The Heart Research Center of Chonnam National University Hospital Designated by Korea Ministry of Health and Welfare, Gwangju 501-757, Republic of Korea.
J Mater Sci Mater Med. 2012 May;23(5):1259-69. doi: 10.1007/s10856-012-4587-5. Epub 2012 Mar 3.
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.
表面肝素化已被证明是预防血栓形成的一种成功策略。受贻贝中粘合蛋白组成的启发，作者使用多巴胺将肝素固定在支架表面。本研究旨在评估多巴胺介导的肝素（HPM）涂层在支架材料表面的抗血栓形成和内皮化效果。通过化学结合多巴胺和肝素合成 HPM。首先将钴铬（Co-Cr）合金盘置于 HPM 溶液中，进行表面稳定性处理，然后进行抗血栓形成试验和人脐静脉内皮细胞（HUVEC）细胞毒性试验。结果表明，不仅在甲苯胺蓝和凝血酶激活试验后调查显示表面具有抗血栓形成活性和肝素的稳定状态，而且 HUVEC 在体外也具有增殖能力。动物研究表明，与裸金属支架（BMS）相比，HPM 涂层支架没有明显的炎症反应和再狭窄率增加，表明其在体内应用中具有良好的生物相容性和安全性。此外，提高内皮细胞（EC）的增殖导致 HPM 涂层支架组的支架覆盖率（即内皮化）明显高于 BMS 组，具有梭形 EC。这些结果表明，这种简便的涂层方法可以显著促进内皮化，并提供比 BMS 更高的安全性，因为它的抗血栓形成性能得到了极大的改善。此外，它可能为结合二次药物（如抗增殖药物）提供一个平台。
