Dept. of Mechanical Engineering, MIT, Cambridge, MA, USA.
Dept. of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy.
Biomaterials. 2022 Jan;280:121248. doi: 10.1016/j.biomaterials.2021.121248. Epub 2021 Nov 13.
Hemodynamics play a central role in the health and disease of the coronary and peripheral vascular systems. Vessel-lining endothelial cells are known mechanosensors, responding to disturbances in flow - with mechanosensitivity hypothesized to change in response to metabolic demands. The health of our smallest microvessels have been lauded as a prognostic marker for cardiovascular health. Yet, despite numerous animal models, studying these small vessels has proved difficult. Microfluidic technologies have allowed a number of 3D vascular models to be developed and used to investigate human vessels. Here, two such systems are employed for examining 1) interstitial flow effects on neo-vessel formation, and 2) the effects of flow-conditioning on vascular remodeling following sustained static culture. Interstitial flow is shown to enhance early vessel formation via significant remodeling of vessels and interconnected tight junctions of the endothelium. In formed vessels, continuous flow maintains a stable vascular diameter and causes significant remodeling, contrasting the continued anti-angiogenic decline of statically cultured vessels. This study is the first to couple complex 3D computational flow distributions and microvessel remodeling from microvessels grown on-chip (exposed to flow or no-flow conditions). Flow-conditioned vessels (WSS < 1Pa for 30 μm vessels) increase endothelial barrier function, result in significant changes in gene expression and reduce reactive oxygen species and anti-angiogenic cytokines. Taken together, these results demonstrate microvessel mechanosensitivity to flow-conditioning, which limits deleterious vessel regression in vitro, and could have implications for future modeling of reperfusion/no-flow conditions.
血流动力学在冠状动脉和外周血管系统的健康和疾病中起着核心作用。血管内皮细胞是已知的机械感受器，对血流紊乱做出反应——机械敏感性被假设为响应代谢需求而改变。我们最小的微血管的健康一直被誉为心血管健康的预后标志物。然而，尽管有许多动物模型，研究这些小血管仍然很困难。微流控技术已经允许许多 3D 血管模型的发展，并用于研究人类血管。在这里，使用了两种这样的系统来研究 1）间质流对新血管形成的影响，以及 2）持续静态培养后对血管重塑的流动调节作用。间质流通过显著重塑血管和内皮细胞的紧密连接，显示出增强早期血管形成的作用。在形成的血管中，连续流动保持血管直径的稳定，并导致显著的重塑，与静态培养的血管持续抗血管生成下降形成对比。这项研究首次将复杂的 3D 计算血流分布与在芯片上生长的微脉管（暴露于流动或无流动条件下）的微脉管重塑相结合。经过流动调节的血管（对于 30μm 的血管，WSS <1Pa）增加了内皮屏障功能，导致基因表达发生显著变化，并减少了活性氧物质和抗血管生成细胞因子。总之，这些结果表明微脉管对流动调节的机械敏感性，可以限制体外有害血管退化，并可能对再灌注/无流动条件的未来建模产生影响。
