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Microfluidic organ-on-chip technology for blood-brain barrier research.

van der Helm MW, van der Meer AD, Eijkel JC, van den Berg A, Segerink LI - Tissue Barriers (2016)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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 e3ndothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function. 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.

No MeSH data available.


Flow profiles inside the BBB chip of Prabhakarpandian42 (A) and Booth35 (B) and at different aspect ratios (C), modeled with MATLAB R2013a. The endothelial cells are cultured on the bottom surface of the depicted channel.
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f0003: Flow profiles inside the BBB chip of Prabhakarpandian42 (A) and Booth35 (B) and at different aspect ratios (C), modeled with MATLAB R2013a. The endothelial cells are cultured on the bottom surface of the depicted channel.

Mentions: In a tube with a circular cross-section the wall shear stress will be equal along the entire inner wall because of the cylindrical symmetry. However, inside a rectangular channel the shear stress will not be uniform across the channel width because of the presence of the side walls. Therefore, to achieve a mostly uniform shear stress on all cells across the channel width, the width should be much higher than the height (), resulting in a flat flow profile. This situation is illustrated in FigureĀ 3 for different aspect ratios (channel height over channel width). The flow profile in a channel with a rectangular cross-section can be approximated with the following equations:Figure 3.


Microfluidic organ-on-chip technology for blood-brain barrier research.

van der Helm MW, van der Meer AD, Eijkel JC, van den Berg A, Segerink LI - Tissue Barriers (2016)

Flow profiles inside the BBB chip of Prabhakarpandian42 (A) and Booth35 (B) and at different aspect ratios (C), modeled with MATLAB R2013a. The endothelial cells are cultured on the bottom surface of the depicted channel.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836466&req=5

f0003: Flow profiles inside the BBB chip of Prabhakarpandian42 (A) and Booth35 (B) and at different aspect ratios (C), modeled with MATLAB R2013a. The endothelial cells are cultured on the bottom surface of the depicted channel.
Mentions: In a tube with a circular cross-section the wall shear stress will be equal along the entire inner wall because of the cylindrical symmetry. However, inside a rectangular channel the shear stress will not be uniform across the channel width because of the presence of the side walls. Therefore, to achieve a mostly uniform shear stress on all cells across the channel width, the width should be much higher than the height (), resulting in a flat flow profile. This situation is illustrated in FigureĀ 3 for different aspect ratios (channel height over channel width). The flow profile in a channel with a rectangular cross-section can be approximated with the following equations:Figure 3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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 e3ndothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function. 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.

No MeSH data available.