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用于调节人冠状动脉细胞表型和氧化反应的模块化聚合物设计,用于潜在的支架涂层应用。

Modular polymer design to regulate phenotype and oxidative response of human coronary artery cells for potential stent coating applications.

机构信息

Department of Biomedical Engineering, Vanderbilt University, VU Station B 351631, 5824 Stevenson Center, Nashville, TN 37235, USA.

出版信息

Acta Biomater. 2012 Feb;8(2):559-69. doi: 10.1016/j.actbio.2011.10.003. Epub 2011 Oct 8.

Abstract

Polymer properties can be tailored by copolymerizing subunits with specific physico-chemical characteristics. Vascular stent materials require biocompatibility, mechanical strength, and prevention of restenosis. Here we copolymerized poly(ε-caprolactone) (PCL), poly(ethylene glycol) (PEG), and carboxyl-PCL (cPCL) at varying molar ratios and characterized the resulting material properties. We then performed a short-term evaluation of these polymers for their applicability as potential coronary stent coating materials with two primary human coronary artery cell types: smooth muscle cells (HCASMC) and endothelial cells (HCAEC). Changes in proliferation and phenotype were dependent upon intracellular reactive oxygen species (ROS) levels, and 4%PEG-96%PCL-0%cPCL was identified as the most appropriate coating material for this application. After 3days on this substrate HCASMC maintained a healthy contractile phenotype and HCAEC exhibited a physiologically relevant proliferation rate and a balanced redox state. Other test substrates promoted a pathological, synthetic phenotype of HCASMC and/or hyperproliferation of HCAEC. Phenotypic changes of HCASMC appeared to be modulated by the Young's modulus and surface charge of the test substrates, indicating a structure-function relationship that can be exploited for intricate control over vascular cell functions. These data indicate that tailored copolymer properties can direct vascular cell behavior and provide insights for further development of biologically instructive stent coating materials.

摘要

聚合物的性能可以通过共聚具有特定物理化学特性的亚单位来进行调整。血管支架材料需要具有生物相容性、机械强度和防止再狭窄的特性。在这里,我们共聚了聚(ε-己内酯)(PCL)、聚乙二醇(PEG)和羧基-PCL(cPCL),并改变了它们的摩尔比,对得到的材料性能进行了表征。然后,我们使用两种主要的人冠状动脉细胞类型:平滑肌细胞(HCASMC)和内皮细胞(HCAEC),对这些聚合物作为潜在冠状动脉支架涂层材料的适用性进行了短期评估。细胞增殖和表型的变化取决于细胞内的活性氧(ROS)水平,4%PEG-96%PCL-0%cPCL 被确定为最适合这种应用的涂层材料。在这种基质上培养 3 天后,HCASMC 保持了健康的收缩表型,HCAEC 表现出了生理相关的增殖率和平衡的氧化还原状态。其他测试基质促进了 HCASMC 的病理性、合成表型和/或 HCAEC 的过度增殖。HCASMC 的表型变化似乎受到测试基质的杨氏模量和表面电荷的调节,这表明存在一种结构-功能关系,可以用于对血管细胞功能进行复杂的控制。这些数据表明,定制化的共聚物特性可以指导血管细胞的行为,并为进一步开发具有生物指导意义的支架涂层材料提供了思路。

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本文引用的文献

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Reactive oxygen species signaling in vascular smooth muscle cells.血管平滑肌细胞中的活性氧信号传导
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