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Engineering biomaterial interfaces to control foreign body response: Reducing giant cell formation and understanding host response to porous materials.

机译:工程生物材料界面可控制异物反应:减少巨细胞形成并了解宿主对多孔材料的反应。

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摘要

All implanted devices and sensors are subject to the foreign body reaction, a cascade of events ultimately leading to chronic inflammation, device encapsulation, and impaired healing. We propose two approaches to alter the course of events and improve the fate of implants. First we show that osteopontin, a natural protein involved with bone homeostasis and wound healing, plays a role in regulation of foreign body giant cells. We are the first to show that absence of osteopontin increases macrophage fusion in response to biomaterial implants in vivo and the protein's ability to reduce foreign body giant cell formation in vitro. This suggests that presentation of this protein, either by surface immobilization or by controlled release, may reduce giant cell presence and the damage they induce to implants. Second we carefully study the effects of porosity on host response by analyzing in vivo phenotypic and genetic reactions to scaffolds possessing controlled, regular, highly interconnected pore structures. Previous studies have shown that at four weeks post-implantation, peak angiogenesis was observed in scaffolds with pore diameters around 35mum. We studied expression of genes at earlier timepoints which may contribute to the observed differences. Determination of genes key to angiogenesis at implant sites and their temporal profiles can aid rational design of future biomaterials and controlled release systems.
机译:所有植入的设备和传感器均会受到异物反应,一系列事件最终导致慢性炎症,设备封装和愈合受损。我们提出了两种方法来改变事件的进程并改善植入物的命运。首先,我们表明骨桥蛋白是一种涉及骨稳态和伤口愈合的天然蛋白质,在调节异物巨细胞中发挥作用。我们是第一个表明骨桥蛋白的缺失会增加体内巨噬细胞对生物材料植入物的反应,以及该蛋白质在体外减少异物巨细胞形成的能力。这表明通过表面固定或通过控制释放来表达这种蛋白质,可以减少巨细胞的存在以及它们对植入物的诱导损害。其次,我们通过分析具有受控,规则,高度相互连接的孔结构的支架的体内表型和遗传反应,仔细研究了孔隙度对宿主反应的影响。先前的研究表明,在植入后四周,在直径约35μm的支架中观察到了峰值血管生成。我们研究了在较早时间点的基因表达,这可能有助于观察到的差异。确定对植入部位血管生成至关重要的基因及其时间分布,可以帮助合理设计未来的生物材料和控释系统。

著录项

  • 作者

    Tsai, Annabel T.;

  • 作者单位

    University of Washington.;

  • 授予单位 University of Washington.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 134 p.
  • 总页数 134
  • 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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