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Biomaterial-dependent neutrophil mobility and phagocytosis of bacteria in the mechanism of cardiovascular implant infection.

机译：生物材料依赖性中性粒细胞的迁移和细菌吞噬作用在心血管植入物感染的机制中。

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摘要

Infection is a potentially serious complication and a major impediment to the long-term clinical success of implanted cardiovascular devices. This thesis examined the hypothesis that foreign-body biomaterials and surface-associated host proteins cause attenuations in neutrophil mobility and phagocytosis that increase the probability for cardiovascular implant-related infection. Reduced neutrophil mobility and phagocytosis may prevent access and effective killing of bacteria, giving the bacteria sufficient opportunity to produce a biofilm.; To address the hypothesis, microscopic methods were used to provide quantitative comparisons of neutrophil mobility and phagocytic function on materials with different surface properties.; To test human neutrophil mobility, three materials were selected. These materials include a clinically relevant polyurethane (Chronoflex AR), a hydrophobic model surface consisting of an octadecyltrichlorosilane (OTS) self-assembled monolayer (SAM), and a glass reference material. Surface dependent neutrophil mobility was evaluated by time-lapse optical microscopy, confocal microscopy and atomic force microscopy (AFM). Our results show that material surface properties and surface adsorbed proteins are important in neutrophil mobility induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) stimulation. Without plasma protein adsorption, neutrophil mobility increased with increasing material surface hydrophobicity from glass, to polyurethane to OTS. With plasma protein adsorption, neutrophil mobility decreased with increasing material surface hydrophobicity from glass, Polyurethane to OTS surfaces. The decrease in neutrophil mobility under stimulation was directly related to increased cell spreading on the material substrates.; Neutrophil phagocytosis of Staphylococcus epidermidis on the three materials was recorded using time-lapse optical microscopy and compared based on the rate of bacteria ingestion. The morphology of adherent neutrophils was analyzed by fluorescence confocal microscopy. Our results show that on the materials without adsorbed plasma protein, neutrophil phagocytic ability increases from hydrophilic glass to hydrophobic OTS. In the presence of adsorbed plasma protein, neutrophil phagocytic ability increased on all the three materials, but was highest on the polyurethane. The results suggest that material surface properties and the surface adsorbed plasma proteins significantly affect phagocytic ability of surface adherent neutrophils.; The results from this thesis may be of value in designing biomaterials surface that improve bactericidal function of neutrophil and reduce implant-associated infection.
机译：感染是潜在的严重并发症，并且是植入式心血管设备长期临床成功的主要障碍。本论文检验了以下假说：异物生物材料和与表面相关的宿主蛋白会导致嗜中性粒细胞活动性和吞噬作用减弱，从而增加发生心血管植入物相关感染的可能性。中性粒细胞活动性和吞噬能力的降低可能会阻止细菌的进入和有效杀灭，使细菌有足够的机会产生生物膜。为了解决这个假设，使用显微镜方法对具有不同表面特性的材料的嗜中性白细胞迁移率和吞噬功能进行了定量比较。为了测试中性粒细胞的活动性，选择了三种材料。这些材料包括临床相关的聚氨酯（Chronoflex AR），由十八烷基三氯硅烷（OTS）自组装单层（SAM）组成的疏水模型表面，以及玻璃参考材料。通过延时光学显微镜，共聚焦显微镜和原子力显微镜（AFM）评估表面依赖性嗜中性白细胞的迁移率。我们的结果表明，材料表面性质和表面吸附蛋白在N-甲酰基甲硫基-亮氨酰-苯丙氨酸（fMLP）刺激诱导的嗜中性粒细胞迁移中很重要。没有血浆蛋白的吸附，嗜中性粒细胞的迁移率随从玻璃到聚氨酯再到OTS的材料表面疏水性的增加而增加。随着血浆蛋白的吸附，嗜中性粒细胞的迁移性随着从玻璃，聚氨酯到OTS表面的材料表面疏水性的增加而降低。刺激下嗜中性粒细胞迁移率的降低与细胞在物质基质上扩散的增加​​直接相关。使用延时光学显微镜记录了三种材料上的表皮葡萄球菌的嗜中性粒细胞吞噬作用，并根据细菌的摄入速率进行了比较。通过荧光共聚焦显微镜分析粘附的中性粒细胞的形态。我们的结果表明，在没有吸附血浆蛋白的材料上，嗜中性粒细胞的吞噬能力从亲水性玻璃提高到疏水性OTS。在存在吸附血浆蛋白的情况下，中性粒细胞的吞噬能力在所有三种材料上均增加，但在聚氨酯上最高。结果表明材料的表面性质和表面吸附的血浆蛋白显着影响表面粘附的中性粒细胞的吞噬能力。本论文的结果可能对设计可改善嗜中性粒细胞的杀菌功能并减少植入物相关感染的生物材料表面具有价值。

著录项

  • 作者

    Zhou, Yue.;

  • 作者单位

    Case Western Reserve University.;

  • 授予单位 Case Western Reserve University.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 200 p.
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

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