title: Microfluidic organ-on-chip technology for blood-brain barrier research.
abstract: Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized endothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function [corrected]. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.
authors.affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.
authors.forename: Marinke W
authors.initials: MW
authors.lastname: van der Helm
authors.affiliation: Applied Stem Cell Technologies, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente ; Enschede, The Netherlands.
authors.forename: Andries D
authors.initials: AD
authors.lastname: van der Meer
authors.affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.
authors.forename: Jan C T
authors.initials: JC
authors.lastname: Eijkel
authors.affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.
authors.forename: Loes I
authors.initials: LI
authors.lastname: Segerink
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D046208:Microchip Analytical Procedures / Q000379:methods*; D044085:Microfluidics / Q000379:methods*
keywords: BBBs-on-chips; blood-brain barrier; endothelial cells; microfabrication; microfluidics; organs-on-chips