The Cardiovascular Convergence Research Center of Chonnam National University Hospital Designated by Korea wMinistry of Health and Welfare, Gwangju, 501-757, Republic of Korea.
Korea Cardiovascular Stent Research Institute, Jangsung, 501-893, Republic of Korea.
J Biomed Mater Res B Appl Biomater. 2018 May;106(4):1486-1495. doi: 10.1002/jbm.b.33955. Epub 2017 Jul 10.
The aim of this study was to evaluate the effects of bilirubin- and/or everolimus (EVL)-coated stents to prevent arterial neointimal hyperplasia and inflammation in vitro and in vivo. The stents were prepared by spray coating bare metal stents (BMS) with bilirubin and/or EVL. Study groups were divided into (1) BMS, (2) bilirubin-coated stents (BES), (3) commercialized stents (Synergy™; EES), and (4) bilirubin/EVL-coated stents (B-EES). The coating thickness and drug release rates were comparable to previous reports (i.e., <4 µm thickness and 50% drug release in 7 days). Smooth muscle cell migration was inhibited in both EVL-containing groups (20.5 ± 3.80% in EES and 18.4 ± 2.55% in B-EES) compared to the non-EVL-containing groups (78.0 ± 6.41% in BMS and 76.1 ± 4.88% in BES) (n = 10, p < 0.05). Stents were randomly implanted to 40 coronary arteries in 20 pigs and subjected to various analyses after 4 weeks of implantation. As results, the inflammation score was dramatically increased in the EES group (2.1 ± 0.42) compared to that of the other groups (1.5 ± 0.55, 1.3 ± 0.23, and 1.5 ± 0.27 for BMS, BES, and B-EES, respectively, n = 10, p < 0.05). Immunofluorescence analysis revealed that inflammation was prevented in the bilirubin-containing groups (BES and B-EES). However, the percent area of restenosis was decreased in the EVL-containing groups (20.5 ± 4.11% for EES and 18.4 ± 3.61% for B-EES) compared to the non-EVL-containing groups (32.3 ± 6.41% for BMS and 29.6 ± 5.95% for BES, n = 10, p < 0.05). The percent areas of restenosis determined by histopathology, optical coherence tomography, and micro-computed tomography were consistent. In addition, the stent was barely covered in the EES and B-EES groups at 4 weeks postimplantation. These dual drug-coated stents may be especially beneficial to patients who have an increased risk of inflammation. These stents have great potential for use in cardiovascular applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1486-1495, 2018.
本研究旨在评估胆红素和/或依维莫司（EVL）涂层支架预防体外和体内动脉新生内膜增生和炎症的效果。支架通过喷涂胆红素和/或 EVL 来制备。研究组分为（1）BMS、（2）胆红素涂层支架（BES）、（3）商业化支架（Synergy™；EES）和（4）胆红素/依维莫司涂层支架（B-EES）。涂层厚度和药物释放率与之前的报告相当（即，<4 µm 厚度和 7 天内 50%药物释放）。与非 EVL 组（BMS 组为 78.0 ± 6.41%，BES 组为 76.1 ± 4.88%）相比，两种 EVL 支架组（EES 组为 20.5 ± 3.80%，B-EES 组为 18.4 ± 2.55%）的平滑肌细胞迁移受到抑制（n = 10，p < 0.05）。将支架随机植入 20 头猪的 40 条冠状动脉内，并在植入后 4 周进行各种分析。结果显示，EES 组的炎症评分显著升高（2.1 ± 0.42），而其他组（BMS 组、BES 组和 B-EES 组分别为 1.5 ± 0.55、1.3 ± 0.23 和 1.5 ± 0.27，n = 10，p < 0.05）。免疫荧光分析显示，胆红素组（BES 和 B-EES）炎症得到了预防。然而，与非 EVL 组（BMS 组为 32.3 ± 6.41%，BES 组为 29.6 ± 5.95%）相比，EVL 组（EES 组为 20.5 ± 4.11%，B-EES 组为 18.4 ± 3.61%）的再狭窄百分比降低（n = 10，p < 0.05）。组织病理学、光学相干断层扫描和微计算机断层扫描确定的再狭窄百分比是一致的。此外，EES 和 B-EES 组在植入后 4 周时支架几乎没有被覆盖。这些双药物涂层支架可能对炎症风险增加的患者特别有益。这些支架在心血管应用中具有很大的潜力。© 2017 Wiley Periodicals, Inc. J 生物材料 Res 部分 B：应用生物材料，106B：1486-1495，2018 年。
