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A pump‐free tricellular blood–brain barrier on‐a‐chip model to understand barrier property and evaluate drug response
Author(s) -
Yu Fang,
Kumar Nivasini DO Selva,
Foo Lynette C.,
Ng Sum Huan,
Hunziker Walter,
Choudhury Deepak
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27260
Subject(s) - blood–brain barrier , tight junction , drug delivery to the brain , in vivo , chemistry , microbiology and biotechnology , neuroscience , biology , central nervous system
Disruption of the blood–brain barrier (BBB) leads to various neurovascular diseases. Development of therapeutics required to cross the BBB is difficult due to a lack of relevant in vitro models. We have developed a three‐dimensional (3D) microfluidic BBB chip (BBBC) to study cell interactions in the brain microvasculature and to test drug candidates of neurovascular diseases. We isolated primary brain microvascular endothelial cells (ECs), pericytes, and astrocytes from neonatal rats and cocultured them in the BBBC. To mimic the 3D in vivo BBB structure, we used type I collagen hydrogel to pattern the microchannel via viscous finger patterning technique to create a matrix. ECs, astrocytes, and pericytes were cocultured in the collagen matrix. The fluid flow in the BBBC was controlled by a pump‐free strategy utilizing gravity as driving force and resistance in a paper‐based flow resistor. The primary cells cultured in the BBBC expressed high levels of junction proteins and formed a tight endothelial barrier layer. Addition of tumor necrosis factor alpha to recapitulate neuroinflammatory conditions compromised the BBB functionality. To mitigate the neuroinflammatory stimulus, we treated the BBB model with the glucocorticoid drug dexamethasone, and observed protection of the BBB. This BBBC represents a new simple, cost‐effective, and scalable in vitro platform for validating therapeutic drugs targeting neuroinflammatory conditions.