Abstract
The blood-brain barrier (BBB) is a critical physical and chemical barrier that maintains brain homeostasis. Researchers in academia and industry are highly motivated to develop experimental models that can accurately mimic the physiological characteristics of the BBB. Microfluidic systems, which manipulate fluids at the micrometer scale, are ideal tools for simulating the BBB microenvironment. In this review, we summarized the progress in the design and evaluation of microfluidic in vitro BBB models, including advances in chip materials, porous membranes, the use of endothelial cells, the importance of shear stress, the detection specific markers to monitor tight junction formation and integrity, measurements of TEER and permeability. We also pointed out several shortcomings of the current microfluidic models. The purpose of this paper is to let the readers understand the characteristics of different types of model design, and select appropriate design parameters according to the research needs, so as to obtain the best experimental results. We believe that the microfluidics BBB models will play an important role in neuroscience and pharmaceutical research.
Highlights
The blood-brain barrier (BBB) is a highly selective barrier that regulates passive and active transport between the brain parenchyma and peripheral blood [1,2]
The BBB is a complex dynamic physiological structure network, the molecular basis that underlie BBB function depend on close interactions between adjacent brain microvascular endothelial cells (BMECs)
As the interface between the blood and the central nervous system (CNS), the BBB is critical for maintaining a steady state environment in the CNS
Summary
The blood-brain barrier (BBB) is a highly selective barrier that regulates passive and active transport between the brain parenchyma and peripheral blood [1,2]. The BBB is a complex dynamic physiological structure network, the molecular basis that underlie BBB function depend on close interactions between adjacent brain microvascular endothelial cells (BMECs). These cells form a layer that is tightly sealed by a junctional complex composed of tight junctions and adherens junctions [5,6]. Tight junctions, which play an essential role in maintaining BBB integrity, are structures formed by at least three different types of transmembrane proteins, such as occludin, claudin and junctional adhesive molecule [7,8]. Disruption or dysfunction of the BBB has been linked to a wide range of neurological disorders, including brain tumors, epilepsy, ischemic stroke, Alzheimer’s disease, and multiple sclerosis [13,14,15,16,17]
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