Determination of excessive immune reactivity to real time implant debris generate

确定对实时种植体碎片产生的过度免疫反应

• 批准号: 9455400
• 负责人: Nadim James Hallab
• 金额: $ 23.55万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9455400
• 关键词: Alloys; Biocompatible Materials; Biological; Bioreactors; Cells; Chemicals; Chromium; Clinical; Cobalt; Communities; Complex; Corrosion; Development; Device Designs; Devices; Environment; Equilibrium; Friction; Future; Genes; Goals; Grant; Granuloma; Immune; Immune response; Immunological Models; Implant; In Situ; Industry; Inflammasome; Investigation; Ions; Knowledge; Lubricants; Lymphocyte; Mediating; Metals; Methods; Motion; Necrosis; Orthopedics; Osteoclasts; Particulate; Partner in relationship; Phase; Preclinical Testing; Predictive Value; Principal Investigator; Prosthesis Design; Proteins; Reaction; Reactive Oxygen Species; Salts; Signal Transduction; Stimulus; Surface; T-Lymphocyte; Testing; Time; Tissues; Titanium; base; bone; bone prosthesis; cell type; chromium hexavalent ion; clinically relevant; combat; design; immunoreaction; immunoreactivity; improved; in vitro Model; in vitro testing; in vivo; macrophage; metal complex; next generation; novel; particle; pre-clinical; precursor cell; programs; response; stem; tool; tumor

PROJECT SUMMARY Adverse local tissue reactions (ALTRs) associated with metal particulate debris and/or ions released from modular junctions and other metal interfaces (e.g. prosthesis/bone) are the result of immune responses which have presented as granulomas, necrotic tissue, pseudotumors, etc. Although wear and corrosion (‘tribocorrosion’) have long been recognized as the problems endangering the long term survival of orthopedic implants, much remains unknown about the interaction of host tissue with degradation products. We hypothesize that metal degradation products resulting from tribocorrosion are dynamically bioreactive (i.e. time-dependent), where implant debris is initially highly bioreactive and then decreases over time as it becomes more electrochemically stable. Once validated in this study, our development of a “Tribocorrosion Bioreactor” will allow direct mechanistic investigations between degradation products and cells, and will enable preclinical testing of meta-stable tribocorrosion products that are generated in situ. Here, we will evaluate if real time metal tribocorrosion products are excessively reactive aseptic stimuli eliciting both innate (macrophage) and adaptive (lymphocyte) immuno-reactivity and, thus, differ from more time-stabilized complexes formed from the same debris. Demonstrating the phenomenon of time-dependent implant debris reactivity is critical to understanding the clinical impact of freshly produced metal implant debris from both wear and corrosion. It will provide a significant leap forward into the next generation of in vitro testing of orthopedic materials.

项目总结 与金属微粒碎片和/或离子相关的不良局部组织反应 从模块连接和其他金属接口(例如假体/骨)释放出来的结果是 表现为肉芽肿、坏死组织、假瘤等的免疫反应。 尽管磨损和腐蚀(摩擦腐蚀)一直被认为是问题所在 危及骨科植入物的长期存活，许多人仍然不知道 宿主组织与降解产物的相互作用。我们假设金属的退化 摩擦腐蚀产生的产物是动态生物活性的(即依赖于时间)，其中 植入物碎片最初具有高度的生物活性，然后随着时间的推移逐渐减少 电化学性质稳定。一旦在这项研究中得到证实，我们开发的“摩擦腐蚀” 生物反应器“将允许在降解产物和细胞之间进行直接的机械研究， 并将实现亚稳定摩擦腐蚀产品的临床前测试，这些产品是在 SITE。在这里，我们将评估实时金属摩擦腐蚀产品是否过度活性 激发天然(巨噬细胞)和获得性(淋巴细胞)免疫反应性的无菌刺激 因此，不同于由相同碎片形成的更多时间稳定的复合体。 证明植入物碎片反应性随时间变化的现象对于 了解新生产的金属种植体磨屑对临床的影响 腐蚀。它将为下一代体外测试提供一个重要的飞跃 整形外科材料。