Background: <p>Conventional drug-eluting stents suppress neointimal hyperplasia but delay re-endothelialization, raising long-term safety concerns. This study developed and evaluated a sirolimus–WKYMVm eluting stent (S-WES) to simultaneously promote re-endothelialization and suppress neointimal hyperplasia.</p> Methods: <p>Sirolimus-eluting stents (SES), WKYMVm-eluting stents (WES), and S-WES were fabricated using electrospray. Surface morphology was characterized via scanning electron microscopy (SEM), and in vitro drug-release kinetics were determined using high-performance liquid chromatography. Biological efficacy was assessed using human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) assays. In vivo performance was evaluated over 4&#xa0;weeks, followed by optical coherence tomography (OCT) and histopathological analysis.</p> Results: <p>SEM analysis showed that S-WES had a uniform, crack-free polymer coating. Each stent was consistently loaded with sirolimus (105.15 ± 25.54&#xa0;μg) and WKYMVm (1.07 ± 0.18&#xa0;μg), yielding a dual drug-release profile. WKYMVm was almost completely released within 7&#xa0;days, whereas sirolimus showed sustained release (day 1: 22.43 ± 5.32%, day 28: 94.38 ± 4.11%). In vitro assays showed that sirolimus suppressed SMC migration and HUVEC proliferation, while WKYMVm significantly enhanced HUVEC proliferation. In vivo OCT revealed reduced neointimal hyperplasia in the S-WES group (29.64 ± 8.66 μm<sup>2</sup>) compared with SES (34.65 ± 7.50 μm<sup>2</sup>; <i>p</i> = 0.041). Histopathology and immunohistology showed reduced stenosis ratio (28.39 ± 6.84%), decreased α-SMA expression, and increased VE-cadherin, CD31-positive endothelial coverage in the S-WES group.</p> Conclusion: <p>The sirolimus–WKYMVm dual-drug stent enhances re-endothelialization and inhibits neointimal hyperplasia, thereby offering a promising strategy for improving the efficacy and long-term safety of cardiovascular stents.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Dual-Drug Stent with Sirolimus and WKYMVm Promotes Endothelialization and Limits Hyperplasia

  • Yu Jeong Jin,
  • Dae Sung Park,
  • Myung Ho Jeong,
  • Doo Sun Sim,
  • Mi Hyang Na,
  • Chan Woo Kim,
  • Jeong Ha Kim,
  • Hae Jin Kee,
  • Young Joon Hong,
  • Kyung Hoon Cho,
  • Dae Young Hyun,
  • Seok Oh,
  • Jeong Hun Kim,
  • Dong-Weon Lee

摘要

Background:

Conventional drug-eluting stents suppress neointimal hyperplasia but delay re-endothelialization, raising long-term safety concerns. This study developed and evaluated a sirolimus–WKYMVm eluting stent (S-WES) to simultaneously promote re-endothelialization and suppress neointimal hyperplasia.

Methods:

Sirolimus-eluting stents (SES), WKYMVm-eluting stents (WES), and S-WES were fabricated using electrospray. Surface morphology was characterized via scanning electron microscopy (SEM), and in vitro drug-release kinetics were determined using high-performance liquid chromatography. Biological efficacy was assessed using human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) assays. In vivo performance was evaluated over 4 weeks, followed by optical coherence tomography (OCT) and histopathological analysis.

Results:

SEM analysis showed that S-WES had a uniform, crack-free polymer coating. Each stent was consistently loaded with sirolimus (105.15 ± 25.54 μg) and WKYMVm (1.07 ± 0.18 μg), yielding a dual drug-release profile. WKYMVm was almost completely released within 7 days, whereas sirolimus showed sustained release (day 1: 22.43 ± 5.32%, day 28: 94.38 ± 4.11%). In vitro assays showed that sirolimus suppressed SMC migration and HUVEC proliferation, while WKYMVm significantly enhanced HUVEC proliferation. In vivo OCT revealed reduced neointimal hyperplasia in the S-WES group (29.64 ± 8.66 μm2) compared with SES (34.65 ± 7.50 μm2; p = 0.041). Histopathology and immunohistology showed reduced stenosis ratio (28.39 ± 6.84%), decreased α-SMA expression, and increased VE-cadherin, CD31-positive endothelial coverage in the S-WES group.

Conclusion:

The sirolimus–WKYMVm dual-drug stent enhances re-endothelialization and inhibits neointimal hyperplasia, thereby offering a promising strategy for improving the efficacy and long-term safety of cardiovascular stents.