ECM-mimetic heparin glycosamioglycan-functionalized surface favors constructing functional vascular smooth muscle tissue in vitro

ECM-mimetic heparin glycosamioglycan-functionalized surface favors constructing functional vascular smooth muscle tissue in vitro
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ECM模拟肝素糖胺聚糖功能化表面有利于体外构建功能性血管平滑肌组织

DOI:
10.1016/j.colsurfb.2016.06.023
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发表时间:
2016
影响因子:
5.8
通讯作者:
Zhao Qiang
Zhao Qiang
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhang Jimin;Wang Jianing;Wei Yongzhen;Gao Cheng;Chen Xuejiao;Kong Wei;Kong Deling;Zhao Qiang

文献摘要

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收缩血管平滑肌是动脉正常生理功能的重要组成部分。肝素作为一种天然的糖胺多聚糖,在促进或维持血管平滑肌细胞(VSMCs)的收缩表型方面具有重要作用。本研究通过一种简便、高效的表面改性方法制备了肝素功能化的聚己内酯(ε)非织造布,实现了肝素表面密度的大范围控制。表面肝素化显著提高了PCL的亲水性,降低了血小板的粘附性。四甲基偶氮唑盐比色法显示肝素功能化的PCL表面VSMC增殖受到明显抑制,且呈剂量依赖关系。基因分析证实,表面肝素化也促进了VSMCs从合成表型向收缩表型的转变。此外,在适当的肝素表面密度下,它允许VSMCs以一定的速度生长,同时表现出收缩的表型。VSMCs在改良的中等肝素密度的PCL垫(PCL-Hep-20)上培养2天,可形成一层收缩的平滑肌细胞。这些数据表明,肝素修饰的PCL支架可能是一种很有前途的体外培养功能性血管组织的候选材料。
Contractile vascular smooth muscle accounts for the normal physiological function of artery. Heparin, as a native glycosaminoglycan, has been well known for its important function in promoting or maintaining the contractile phenotype of vascular smooth muscle cells (VSMCs). In this study, heparin-functionalized non-woven poly(ε-caprolactone) (PCL) mat was fabricated by a facile and efficient surface modification protocol, which enables the control of surface heparin density within a broad range. Surface heparization remarkably increased the hydrophilicity of PCL, and reduced platelet adhesion. MTT assay showed that VSMC proliferation was evidently inhibited on the heparin-functionalized PCL surface in a dose-dependent manner. Gene analysis confirmed that surface heparization also promoted the transition of VSMCs from synthetic phenotype to contractile one. Furthermore, with a proper surface density of heparin, it allowed VSMCs to grow in a certain rate, while exhibiting contractile phenotype. Culture of VSMCs on a modified PCL mat with moderate heparin density (PCL-Hep-20) for 2 days resulted in a confluent layer of contractile smooth muscle cells. These data suggest that the heparin-modified PCL scaffolds may be a promising candidate to generate functional vascular tissuesin vitro.