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Evaluation of the effect of expansion and shear stress on a self-assembled endothelium mimicking nanomatrix coating for drug eluting stents in vitro and in vivo

机译:在体外和体内评价膨胀和剪切应力对模拟药物洗脱支架的自组装内皮模拟纳米基质涂层的影响

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摘要

Coating stability is increasingly recognized as a concern impacting the long-term effectiveness of drug eluting stents (DES). In particular, unstable coatings have been brought into focus by a recently published report (Denardo et al 2012 J. Am. Med. Assoc. 307 2148–50). Towards the goal of overcoming current challenges of DES performance, we have developed an endothelium mimicking nanomatrix coating composed of peptide amphiphiles that promote endothelialization, but limit smooth muscle cell proliferation and platelet adhesion. Here, we report a novel water evaporation based method to uniformly coat the endothelium mimicking nanomatrix onto stents using a rotational coating technique, thereby eliminating residual chemicals and organic solvents, and allowing easy application to even bioabsorbable stents. Furthermore, the stability of the endothelium mimicking nanomatrix was analyzed after force experienced during expansion and shear stress under simulated physiological conditions. Results demonstrate uniformity and structural integrity of the nanomatrix coating. Preliminary animal studies in a rabbit model showed no flaking or peeling, and limited neointimal formation or restenosis. Therefore, it has the potential to improve the clinical performance of DES by providing multifunctional endothelium mimicking characteristics with structural integrity on stent surfaces.
机译:人们日益认识到,涂层稳定性是影响药物洗脱支架(DES)长期有效性的一个问题。尤其是,最近发表的报告(Denardo等,2012 J. Am。Med。Assoc。307 2148–50)引起了不稳定涂料的关注。为了克服目前DES性能挑战的目标,我们开发了一种模仿纳米基质的内皮涂层,该涂层由能促进内皮化但限制平滑肌细胞增殖和血小板粘附的肽两亲物组成。在这里,我们报道了一种新颖的基于水蒸发的方法,该方法使用旋转涂层技术将模拟纳米基质的内皮均匀地涂覆到支架上,从而消除了残留的化学物质和有机溶剂,并易于应用于甚至可生物吸收的支架。此外,在模拟的生理条件下,在膨胀和剪切应力作用下经历的力之后,分析了模拟纳米基质的内皮的稳定性。结果证明了纳米基质涂层的均匀性和结构完整性。在兔模型中进行的初步动物研究显示,未出现剥落或剥落,并且仅出现有限的新内膜形成或再狭窄。因此,通过在支架表面上提供具有结构完整性的多功能内皮模拟特性,它有可能改善DES的临床性能。

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