Bilirubin coating attenuates the inflammatory response to everolimus‐coated stents. Issue 4 (10th July 2017)

• Record Type: Journal Article
• Authors: Bae, In‐Ho; Park, Dae Sung; Lee, So‐Youn; Jang, Eun‐Jae; Shim, Jae‐Won; Lim, Kyung‐Seob; Park, Jun‐Kyu; Kim, Ju Han; Sim, Doo Sun; Jeong, Myung Ho
• Is Part Of: Journal of biomedical materials research. Volume 106:Issue 4(2018)
• Page Start: 1486
• Page End: 1495
• Publication Date: 2017-07-10
• Subjects: bilirubin -- everolimus -- drug‐eluting stent -- anti‐inflammation -- antirestenosis; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/jbm.b.33955
• Languages: English
• ISSNs: 1552-4973

Abstract

Abstract: 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.