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Nitric oxide synthase-based biopolymers; towards novel thromboresistant no-release materials.

机译:一氧化氮合酶基生物聚合物;面向新型抗血栓的不释放材料。

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摘要

Nitric Oxide releasing biopolymers have the potential to prolong vascular graft and stent potency without adverse systemic vasodilation. It was reported in literature that eNOS-overexpressing endothelial cell seeding of synthetic small diameter vascular grafts decreased human platelet aggregation by 46% and bovine aortic smooth muscle cell proliferation by 67.2% in vitro. We hypothesized that incorporating the enzyme nitric oxide synthase (NOS) in biocompatible polymeric matrix will provide a source of NO that utilizes endogenous compounds to maintain an unlimited supply of NO. To test this hypothesis, we have incorporated the enzyme nitric oxide synthase into a polyethyleneimine film using a layer-by-layer electrostatic deposition. This approach will provide a source of NO that utilizes endogenous compounds available in the blood matrix to maintain a constant supply of NO at the blood/device interface. When coated onto the surface of various blood-contacting implantable medical devices, it will provide NO fluxes at levels equal or greater than the normal endothelial cells, and for extended time periods. This configuration will help solve the issues of both thrombosis and stenosis that occur as side effects for several types of biomedical implants.;Our results indicate a proof of principle of a new approach for making antithrombotic coatings for medical devices and implants based on NO release. We have demonstrated that NOS-based polymetric films successfully generate NO under physiologic conditions at small levels equal to and higher than those observed for endothelial cells. The level of NO release can be fine-tuned through varying the number of NOS layers in the film buildup. We have shown that NO fluxes from our NOS-based PEI films are sustained for prolonged periods of time, which has the potential of producing efficient, short and long-term, antithrombotic coatings for medical devices and blood-contacting tools such as stents and catheters. We also show that NO release from these coatings successfully decrease platelet adhesion at the surface by 60%. This, and other properties are key for the desired thromboresistivity needed for blood-contacting medical devices.
机译:释放一氧化氮的生物聚合物具有延长血管移植物和支架效能而不会引起不利的全身血管舒张的潜力。有文献报道,在体外,合成的小直径血管移植物过表达eNOS的内皮细胞可减少46%的人血小板聚集和67.2%的牛主动脉平滑肌细胞增殖。我们假设将酶一氧化氮合酶(NOS)掺入生物相容性聚合物基质中将提供NO的来源,该来源利用内源性化合物来保持无限的NO供应。为了检验该假设,我们使用一层静电沉积将一氧化氮合酶掺入聚乙烯亚胺膜中。这种方法将提供一氧化氮的来源,该来源利用血液基质中可用的内源性化合物来维持血液/装置界面处一氧化氮的稳定供应。当涂在各种与血液接触的可植入医疗设备的表面上时,它将提供与正常内皮细胞相同或更高水平的NO通量,并且持续时间较长。这种配置将有助于解决由于多种类型的生物医学植入物而引起的血栓形成和狭窄问题。我们的结果表明了一种基于NO释放制造用于医疗器械和植入物的抗血栓涂层的新方法的原理证明。我们已经证明,基于NOS的多谱膜可以在生理条件下成功产生NO,其水平等于或高于内皮细胞所观察到的水平。可以通过改变膜层中NOS层的数量来微调NO释放的水平。我们已经表明,基于NOS的PEI膜的NO流量会持续较长时间,这有可能为医疗设备和血液接触工具(如支架和导管)生产高效,短期和长期的抗血栓涂层。我们还表明,从这些涂层释放的NO成功地将血小板在表面的粘附力降低了60%。对于与血液接触的医疗设备所需的所需血栓形成电阻率,此特性和其他特性至关重要。

著录项

  • 作者

    Diwan, Charbel Abou.;

  • 作者单位

    Cleveland State University.;

  • 授予单位 Cleveland State University.;
  • 学科 Chemistry Pharmaceutical.;Chemistry Polymer.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 174 p.
  • 总页数 174
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药物化学;高分子化学(高聚物);
  • 关键词

  • 入库时间 2022-08-17 11:38:26

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