RT Journal Article
SR 00
ID 10.1002/adhm.202303777
A1 Schofield, Christina
A1 Sarrigiannidis, Stylianos
A1 Moran-Horowich, Alejandro
A1 Jackson, Emma
A1 Rodrigo-Navarro, Aleixandre
A1 Van Agtmael, Tom
A1 Cantini, Marco
A1 Dalby, Matthew J.
A1 Salmeron-Sanchez, Manuel
T1 An in vitro model of the blood-brain barrier for the investigation and isolation of the key drivers of barriergenesis
JF Advanced Healthcare Materials
YR 2024
FD 2024-12-27
VO 13
IS 32
K1 BBB, ECM, electrospinning, growth factors, in vitro model.
AB 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.
NO 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.
PB Wiley
SN 2192-2640
LK https://eprints.gla.ac.uk/330576/