Navy

Improved blood-brain barrier model

Construction of simulated brain microvessels which incorporate all human-derived cellular components including brain microvascular endothelial cells, astrocytes, and pericytes during construction of the microvessels better mimics the BBB microenvironment

Medical & Biotechnology

While in vivo models are the gold standard for addressing blood-brain barrier (BBB) functionality and drug safety, they suffer from the lack of human complementarity, with an estimated 80 percent of candidate drugs successfully tested in small animals failing in human clinical trials. While such failures are not solely attributable to a lack of adequate BBB models, there is a large need for more relevant models.

The blood–brain barrier is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system. (iStock photo)

To meet this need, Navy research chemists have constructed synthetic human blood vessels using human brain-derived endothelial cells and incorporated these into a tissue model that contains astrocytes and other neurons and microglia. Multi-cell type microvessels, in this case, synthetic Human Endothelial Microvessels (HEMVs), which incorporate cells such as astrocytes and pericytes yield a highly representative BBB in vitro model with a functional lumen containing brain-derived microvascular endothelial cells and a polymer wall containing human astrocytes and pericytes.

Construction of this model leverages a microfluidic method based on sheath flow to generate hollow microvessels that can incorporate common BBB cells. This results in a superior model which eliminates the need for unreliable transwell membrane-based assays. The synthetic blood vessels include a hollow tube having a lumen and a polymer wall comprising extracellular matrix components, the tube has an outer diameter of 50 to 250 μm with living brain microvascular endothelial cells within the lumen and living astrocytes disposed within the polymer wall.

Applications for these microvessels include BBB permeability studies, drug delivery research, and brain-targeted diseases resulting from viral or bacterial infection.

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