Three-Dimensional Dynamic Blood-Brain Barrier Model Incorporating Native Cell Culture Systems Based on Shape Memory...

Area of Science:

• Biomedical Engineering
• Neuroscience
• Pharmacology

Background:

• The blood-brain barrier (BBB) presents a significant challenge for drug delivery to the brain.
• Existing in vitro models often lack the complexity and dynamic nature of the in vivo BBB.

Purpose of the Study:

• To engineer a high-fidelity, three-dimensional (3D) dynamic in vitro blood-brain barrier (BBB) model.
• To characterize the barrier function and assess drug transport across the developed BBB model.

Main Methods:

• Integration of a dynamic fluid system with a 3D cell-scaffold capable of shape transformation.
• Characterization of barrier integrity using transendothelial electrical resistance and permeability assays.
• Assessment of BBB-related protein expression and polarized transport of a P-gp substrate.
• Evaluation of the transport characteristics of seven model drugs across the BBB.

Main Results:

• The model demonstrated a high transendothelial electrical resistance (523 Ω cm²) and low phenol red permeability (2.8-3.8 × 10⁻⁶ cm⁻¹s).
• Expression of key BBB proteins (VE-cadherin, Occludin, Claudin-5, ZO-1, P-gp) and polarized P-gp transport were confirmed.
• Differential transport of seven model drugs across the BBB was successfully presented.

Conclusions:

• A robust 3D dynamic BBB model with vascular-like architecture and fluid shear forces was successfully constructed.
• The model serves as a valuable platform for researching drug trafficking across the BBB.
• This model facilitates the development of novel therapeutics for brain diseases.