A modular approach to create a neurovascular unit-on-a-chip.

Area of Science:

• Neuroscience
• Biomedical Engineering
• Cell Biology

Background:

• The neurovascular unit (NVU) is critical for brain function, but its complexity hinders disease modeling.
• Existing models often fail to replicate the intricate interactions within the NVU.

Purpose of the Study:

• To fabricate and validate a modular microsystem that mimics the human NVU.
• To establish a platform for studying neuroinflammation and screening central nervous system (CNS) therapeutics.

Main Methods:

• A multi-layered microdevice with separate neural and vascular chambers separated by a microporous membrane.
• Co-culture of neurons, astrocytes, microglia, and brain microvascular endothelial cells (RBE4).
• Assessment of cellular viability, neural activity, endothelial barrier function, and inflammatory responses.

Main Results:

• High cellular viability (>90%) in both neural and vascular compartments.
• Functional neural activity (inhibitory and excitatory potentials) and intact endothelial barrier function (dil-a-LDL uptake, vWF, ZO-1 expression, reduced dextran leakage).
• Significant activation of microglia and astrocytes in response to vascular TNF-α stimulation, mimicking neuroinflammation.

Conclusions:

• The developed microsystem successfully recapitulates key functions of the NVU.
• This biomimetic platform serves as a valuable tool for mechanistic studies of neurodegenerative disorders.
• The platform shows potential for screening CNS therapeutics in toxicology and neuroinfectious diseases.