The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts.

The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts.
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肝素改性 ePTFE 血管移植物的血液和血管细胞相容性。

DOI:
10.1016/j.biomaterials.2012.09.046
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发表时间:
2013-01
期刊:
影响因子:
14
通讯作者:
Ameer, Guillermo
Ameer, Guillermo
中科院分区:
工程技术1区
文献类型:
--
作者:
Hoshi, Ryan A.;Van Lith, Robert;Jen, Michele C.;Allen, Josephine B.;Lapidos, Karen A.;Ameer, Guillermo

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人工血管移植物不能模拟天然血管的抗血栓形成特性,因此具有较高的血栓形成和再狭窄并发症发生率。我们开发了一种将生物活性肝素(一种有效的抗凝剂糖胺聚糖)移植到ePTFE血管移植物内腔的方法,以改善其与血液和血管细胞的相互作用。肝素通过其羧基官能团与胺化聚(1,8-辛二醇-共-柠檬酸盐)(POC)结合到POC改性的ePTFE移植物上。通过血小板粘附和凝血试验对POC固定化肝素(POC-肝素)的生物活性和稳定性进行了表征。还研究了POC-肝素对原代内皮细胞(EC)、从人外周血分离的内皮祖细胞(EPCs)获得的血液生长内皮细胞(BOECs)和平滑肌细胞的粘附、活力和表型的影响。POC-肝素移植物在体外生理相关条件下保持生物活性至少一个月。具体而言,POC-肝素涂层ePTFE移植物显著降低血小板粘附并抑制全血凝血动力学。POC-肝素支持EC和BOEC粘附、活力、增殖、NO产生以及内皮细胞特异性标志物血管性血友病因子(vWF)和血管内皮钙粘蛋白(VE-钙粘蛋白)的表达。在POC-肝素上培养的平滑肌细胞显示α-肌动蛋白表达增加和细胞增殖降低。这种方法可以容易地适用于修改其他血液接触装置,如支架,其中抗血栓形成性和改善的内皮化是期望的特性。
Prosthetic vascular grafts do not mimic the antithrombogenic properties of native blood vessels and therefore have higher rates of complications that involve thrombosis and restenosis. We developed an approach for grafting bioactive heparin, a potent anticoagulant glycosaminoglycan, to the lumen of ePTFE vascular grafts to improve their interactions with blood and vascular cells. Heparin was bound to aminated poly(1,8-octanediol-co-citrate) (POC) via its carboxyl functional groups onto POC-modified ePTFE grafts. The bioactivity and stability of the POC-immobilized heparin (POC–Heparin) were characterized via platelet adhesion and clotting assays. The effects of POC–Heparin on the adhesion, viability and phenotype of primary endothelial cells (EC), blood outgrowth endothelial cells (BOECs) obtained from endothelial progenitor cells (EPCs) isolated from human peripheral blood, and smooth muscle cells were also investigated. POC–Heparin grafts maintained bioactivity under physiologically relevant conditions in vitro for at least one month. Specifically, POC–Heparin-coated ePTFE grafts significantly reduced platelet adhesion and inhibited whole blood clotting kinetics. POC–Heparin supported EC and BOEC adhesion, viability, proliferation, NO production, and expression of endothelial cell-specific markers von Willebrand factor (vWF) and vascular endothelial-cadherin (VE-cadherin). Smooth muscle cells cultured on POC–Heparin showed increased expression of α-actin and decreased cell proliferation. This approach can be easily adapted to modify other blood contacting devices such as stents where antithrombogenicity and improved endothelialization are desirable properties.
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