Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA.
J Biomed Mater Res A. 2012 Jul;100(7):1815-22. doi: 10.1002/jbm.a.34137. Epub 2012 Apr 4.
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.
血浆代用品，如葡聚糖和羟乙基淀粉（HES），是旨在维持临床血管容量和移植前保存器官的溶液的重要组成部分。在这里，我们表明这些聚合物也对微流控型 I 型胶原蛋白和纤维蛋白支架中的工程微血管发挥稳定作用。标准生长培养基不含葡聚糖或 HES，导致严重的渗漏、血管塌陷和灌注灾难性失败。值得注意的是，提供 3%葡聚糖或 5%HES 的血管只有少数焦点渗漏，保持与支架的粘附，并且通常在至少 2 周内保持存活和通畅。我们发现，在存在血浆代用品的情况下，连接标记物 VE-cadherin 定位于一个宽带，但仅在也稳定血管的浓度下。结合之前的计算模型（Wong 等人，Biomaterials 2010；31:4706-4714），我们的结果表明，血浆代用品通过增强 VE-cadherin 在连接处的定位从而限制血管通透性的物理机制稳定微血管。
