Barrier-on-a-chip device enables study of brain disease

The Wyss Institute has developed a human blood-brain barrier-on-a-chip device that offers new ways of studying drug delivery and neurological disease in vitro

The blood-brain barrier at the interface between the brain's blood vessels and nerve cells acts as a vital gatekeeper to the brain, allowing essential nutrients and fluids to pass into the central nervous system and the brain's neurons while keeping out harmful toxins and bacterial infection.

Yet this barrier can also block the delivery of therapies for treating neurological diseases or brain injury.

A team at the Wyss Institute for Biologically Inspired Engineering, led by Wyss Institute Founding Director Donald Ingber, has developed a method for modeling the 3D structure of the human blood-brain barrier inside a microfluidic device, which will help scientists study human neurovascular function and inflammation in vitro.

Anna Herland, a postdoctoral fellow at the Wyss Institute and the first author on the new study, said: "It's very difficult to get small molecule drugs and biologics into the brain due to the blood-brain barrier, and until now there hasn't been a good in vitro model for studying the multi-cellular interactions that govern the barrier's permeability in humans."

To develop their 3D blood-brain barrier on-a-chip, the team used a microengineering technique to fabricate a hollow blood vessel lined by human endothelial cells surrounded by an extracellular matrix containing human pericytes and astrocytes that together form the blood-brain barrier within the microvessels of brains.

They did so by forming a microchannel inside a clear, polymer chip, filling the channel with collagen matrix containing human brain astrocyte cells, and then forming a long narrow lumen from one end to the other using a ‘viscous fingering’ method.

The resulting lumen, representing the shape of a blood vessel, was then seeded with human brain pericyte cells and, finally, lined with living human endothelial cells that normally build the interior surfaces of vessel walls.

The cells, nourished by nutrients and a blood substitute flowing through the vessel-like microchannel, reconstituted a blood-brain barrier to small molecules similar to that seen in vivo.

Using this model, the Wyss team studied neuroinflammatory response in vitro by introducing a pro-inflammatory protein that is associated with several diseases of the central nervous system including Alzheimer's, stroke, brain ischemia, multiple sclerosis, traumatic brain injury, and others.