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首页> 外文学位 >Elastin-like Polypeptide Enriched Surfaces for Cardiovascular Applications through the use of Bioactive Fluorinated Surface Modifiers.
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Elastin-like Polypeptide Enriched Surfaces for Cardiovascular Applications through the use of Bioactive Fluorinated Surface Modifiers.

机译：通过使用生物活性氟化表面改性剂，在心血管应用中富含弹性蛋白的多肽表面。

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摘要

Currently used small diameter synthetic vascular grafts are prone to high rates of failure related to thrombosis and neointimal hyperplasia. Biomimetic materials, based on the extracellular matrix (ECM) composition of native tissues, represent an attractive solution to address these complications. The inherent low thrombogenicity and cell signalling properties of elastin-like polypeptides (ELPs) make them a suitable option for these applications.;In this thesis, ELP surface modification has been achieved through the use of elastin cross-linking peptide bioactive fluorinated surface modifiers (ECP-BFSMs). The synthesis of these low molecular weight fluorinated additives was described and their subsequent blending with a base polycarbonate-urethane (PCNU) was shown to successfully enrich the surface to allow for ELP surface cross-linking. The kinetic surface migration of fluorescent ECP-BFSMs was studied over a 2 week casting period by two-photon confocal microscopy. Contact angle and x-ray photoelectron spectroscopy (XPS) confirmed the surface localization of the ECP-BFSMs. Changes in contact angle and XPS spectrums following ELP surface cross-linking confirmed the success of the surface modification approach.;The novel ELP surface modified materials were demonstrated to inhibit fibrinogen surface adsorption and platelet adhesion under physiological flow conditions and inhibit bulk platelet activation following blood-material contact. Moreover, these ELP modified surfaces were shown to promote increased endothelial and smooth muscle cell adhesion, spreading and retention over a 7 day culture period relative to their non-ELP analogs. Endothelial and smooth muscle cells seeded on the elastin-like materials were shown to express endothelial nitric oxide synthase (eNOS) and smooth muscle myosin heavy chain (SM-MHC) cell specific phenotypic markers, respectively. Furthermore, competitive inhibition experiments revealed that initial smooth muscle cell adhesion to ELP surface modified materials was mediated through elastin-laminin cell surface receptors binding to VGVAPG peptide sequences on the ELP molecules. Hence, these materials may have broad applicability in cardiovascular applications, from blood contacting materials to scaffold structures for vascular graft tissue engineering. Furthermore, this surface modifying additive approach represents a versatile technique that can be custom tailored for various biomimetic applications to generate stable bioactive ECM-like surfaces retained onto a relatively inert fluorinated background.
机译：当前使用的小直径合成血管移植物易于发生与血栓形成和新内膜增生有关的高失败率。基于天然组织的细胞外基质（ECM）组成的仿生材料代表了解决这些并发症的有吸引力的解决方案。弹性蛋白样多肽（ELP）固有的低血栓形成性和细胞信号转导特性使其成为这些应用的合适选择。在本论文中，通过使用弹性蛋白交联肽生物活性氟化表面修饰剂实现了ELP表面修饰（ ECP-BFSM）。描述了这些低分子量氟化添加剂的合成，并显示了它们随后与基础聚碳酸酯-氨基甲酸酯（PCNU）的共混能够成功地丰富表面，从而实现ELP表面交联。荧光ECP-BFSMs的动力学表面迁移在两周的铸造时间内通过双光子共聚焦显微镜进行了研究。接触角和X射线光电子能谱（XPS）证实了ECP-BFSM的表面定位。 ELP表面交联后接触角和XPS光谱的变化证实了该表面修饰方法的成功。新型ELP表面修饰材料在生理流动条件下可抑制纤维蛋白原表面吸附和血小板粘附，并在血液后抑制大量血小板活化物质接触。而且，相对于其非ELP类似物，这些ELP修饰的表面显示在7天的培养期内促进内皮和平滑肌细胞粘附，分布和保留的增加。弹性蛋白样材料上植入的内皮细胞和平滑肌细胞分别表达内皮一氧化氮合酶（eNOS）和平滑肌肌球蛋白重链（SM-MHC）细胞特异性表型标记。此外，竞争性抑制实验表明，最初的平滑肌细胞对ELP表面修饰物质的粘附是通过与ELP分子上的VGVAPG肽序列结合的弹性蛋白-粘蛋白细胞表面受体介导的。因此，这些材料在心血管应用中可能具有广泛的适用性，从血液接触材料到用于血管移植组织工程的支架结构。此外，这种表面改性添加剂方法代表了一种通用技术，可以针对各种仿生应用量身定制该技术，以生成保留在相对惰性氟化背景上的稳定的生物活性ECM样表面。

著录项

  • 作者

    Blit, Patrick Herve.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biomedical engineering.;Materials science.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 219 p.
  • 总页数 219
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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