A bioengineered array of 3D microvessels for vascular permeability assay.

Blood vessels exhibit highly regulated barrier function allowing selective passage of macromolecules. Abnormal vascular permeability caused by disorder in barrier function is often associated with various pathological states such as tumor progression or pulmonary fibrosis. There are no realistic in vitro models for measuring vascular permeability as most models are limited to mimicking anatomical structural properties of in vivo vessel barriers. This paper presents a reliable microfluidic-based chip for measuring permeability by engineering tubular perfusable microvessels. This platform is compatible with high resolution, live-cell time-lapse imaging and high throughput permeability measurements. The microvessels were formed by natural angiogenic process and thus exhibit reliable barrier properties with permeability coefficient of 1.55×10(-6)cm/s (for 70kDa FITC-dextran). The bioengineered microvessels showed properties similar to in vivo vessels in terms of cell-cell junction expression (ZO-1, Claudin-5 and VE-cadherin) and response to agonists such as histamine and TNF-α. We showed that hyperpermeability of the tumor microvessel could be normalized with anti-VEGF (bevacizumab) treatment, consistent with the mechanism of action for bevacizumab. The method developed here provides a relatively simple, robust technique for assessing drug effects on permeability of microvessels with a number of potential applications in fundamental vascular biology as well as drug screening.