FOREIGN BODY REACTION AND DEVICE CENTERED INFECTION

异物反应和设备中心感染

• 批准号: 6527173
• 负责人: Liping Tang
• 金额: $ 24.31万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-11 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527173
• 关键词: Staphylococcus epidermidis; Staphylococcus infection; bacteria infection mechanism; biomaterial interface interaction; clinical research; fibrinogen; foreign body reaction; genetically modified animals; human subject; laboratory mouse; medical implant science; microorganism growth; phagocytes; polyethylenes; polyurethanes; polyvinyls; silicon compounds

The proposed studies are aimed at elucidating the mechanism(s) of foreign body responses and device-centered infection. Despite the widespread use of chronic implants, surprisingly little is known about the pathogenesis of biomaterial-mediated adverse responses. In fact, biomaterial-mediated foreign body reactions and infections may be associated with chronic discomfort, implant failure, and sometimes fatality. It is generally accepted that spontaneously adsorbed host proteins may influence subsequent tissue/cell responses. We earlier found that the spontaneous adsorption of fibrinogen triggers subsequent phagocyte accumulation. The portion of fibrinogen responsible for biomaterial-mediated phagocyte adhesion has recently been identified as a 13 amino acid sequence (gammal9O-202) which is recognized by the phagocyte integrin Mac-1. Because fibrinogen: Mac-1 interactions have been found to influence phagocyte responses, we have hypothesized that adsorbed fibrinogen may be critical to the prolonged survival of adherent bacteria, thereby promoting device-centered infection. In fact, we have very recently found that adsorbed fibrinogen does impair phagocyte bactericidal activity by reducing the release of phagocyte bactericidal products, such as superoxide, and indirectly promoting the survival of implant-associated Staphylococcus epidermidis. However, it is still unclear how adsorbed fibrinogen actually enhances the persistence of implant-associated bacteria and how particular surface properties influence both foreign body reactions and device-centered infection. To find the answer, we shall: (1) Determine which epitope(s) displayed by adsorbed fibrinogen are critical to the survival of adherent bacteria on polyethylene terephthalate (PET), (2) Investigate bactericidal activity of adherent phagocytes on surfaces precoated with different fibrinogen fragments and proteins. Finally, (3) using six commonly used biomaterials and a series of radio frequency glow discharge treated surfaces, we will study the influence of surface characteristics in the exposure of fibrinogen neo-epitopes, and the pathogenesis of foreign body reactions and device-centered infection. It is our hope that a more precise understanding of host:implant interactions and the mechanism of device-centered infection may permit the future rational design of biomaterials with markedly improved safety and tissue compatibility.

建议的研究旨在阐明异物反应和以装置为中心的感染的机制(S)。尽管慢性植入物被广泛使用，但令人惊讶的是，人们对生物材料介导的不良反应的发病机制知之甚少。事实上，生物材料介导的异物反应和感染可能与慢性不适、植入失败，有时甚至死亡有关。人们普遍认为，自发吸附的宿主蛋白可能会影响随后的组织/细胞反应。我们早些时候发现，纤维蛋白原的自发吸附触发了随后的吞噬细胞聚集。负责生物材料介导的吞噬细胞黏附的纤维蛋白原部分最近被确定为吞噬细胞整合素Mac-1识别的13个氨基酸序列(Gammar90-202)。由于纤维蛋白原：Mac-1的相互作用已被发现影响吞噬细胞的反应，我们假设吸附的纤维蛋白原可能是黏附细菌延长生存时间的关键，从而促进以设备为中心的感染。事实上，我们最近发现，吸附的纤维蛋白原确实通过减少吞噬细胞杀菌产物的释放，如超氧化物的释放，并间接促进植入物相关的表皮葡萄球菌的生存，从而削弱吞噬细胞的杀菌活性。然而，目前尚不清楚吸附的纤维蛋白原实际上是如何增强植入相关细菌的持久性的，以及特定的表面属性如何影响异物反应和设备中心感染。为了找到答案，我们将：(1)确定吸附的纤维蛋白原显示的哪个表位(S)对聚对苯二甲酸乙二酯(PET)上的黏附细菌的生存至关重要；(2)研究在预涂有不同纤维蛋白原片段和蛋白质的表面上黏附的吞噬细胞的杀菌活性。最后，使用六种常用生物材料和一系列射频辉光放电处理表面，研究表面特性对纤维蛋白原新表位暴露的影响，以及异物反应和设备中心感染的发病机制。我们希望，对宿主：种植体相互作用和以装置为中心的感染机制的更准确的理解，可以使未来的生物材料的合理设计具有明显改善的安全性和组织相容性。