The characteristics and in vivo suppression of neointimal formation with sirolimus-eluting polymeric stents
The characteristics and in vivo suppression of neointimal formation with sirolimus-eluting polymeric stents
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DOI：
10.1016/j.biomaterials.2008.09.006
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发表时间：
2009-01-01
期刊：
影响因子：
14
通讯作者：
Sung, Hsing-Wen
中科院分区：
文献类型：
--
作者：
Chen, Mei-Chin;Chang, Yen;Sung, Hsing-Wen
药物洗脱支架已成为冠状动脉疾病患者的主要经皮策略。然而，由其不可腐蚀的聚合物涂层和裸金属支架引起的超敏反应可能导致严重的临床后遗症。在本报告中，开发了一种新的可生物降解的西罗莫司洗脱支架，该支架由环氧化合物固定的壳聚糖基条带制成，并涂有疏水肝素。由于在支架基质中形成的共价交联，所制造的支架具有形状记忆性质以记忆其永久形状。提高支架的交联度可以提高支架的形状记忆能力和机械强度。支架的细胞相容性在体外被证明。支架上的肝素涂层有效地降低了血小板粘附;此外，它还起到了扩散屏障的作用，导致西罗莫司的缓释曲线接近线性。细胞周期分析表明，释放的西罗莫司可通过诱导细胞周期停滞在G_1期来抑制平滑肌细胞增殖。与未装载支架相比，在兔肾下腹部动脉瘤中植入西罗莫司洗脱支架后，新生内膜形成受到显著抑制。这些发现表明，开发的西罗莫司洗脱聚合物支架可以成为治疗动脉粥样硬化的潜在替代方案。(C)2008爱思唯尔有限公司保留所有权利。
Drug-eluting stents have emerged as a predominant percutaneous strategy in patients with coronary artery disease. However, hypersensitivity reactions caused by their nonerodable polymer coatings and bare-metal stents may result in serious clinical sequelae. In this report, a new biodegradable sirolimus-eluting stent, made from chitosan-based strips fixed by an epoxy compound, coated with a hydrophobic heparin was developed. Due to the covalent crosslinks formed in the stent matrix, the fabricated stent had a shape-memory property to memorize its permanent shape. The shape-memory ability and mechanical strength of the stent could be enhanced by increasing its degree of crosslinking. The cyto-compatibility of the stent was demonstrated in vitro. The heparin coating on the stent effectively reduced platelet adhesion; additionally, it acted as a diffusion barrier and led to a nearly linear sustained-release profile of sirolimus. Cell-cycle analysis demonstrated that the released sirolimus could inhibit smooth muscle cell proliferation by inducing cell-cycle arrest in G, phase. When compared to the unloaded stent, neointimal formation was significantly suppressed after implantation of the sirolimus-eluting stent in rabbit infrarenal abdominal aortas. These findings suggested that the developed sirohmus-eluting polymeric stent can be a potential alternative for treatment of atherosclerosis. (C) 2008 Elsevier Ltd. All rights reserved.