Thromboresistant and endothelialization effects of dopamine-mediated heparin coating on a stent material surface
Thromboresistant and endothelialization effects of dopamine-mediated heparin coating on a stent material surface
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DOI：
10.1007/s10856-012-4587-5
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发表时间：
2012-05-01
影响因子：
3.7
通讯作者：
Jeong, Myung Ho
中科院分区：
文献类型：
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作者：
Bae, In-Ho;Park, In-Kyu;Jeong, Myung Ho
表面肝素化已被证明是预防血栓形成的成功策略。受贻贝中粘附蛋白质组成的启发，作者使用多巴胺将肝素固定在支架表面。本研究旨在评估支架材料表面多巴胺介导的肝素（HPM）涂层的抗血栓和内皮化作用。通过化学键合多巴胺和肝素合成HPM。首先将钴铬（Co-Cr）合金圆盘置于HPM溶液中并应用于表面稳定性，然后进行抗血栓试验和人脐静脉内皮细胞（HUVEC）细胞毒性试验。甲苯胺蓝法和凝血酶活化法检测结果表明，肝素不仅具有抗血栓活性，而且在体外对人脐静脉内皮细胞的增殖有明显的促进作用。动物研究表明，与裸金属支架（BMS）相比，HPM涂层支架无明显的炎症反应，再狭窄率增加，表明其具有良好的生物相容性以及体内应用的安全性。此外，改善内皮细胞（EC）增殖导致更高的支柱覆盖率（即，与BMS组相比，HPM涂层支架组中具有梭形EC的内皮化）。这些结果表明，这种简单的涂层方法可以显著促进内皮化，并提供比BMS更大的安全性，因为其具有更好的抗血栓性。此外，它可以提供用于缀合二级药物如抗增殖药物的平台。
Heparinization of surfaces has proven a successful strategy to prevent thrombus formation. Inspired by the composition of adhesive proteins in mussels, the authors used dopamine to immobilize heparin on a stent surface. This study aimed to assess the thromboresistant and endothelialization effects of dopamine-mediated heparin (HPM) coating on a stent material surface. The HPM was synthesized by bonding dopamine and heparin chemically. Cobalt-chromium (Co-Cr) alloy disks were first placed in the HPM solution and applied to surface stability then underwent thromboresistant tests and human umbilical vein endothelial cells (HUVEC) cytotoxicity assays. The results showed not only thromboresistant activity and a stable state of heparin on the surfaces after investigation with toluidine blue and thrombin activation assay but also proliferation of HUVEC in vitro. Studies on animals showed that the HPM-coated stent has no obvious inflammation response and increasing of restenosis rate compared to the bare metal stent (BMS) indicating good biocompatibility as well as safety in its in vivo application. Moreover, improving the endothelial cell (EC) proliferation resulted in a higher strut-covering rate (i.e., endothelialization) with shuttle-shaped EC in the HPM-coated stent group compared to that of the BMS group. These results suggest that this facile coating approach could significantly promote endothelialization and offer greater safety than the BMS for its much improved thromboresistant property. Moreover, it may offer a platform for conjugating secondary drugs such as anti-proliferative drugs.