Biology and Models of the Blood-Brain Barrier Hajal, Cynthia; Le Roi, Baptiste; Kamm, Roger D ...
Annual review of biomedical engineering,
07/2021, Volume:
23, Issue:
1
Journal Article
Peer reviewed
Open access
The blood-brain barrier (BBB) is one of the most selective endothelial barriers. An understanding of its cellular, morphological, and biological properties in health and disease is necessary to ...develop therapeutics that can be transported from blood to brain. In vivo models have provided some insight into these features and transport mechanisms adopted at the brain, yet they have failed as a robust platform for the translation of results into clinical outcomes. In this article, we provide a general overview of major BBB features and describe various models that have been designed to replicate this barrier and neurological pathologies linked with the BBB. We propose several key parameters and design characteristics that can be employed to engineer physiologically relevant models of the blood-brain interface and highlight the need for a consensus in the measurement of fundamental properties of this barrier.
Organ-on-a-Chip platforms provide rich opportunities to observe interactions between
different cell types under in vivo-like conditions, i.e., in the presence
of flow. Yet, the costs and know-how ...required for the fabrication and implementation of
these platforms restrict their accessibility. This study introduces and demonstrates a
novel Insert-Chip: a microfluidic device that provides the functionality of an
Organ-on-a-Chip platform, namely, the capacity to co-culture cells, expose them to flow,
and observe their interactions—yet can easily be integrated into standard culture systems
(e.g., well plates or multi-electrode arrays). The device is produced using
stereolithograpy 3D printing and is user-friendly and reusable. Moreover, its design
features overcome some of the measurement and imaging challenges characterizing standard
Organ-on-a-Chip platforms. We have co-cultured endothelial and epithelial cells under flow
conditions to demonstrate the functionality of the device. Overall, this novel
microfluidic device is a promising platform for the investigation of biological functions,
cell–cell interactions, and response to therapeutics.
Despite significant advancements in in vitro cardiac modeling approaches, researchers still lack the capacity to obtain in vitro measurements of a key indicator of cardiac function: contractility, or ...stroke volume under specific loading conditions-defined as the pressures to which the heart is subjected prior to and during contraction. This work puts forward a platform that creates this capability, by providing a means of dynamically controlling loading conditions in vitro. This dynamic tissue loading platform consists of a thin magnetoresponsive hydrogel cantilever on which 2D engineered myocardial tissue is cultured. Exposing the cantilever to an external magnetic field-generated by positioning magnets at a controlled distance from the cantilever-causes the hydrogel film to stretch, creating tissue load. Next, cell contraction is induced through electrical stimulation, and the force of the contraction is recorded, by measuring the cantilever's deflection. Force-length-based measurements of contractility are then derived, comparable to clinical measurements. In an illustrative application, the platform is used to measure contractility both in untreated myocardial tissue and in tissue exposed to an inotropic agent. Clear differences are observed between conditions, suggesting that the proposed platform has significant potential to provide clinically relevant measurements of contractility.
Mechanical forces play critical roles in a wide variety of biological processes and diseases, yet measuring them directly at the molecular level remains one of the main challenges of mechanobiology. ...Here, we show a strategy to “Dip-conjugate” biologically derived materials at the chemical level to mechanophores, force-responsive molecular entities, using Click-chemistry. Contrary to classical prepolymerization mechanophore incorporation, this new protocol leads to detectable mechanochromic response with as low as 5% strain, finally making mechanophores relevant for many biological processes that have previously been inaccessible. Our results demonstrate the ubiquity of the technique with activation in synthetic polymers, carbohydrates, and proteins under mechanical force, with alpaca wool fibers as a key example. These results push the limits for mechanophore use in far more types of polymeric materials in applications ranging from molecular-level force damage detection to direct and quantitative 3D force measurements in mechanobiology.
Lettre de Jean-Baptiste Colbert (contrôleur général des finances) aux commissaires du roi aux états de Languedoc datée du 25 janvier 1666, à Saint-Germain-en-Laye. In: Correspondance administrative ...sous le règne de Louis XIV, recueillie et mise en ordre par G. B. Depping. Tome I. Etats provinciaux – Affaires municipales et communales. Paris : Imprimerie nationale, 1850. p. 209.
Lettre des commissaires du roi aux états de Languedoc à Jean-Baptiste Colbert (ministre d'Etat) datée du 04 décembre 1665, à Béziers. In: Correspondance administrative sous le règne de Louis XIV, ...recueillie et mise en ordre par G. B. Depping. Tome I. Etats provinciaux – Affaires municipales et communales. Paris : Imprimerie nationale, 1850. pp. 201-202.
Lettre des commissaires du roi aux états de Languedoc à Jean-Baptiste Colbert (ministre d'Etat) datée du 15 février 1666, à Béziers. In: Correspondance administrative sous le règne de Louis XIV, ...recueillie et mise en ordre par G. B. Depping. Tome I. Etats provinciaux – Affaires municipales et communales. Paris : Imprimerie nationale, 1850. pp. 213-214.
Lettre des commissaires du roi aux états de Languedoc à Jean-Baptiste Colbert (contrôleur général des finances) datée du 11 décembre 1665, à Béziers. In: Correspondance administrative sous le règne ...de Louis XIV, recueillie et mise en ordre par G. B. Depping. Tome I. Etats provinciaux – Affaires municipales et communales. Paris : Imprimerie nationale, 1850. pp. 202-203.
Lettre des commissaires du roi aux états de Languedoc à Jean-Baptiste Colbert (contrôleur général des finances) datée du 12 décembre 1671, à Montpellier. In: Correspondance administrative sous le ...règne de Louis XIV, recueillie et mise en ordre par G. B. Depping. Tome I. Etats provinciaux – Affaires municipales et communales. Paris : Imprimerie nationale, 1850. p. 269.
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