Wear, Inflammation and Clinical Performance of Total Disc Replacement

描述(由申请人提供)：退行性腰椎间盘疾病是一种痛苦的、致残的情况。20世纪60年代，全椎间盘置换(TDR)被认为是脊柱融合及其并发症的替代治疗方法。现在，经过20年在欧洲的临床应用和美国FDA的批准，TDR和植入物设计的结果可以评估。装置回收研究的一个基本目标是通过外植体分析了解成功的种植体和评估失败的种植体。TDR的失效机制可能与设计有关和/或由材料退化引起。设备失效的潜在机制来自对完全关节替换(TJR)的研究。许多TJR故障是由于部件降解、磨屑产生和炎症反应的刺激。与TJRs不同的是，人们对人工椎间盘的体内降解或磨屑对生物介导的失效机制的贡献知之甚少。我们在这里提供的证据表明，TDR表现出表面损伤，如轮缘断裂、分层、聚乙烯(PE)渗透和体内氧化。我们已经建立了使用MicroCT分析来量化TDR部件中的线磨损和体积磨损的方法。此外，我们有一种方法来评估假体周围组织中磨损颗粒的体积、形状和大小，并显示出磨屑的数量与炎症和组织病理学变化的程度呈正相关，这可能是TDR失败的主要原因，如异位骨化(HO)和顽固性疼痛。为了研究TDR的潜在失效模式，我们建议阐明体内降解的机制以及磨屑在生物介导的失效机制中的贡献。首先，我们将评估TDR种植体的物理变化，以确定三种TDR设计(两种当代设计和一种历史对照)在磨损率和磨损率方面是否存在显著差异。将为三种TDR设计确定与植入物磨损相关的重大物理变化。其次，我们将评估回收的TDR假体周围组织中磨损颗粒的体积、形状和大小分布，并确定这些发现是否与TDR设计显著相关。最后，我们将评估假体周围组织的炎症反应(骨和神经炎症介质)和组织学反应，并将这些变化与PE磨屑的存在和临床TDR失败相关联。}成功实现拟议的特定目标将提供有关植入物性能和设计的基本信息，{以及潜在的生物介体，可用于防止由于疼痛而丧失植入物的移动性和翻修手术的需要。此外，它还将提供做出明智的医疗保健决策所需的基本信息。 公共卫生相关性：全椎间盘置换(TDR)于1960年构思，现在，在欧洲临床使用20年，在美国使用10年后，TDR和植入物设计的长期和短期结果可以评估。我们设备回收研究的一个基本目标是通过外植体、组织和临床分析来了解成功的植入物和评估失败的植入物。因此，拟议研究的成功完成将提供有关TDR植入物性能和临床结果的基本信息，这是知情的医疗保健决策所必需的。

DESCRIPTION (provided by applicant): Degenerative disc disease is a painful, disabling condition. In the 1960s, total disc replacement (TDR) was conceived as an alternative treatment to spinal fusion and the resulting complications. Now, after two decades of clinical use in Europe, and FDA approval in the US, the outcomes of TDR and implant design can be assessed. A fundamental objective of device retrieval research is to understand successful implants and assess failures through explant analysis. Failure mechanisms of TDRs may be design-related and/or result from material degradation. Potential mechanisms of device failure come from studies on total joint replacements (TJR). Many TJR failures are due to component degradation, wear debris generation and the stimulation of an inflammatory response. In contrast to TJRs, little is known about in vivo degradation or the contribution of wear debris to biologically-mediated failure mechanisms of artificial discs. We provide evidence here that TDRs exhibit surface damage such as rim fracture, delamination, polyethylene (PE) penetration and in-vivo oxidation. We have established methods to quantify linear wear and volumetric wear in TDR components using microCT analysis. Moreover, we have a method to evaluate the volume, shape and size of wear particles in periprosthetic tissues using environmental scanning electron microscopy and have shown a positive correlation between the amount of debris and the extent of the inflammatory and histopathologic changes, which { may contribute to the major reasons for TDR failure, e.g. heterotopic ossification (HO) and intractable pain. } To investigate the potential failure modes of TDRs, we propose to elucidate mechanisms of in vivo degradation and the contribution of wear debris to biologically-mediated failure mechanisms. First, we will evaluate physical changes of TDR implants to determine if there are significant differences in wear and wear rate among three TDR designs (two contemporary designs and a historical control). The physical changes that are significant with respect to implant wear will be established for the three TDR designs. Second, we will evaluate the volume, shape and size distribution of wear particles in periprosthetic tissue of retrieved TDRs and determine if these findings are significantly correlated to TDR design. Lastly, we will evaluate the inflammatory { (osteo- and neuro-inflammatory mediators) } and histological responses in periprosthetic tissues and correlate these changes to the presence of PE wear debris { and clinical TDR failure. } Successful achievement of the proposed specific aims will provide essential information about implant performance and design, { and potential biological mediators that can be targeted to prevent the loss of implant mobility and the need for revision surgery due to pain. In addition, it } will provide essential information needed for informed health care decisions. PUBLIC HEALTH RELEVANCE: Total disc replacement (TDR) was conceived in 1960 and now, after two decades of clinical use in Europe and a decade in the United States, the long-term and short-term outcomes of TDR and implant design can be assessed. A fundamental objective of our device retrieval research is to understand successful implants and assess failures through explant, tissue and clinical analysis. Thus, successful achievement of the proposed research will provide essential information on TDR implant performance and on clinical outcomes, which are needed for informed health care decisions.