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Fabrication and Optimization of a Polycaprolactone-Based Ductular Blood-Brain Barrier Model Using an Electrospinning
Malak El Tfayli1, George Deeb1, Kawthar Abla2
1Biomedical Engineering Program, Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107-2020, Lebanon.
Researchers developed a novel 3D biomimetic model using a polycaprolactone scaffold that closely mimics blood-brain barrier (BBB) capillaries. This advanced in vitro model enhances understanding of CNS disorders and facilitates new drug delivery strategies.
Area of Science:
- Biomaterials Engineering
- Neuroscience
- Drug Delivery Systems
Background:
- Central nervous system (CNS) disorders represent a significant global health burden.
- Limited novel therapies exist for CNS disorders due to a lack of effective in vitro blood-brain barrier (BBB) models.
- Current models fail to accurately replicate the in vivo properties of brain capillaries, hindering therapeutic development.
Purpose of the Study:
- To develop and characterize a novel three-dimensional (3D) biomimetic scaffold for an in vitro blood-brain barrier (BBB) model.
- To assess the ability of endothelial cells to grow and form a functional barrier within the scaffold.
- To evaluate the barrier integrity and mechanical properties of the developed BBB model for CNS drug discovery.
Main Methods:
- Fabrication of a polycaprolactone (PCL) ductular scaffold using electrospinning.
- Optimization and characterization of scaffold fiber structure and mechanical strength (Young's modulus).
- Seeding of endothelial cells (ECV-304) within the scaffold, followed by barrier integrity assessment using immunofluorescence (ZO-1) and transepithelial/transendothelial electrical resistance (TEER) measurements.
Main Results:
- The optimized PCL scaffold exhibited robust mechanical strength (Young's modulus: 34.7 ± 3.59 MPa).
- Endothelial cells achieved high surface coverage (85.36 ± 14.36%) within 14 days, with high-density seeding accelerating coverage.
- The 3D model demonstrated significantly enhanced barrier function (higher ZO-1 expression and TEER values) compared to 2D controls.
Conclusions:
- A biomimetic 3D scaffold closely mimicking blood-brain capillaries was successfully developed.
- The model supports endothelial cell growth and forms a functional barrier with improved integrity.
- This advanced in vitro BBB model holds promise for studying CNS disorders and advancing drug delivery research.
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