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Engineering the Biomaterial Interface of Prosthetic Vascular Grafts for Improving Thromboresistance and Biocompatibility.

机译：设计人工血管移植物的生物材料界面，以改善血栓抵抗性和生物相容性。

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摘要

The purpose of this dissertation is to develop novel biomaterials as therapies for treating cardiovascular disease. The first and second aims describe the creation of a new and facile approach for grafting bioactive heparin to the surface of expanded polytetrafluoroethylene (ePTFE) vascular grafts using a thermally cross-linked poly(1,8 octanediol-co-citric acid) (POC) elastomer. The POC immobilized heparin (POC-Heparin) demonstrated excellent long term stability under physiological conditions for up to one month and significantly reduced platelet adhesion and maintained bioactive inhibition of whole blood clotting kinetics. POC-Heparin supported endothelial cell viability, proliferation, nitric oxide production and expression of endothelial cell specific markers von Willebrand factor and vascular endothelial-cadherin. This material was also capable of affecting vascular smooth muscle cell phenotype via increased expression of alpha-actin and decreased cell growth. The POC-Heparin coating is capable of significantly improving vascular graft thromboresistance, supporting endothelialization and inhibiting vascular smooth muscle cell growth. This coating technology can be easily adapted to modify other blood contacting devices for simultaneously reducing thrombogenicity and improving endothelialization. Lastly, the third aim details the initial steps for developing materials which are capable of providing sustained release of bioactive signaling molecules such as stromal derived factor-1alpha (SDF-1) to promote recruitment of stem/progenitor cells. A copolymer based on citric acid, polyethylene glycol and N-isopropylacrylamide (CPN) was synthesized with enhanced electronegative charge and gelation properties for controlling SDF-1 protein encapsulation and delivery. Upon CPN gelation at 37°C, SDF-1 protein can be encapsulated with near 100% efficiency and deliver protein for up to 3 weeks. Using isolated blood outgrowth endothelial cells (BOECs) from human peripheral blood EPCs as a model for progenitor cell recruitment, the cells exhibited high levels of CXCR4 expression and demonstrated that released SDF-1 protein remained bioactive and was capable of promoting migration. The copolymer also exhibited excellent cell compatibility and significantly inhibited whole blood clotting. Together, these results are significant steps towards developing biocompatible materials which are capable of harnessing the regenerative properties of EPCs as well as serving as thromboresistant blood vessel replacements.
机译：本文的目的是开发新型的生物材料作为心血管疾病的治疗方法。第一个目标和第二个目标描述了一种使用热交联的聚（1,8辛二醇-柠檬酸）（POC）将生物活性肝素移植到膨胀的聚四氟乙烯（ePTFE）血管移植物表面的新方法，该方法简便易行。弹性体。固定化POC的肝素（POC-肝素）在生理条件下长达一个月表现出出色的长期稳定性，并显着降低了血小板粘附，并保持了对全血凝血动力学的生物活性抑制。 POC-肝素支持内皮细胞的活力，增殖，一氧化氮的产生以及内皮细胞特异性标记von Willebrand因子和血管内皮钙粘蛋白的表达。这种材料还能够通过增加α-肌动蛋白的表达和减少细胞的生长来影响血管平滑肌细胞表型。 POC-肝素涂层能够显着提高血管移植物的血栓抵抗力，支持内皮化并抑制血管平滑肌细胞的生长。这种涂层技术可以轻松地修改其他血液接触装置，以同时降低血栓形成性并改善内皮化。最后，第三个目标详述了开发能够提供生物活性信号分子（例如基质衍生因子-1α（SDF-1））持续释放以促进干细胞/祖细胞募集的材料的初始步骤。合成了基于柠檬酸，聚乙二醇和N-异丙基丙烯酰胺（CPN）的共聚物，该共聚物具有增强的负电性和胶凝性，可控制SDF-1蛋白的包封和递送。在37°C下CPN凝胶化后，SDF-1蛋白可以以接近100％的效率被封装，并可以递送蛋白质长达3周。使用来自人外周血EPC的分离的血液生长内皮细胞（BOEC）作为祖细胞募集的模型，这些细胞表现出高水平的CXCR4表达，并证明释放的SDF-1蛋白仍然具有生物活性并能够促进迁移。该共聚物还表现出优异的细胞相容性，并显着抑制了全血凝块。总之，这些结果是开发生物相容性材料的重要步骤，该材料能够利用EPC的再生特性并用作抗血栓性血管替代品。

著录项

  • 作者

    Hoshi, Ryan Akihiro.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Engineering Biomedical.;Engineering Materials Science.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 254 p.
  • 总页数 254
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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