An in vitro model of the blood-brain barrier for the investigation and isolation of the key drivers of barriergenesis
Source: https://eprints.gla.ac.uk/330576/ Parent: https://eprints.gla.ac.uk/view/project_code/315918.html
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An in vitro model of the blood-brain barrier for the investigation and isolation of the key drivers of barriergenesis
Schofield, Christina, Sarrigiannidis, Stylianos, Moran-Horowich, Alejandro, Jackson, Emma ORCID: https://orcid.org/0000-0002-7537-4141, Rodrigo-Navarro, Aleixandre ORCID: https://orcid.org/0000-0002-3786-0464, Van Agtmael, Tom ORCID: https://orcid.org/0000-0003-4282-449X, Cantini, Marco ORCID: https://orcid.org/0000-0003-0326-1508, Dalby, Matthew J. ORCID: https://orcid.org/0000-0002-0528-3359 and Salmeron-Sanchez, Manuel ORCID: https://orcid.org/0000-0002-8112-2100 (2024) An in vitro model of the blood-brain barrier for the investigation and isolation of the key drivers of barriergenesis. Advanced Healthcare Materials, 13(32), 2303777. (doi: 10.1002/adhm.202303777) (PMID:39101628) (PMCID:PMC11670300)
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Abstract
The blood–brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions.
| Item Type: | Articles |
| Additional Information: | This study was supported by EPSRC through a program grant(EP/P001114/1) and the Spanish Ministry of Science and InnovationMCIN/AEI/10.13039/501100011033 through the PID2022-136433OB-021grant M.S-S. is grateful for financial support from the European Re-search Council AdG (Devise, 101054728). IBEC is member of CERCA Pro-gramme/Generalitat de Catalunya. |
| Keywords: | BBB, ECM, electrospinning, growth factors, in vitro model. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Salmeron-Sanchez, Professor Manuel and Sarrigiannidis, Mr Stylianos and Van Agtmael, Professor Tom and Jackson, Dr Emma and Dalby, Professor Matthew and Rodrigo-Navarro, Mr Aleixandre and Cantini, Dr Marco and Schofield, Ms Christina |
| Authors: | Schofield, C., Sarrigiannidis, S., Moran-Horowich, A., Jackson, E., Rodrigo-Navarro, A., Van Agtmael, T., Cantini, M., Dalby, M. J., and Salmeron-Sanchez, M. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Science and Engineering > School of Engineering College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Journal Name: | Advanced Healthcare Materials |
| Publisher: | Wiley |
| ISSN: | 2192-2640 |
| ISSN (Online): | 2192-2659 |
| Published Online: | 05 August 2024 |
| Copyright Holders: | Copyright: © 2024 The Author(s) |
| First Published: | First published in Advanced Healthcare Materials 13(32): 2303777 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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Funder and Project Information
Funder and Project Information
Funder and Project Information
Project Code
Award No
Project Name
Principal Investigator
Funder's Name
Funder Ref
Lead Dept
Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicine
Manuel Salmeron-Sanchez
Engineering and Physical Sciences Research Council (EPSRC)
EP/P001114/1
ENG - Biomedical Engineering
DEVISE - Engineered viscoelasticity in regenerative microenvironments
Manuel Salmeron-Sanchez
101054728
ENG - Biomedical Engineering
Deposit and Record Details
| ID Code: | 330576 |
| Depositing User: | Mr Matt Mahon |
| Datestamp: | 09 Aug 2024 08:57 |
| Last Modified: | 05 Mar 2025 12:12 |
| Date of acceptance: | 25 July 2024 |
| Date of first online publication: | 5 August 2024 |
| Date Deposited: | 9 August 2024 |
| Data Availability Statement: | Yes |
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