BBB-on-a-Chip: Modeling Functional Human Blood-Brain Barrier by Mimicking 3D Brain Angiogenesis Using Microfluidic Chip.

Organ-on-a-chip enables human cell-based 3D tissue culture, which recapitulates the physiological structure and function of the tissue. In terms of the blood-brain barrier (BBB) modeling, the 3D structure of the vessel is essential for studying the cellular interactions among BBB composing cells and investigating the barrier function. Here, we describe a BBB-on-a-chip model with 3D perfusable human vasculature tri-cultured with pericytes and astrocytes. The culture method is based on mimicking angiogenic sprouting since the barrier formation is parallel with angiogenesis during the developmental process. This microfluidic-based 3D tri-culture system enables the comparative study on how surrounding BBB-related cells affect brain angiogenic sprouting. Moreover, the engineered perfusable vasculature is eligible for quantitative analysis on barrier function such as efflux transport system. We expect the BBB-on-a-chip could be used to enhance understanding BBB-related pathologies as well as the drug modulating barrier function of BBB.