthcare Engineering
Volume 2017, Article ID 5740975, 10 pages
https://doi.org/10.1155/2017/5740975
Research Article

Gene Expression Changes in Long-Term In Vitro Human Blood-Brain Barrier Models and Their Dependence on a Transwell Scaffold Material

1American Society for Engineering Education Postdoctoral Fellowship Program, U.S. Naval Research Laboratory, Washington, DC, USA
2Chemistry Division, U.S. Naval Research Laboratory, Washington, DC, USA
3National Research Council Postdoctoral Fellowship Program, U.S. Naval Research Laboratory, Washington, DC, USA
4Defense Advanced Research Projects Agency, Arlington, VA, USA

Correspondence should be addressed to Russell K. Pirlo; lim.yvan.lrn@olriP.llessuR

Received 20 June 2017; Revised 19 September 2017; Accepted 12 October 2017; Published 29 November 2017

Academic Editor: George Stan

Copyright © 2017 Joel D. Gaston et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Disruption of the blood-brain barrier (BBB) is the hallmark of many neurovascular disorders, making it a critically important focus for therapeutic options. However, testing the effects of either drugs or pathological agents is difficult due to the potentially damaging consequences of altering the normal brain microenvironment. Recently, in vitro coculture tissue models have been developed as an alternative to animal testing. Despite low cost, these platforms use synthetic scaffolds which prevent normal barrier architecture, cellular crosstalk, and tissue remodeling. We created a biodegradable electrospun gelatin mat “biopaper” (BP) as a scaffold material for an endothelial/astrocyte coculture model allowing cell-cell contact and crosstalk. To compare the BP and traditional models, we investigated the expression of 27 genes involved in BBB permeability, cellular function, and endothelial junctions at different time points. Gene expression levels demonstrated higher expression of transcripts involved in endothelial junction formation, including TJP2 and CDH5, in the BP model. The traditional model had higher expression of genes associated with extracellular matrix-associated proteins, including SPARC and COL4A1. Overall, the results demonstrate that the BP coculture model is more representative of a healthy BBB state, though both models have advantages that may be useful in disease modeling.