Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215, USA.
Biomaterials. 2010 Aug;31(24):6182-9. doi: 10.1016/j.biomaterials.2010.04.041. Epub 2010 May 26.
This work examines how mechanical signals affect the barrier function and stability of engineered human microvessels in microfluidic type I collagen gels. Constructs that were exposed to chronic low flow displayed high permeabilities to bovine serum albumin and 10 kDa dextran, numerous focal leaks, low size selectivity, and short lifespan of less than one week. Higher flows promoted barrier function and increased longevity; at the highest flows, the barrier function rivaled that observed in vivo, and all vessels survived to day 14. By studying the physiology of microvessels of different geometries, we established that shear stress and transmural pressure were the dominant mechanical signals that regulated barrier function and vascular stability, respectively. In microvessels that were exposed to high flow, elevation of intracellular cyclic AMP further increased the selectivity of the barrier and strongly suppressed cell proliferation. Computational models that incorporated stress dependence successfully predicted vascular phenotype. Our results indicate that the mechanical microenvironment plays a major role in the functionality and stability of engineered human microvessels in microfluidic collagen gels.
这项工作研究了机械信号如何影响工程化人微血管在微流控 I 型胶原凝胶中的屏障功能和稳定性。暴露于慢性低流量的构建体对牛血清白蛋白和 10 kDa 葡聚糖具有高通透性、大量局灶性渗漏、低尺寸选择性以及不到一周的短寿命。较高的流量促进了屏障功能并延长了寿命；在最高流量下，屏障功能与体内观察到的相当，并且所有血管都存活到第 14 天。通过研究不同几何形状的微血管生理学，我们确定剪切应力和跨壁压分别是调节屏障功能和血管稳定性的主要机械信号。在暴露于高流量的微血管中，细胞内环腺苷酸的升高进一步提高了屏障的选择性，并强烈抑制了细胞增殖。纳入应力依赖性的计算模型成功预测了血管表型。我们的结果表明，机械微环境在微流控胶原凝胶中工程化人微血管的功能和稳定性中起着重要作用。
