BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function.

Area of Science:

• Neuroscience
• Biomedical Engineering
• Cell Biology

Background:

• The blood-brain barrier (BBB) protects the brain but its dysfunction is implicated in neurodegenerative diseases.
• Understanding BBB breakdown mechanisms is crucial for developing effective treatments.
• Existing models often lack the complexity to fully replicate in vivo BBB conditions.

Purpose of the Study:

• To develop a novel, miniaturized, and realistic in vitro model of the human blood-brain barrier.
• To investigate the mechanical and biochemical modulation of BBB function.
• To provide a platform for studying drug passage and neurodegenerative disease mechanisms.

Main Methods:

• Utilized a microfluidic chip with the immortalized human brain endothelial cell line hCMEC/D3.
• Integrated electrodes for measuring transendothelial electrical resistance (TEER) to assess barrier tightness.
• Applied fluid shear stress and tumor necrosis factor alpha (TNF-α) stimulation to modulate barrier function.

Main Results:

• hCMEC/D3 cells cultured on-chip maintained barrier integrity for up to 7 days, showing comparable TEER values to Transwell assays.
• Shear stress significantly enhanced barrier tightness, increasing TEER by threefold.
• TNF-α stimulation disrupted the barrier, decreasing TEER tenfold.
• Expression of the tight junction protein Zonula Occludens-1 (ZO-1) was confirmed.

Conclusions:

• The developed microfluidic BBB model is a realistic and sensitive platform for studying barrier function.
• This model allows for detailed investigation of BBB dynamics under mechanical and inflammatory stimuli.
• It holds potential for evaluating drug efficacy and advancing neurodegenerative disease research.