Plasma expanders stabilize human microvessels in microfluidic scaffolds.

Abstract

Plasma expanders such as dextran and hydroxyethyl starch (HES) are important components of solutions designed to maintain vascular volume in the clinical setting and to preserve organs ex vivo before transplantation. Here, we show that these polymers also exert stabilizing effects on engineered microvessels in microfluidic type I collagen and fibrin scaffolds. Standard growth media, which did not contain dextran or HES, led to severe leakage, vascular collapse, and catastrophic failure of perfusion. Remarkably, vessels that were provided with 3% dextran or 5% HES had few focal leaks, maintained adhesion to the scaffold, and were typically viable and patent for at least 2 weeks. We found that the junctional marker VE-cadherin localized to a wide band in the presence of plasma expanders, but only at concentrations that also stabilized vessels. In conjunction with a previous computational model (Wong et al., Biomaterials 2010;31:4706-4714), our results suggest that plasma expanders stabilize microvessels via physical mechanisms that enhance VE-cadherin localization at junctions and thereby limit vascular leakiness.