Wear Analysis of Intervertebral Total Disc Replacements

描述（由申请人提供）：椎间全椎间盘置换（TOR）植入物可能预示着退行性椎间盘疾病治疗的范式转变。保留运动可以避免邻近节段退变，这是一种公认的并发症积液。根据欧洲令人鼓舞的经验和目前结束的IDE试验，FDA可能在2005年初/中期批准两种领先的设计：Charite III和ProDisc。作为核聚变的替代方案（在美国每年约33万），这些设备的大量使用似乎迫在眉睫。后期磨损相关并发症的可能性令人担忧。两种器械均涉及金属对传统聚乙烯关节面，TDR患者人群比THR/TKR患者人群年轻10岁。此外，由于靠近脊髓，植入物失效的潜在后果比THR/TKR严重得多。科学界必须迅速正视TDR磨损问题。生物工程研究伙伴关系的建议，以提供一个坚实的科学基础，识别和处理与磨损有关的问题，在TDR。目的1是开发在临床前阶段进行TDR磨损评估的技术。这将利用互补的数值和物理技术：滑动距离耦合有限元分析（爱荷华州）和伺服控制实验室模拟（利兹）。目的2是实施一种新的体内TDR放射学磨损测量方法（爱荷华州），使用高分辨率数字图像分析评估植入物金属终板的相对三维姿势位置。在记录准确度/精密度后，将使用姿势图像分析技术测量欧洲最大/持续时间最长的TDR系列之一（慕尼黑）的磨损。目的3是评估TDR磨屑（利兹）的功能生物活性。形态学上逼真的模拟器产生的碎片将用于挑战培养制备物中的细胞，该培养制备物专门用于反映局部脊柱环境，将从该培养制备物中测定炎症/溶骨性级联反应的关键指标。

DESCRIPTION (provided by applicant): Intervertebral total disc replacement (TOR) implants potentially herald a paradigm shift in the management of degenerative disc disease. Preservation of motion may avoid adjacent-segment degeneration, a well-recognized complication effusion. Based on encouraging experience in Europe and now-concluding IDE trials, FDA approval is likely in early/mid 2005 for two leading designs: Charite III and ProDisc. As an alternative to fusion (approximately 330,000/year in the U.S.), an onrush of implantations of these devices seems imminent. The potential for late wear-related complications is concerning. Both devices involve metal-on-conventional-polyethylene bearings, and the TDR patient population is a decade younger than for THR/TKR. Moreover, owing to close proximity of the spinal cord, the potential consequences of implant failure are much more dire than for THR/TKR. It is crucial that the scientific community expeditiously confront the issue of TDR wear. A Bioengineering Research Partnership is proposed to provide a firm scientific basis for identifying and dealing with wear-related problems in TDR. Aim 1 is to develop techniques for TDR wear assessment in the pre-clinical phase. This will be done leveraging complementary numerical and physical techniques: sliding-distance-coupled finite element analysis (Iowa) and servo-controlled laboratory simulation (Leeds). Aim 2 is to implement a novel approach to in vivo TDR radiographic wear measurement (Iowa), using high-resolution digital image analysis to assess relative three-dimensional pose position of the implant's metallic end plates. After documenting accuracy/precision, the pose image analysis technique will be used to measure wear in one of the largest/longest-ongoing European TDR series (Munich). Aim 3 is to assess the functional biologic activity of TDR wear debris (Leeds). Morphologically realistic simulator-generated debris will be used to challenge cells in a culture preparation specifically tailored to reflect the local spinal environment, from which key metrics of the inflammatory/osteolytic cascade will be assayed.