Impact of cyclic stretch on induced elastogenesis within collagenous conduits.
Impact of cyclic stretch on induced elastogenesis within collagenous conduits.
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DOI：
10.1089/ten.tea.2013.0294
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发表时间：
2014-02
影响因子：
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通讯作者：
L. Venkataraman;C. Bashur;A. Ramamurthi
中科院分区：
文献类型：
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作者：
L. Venkataraman;C. Bashur;A. Ramamurthi
血管管道的体外组织工程需要几种外部因素之间的协同作用，包括生化补充和机械传导刺激。本研究的目的是改善成人血管平滑肌细胞的方向和弹性基质合成内的三维管状胶原凝胶结构。我们使用了先前在我们实验室中测试的弹性因子（EF）的组合，沿着低振幅（2.5%）的循环周向应变，以一系列频率（0.5、1.5和3 Hz）输送。培养21天后，分析构建体的弹性基质结果、基质金属蛋白酶（MMPs）-2和-9的活性、细胞密度和表型以及构建体的机械性质。虽然细胞密度不受拉伸的影响，但相对于对照，所有拉伸构建体中的收缩表型标记物均升高。用在1.5Hz拉伸的EFs培养的构建体表现出最大的弹性蛋白mRNA表达和总基质弹性蛋白（相对于静态EFs对照超过六倍）。MMP-2含量在所有处理条件下相当，但MMP-9水平在较高频率（1.5和3 Hz）下升高。实现了最小的周向取向，并且在处理条件之间的机械性能保持相当。总体而言，用EF处理并以1.5 Hz拉伸的结构表现出最大的弹性结果。
In vitro tissue engineering of vascular conduits requires a synergy between several external factors, including biochemical supplementation and mechanotranductive stimulation. The goal of this study was to improve adult human vascular smooth muscle cell orientation and elastic matrix synthesis within 3D tubular collagen gel constructs. We used a combination of elastogenic factors (EFs) previously tested in our lab, along with cyclic circumferential strains at low amplitude (2.5%) delivered at a range of frequencies (0.5, 1.5, and 3 Hz). After 21 days of culture, the constructs were analyzed for elastic matrix outcomes, activity of matrix metalloproteinases (MMPs)-2 and -9, cell densities and phenotype, and mechanical properties of constructs. While cell densities remained unaffected by the addition of stretch, contractile phenotypic markers were elevated in all stretched constructs relative to control. Constructs cultured with EFs stretched at 1.5 Hz exhibited the maximum elastin mRNA expression and total matrix elastin (over sixfold vs. the static EFs control). MMP-2 content was comparable in all treatment conditions, but MMP-9 levels were elevated at the higher frequencies (1.5 and 3 Hz). Minimal circumferential orientation was achieved and the mechanical properties remained comparable among the treatment conditions. Overall, constructs treated with EFs and stretched at 1.5 Hz exhibited the most elastogenic outcomes.