title: Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor.
abstract: The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.
authors.forename: Jacquelyn A
authors.initials: JA
authors.lastname: Brown
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pensabene
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Markov
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Allwardt
authors.affiliation: Department of Neurology, Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt Center in Molecular Toxicology, Vanderbilt University , Nashville, Tennessee 37232, USA.
authors.forename: M Diana
authors.initials: MD
authors.lastname: Neely
authors.affiliation: Department of Biological Sciences, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Clayton M
authors.initials: CM
authors.lastname: Britt
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Orlando S
authors.initials: OS
authors.lastname: Hoilett
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Mechanical Engineering, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Bryson M
authors.initials: BM
authors.lastname: Brewer
authors.forename: Philip C
authors.initials: PC
authors.lastname: Samson
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McCawley
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: May
authors.affiliation: Department of Biological Sciences, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Webb
authors.affiliation: Department of Mechanical Engineering, Vanderbilt University , Nashville, Tennessee 37235, USA.
authors.forename: Deyu
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology, Vanderbilt Kennedy Center, Vanderbilt Brain Institute, Vanderbilt Center in Molecular Toxicology, Vanderbilt University , Nashville, Tennessee 37232, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bowman
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Reiserer
authors.forename: John P
authors.initials: JP
authors.lastname: Wikswo