Wear Analysis of Intervertebral Total Disc Replacements

描述（由申请人提供）：椎间全椎间盘置换术（TOR）植入物可能预示着退行性椎间盘疾病治疗的范式转变。保持运动可避免邻近节段退变，这是一种公认的并发症。基于欧洲令人鼓舞的经验和目前正在结束的IDE试验，FDA可能在2005年初/中期批准两个主要设计：Charite III和ProDisc。作为融合的替代方案（在美国每年大约有33万例），这些装置的植入似乎迫在眉睫。后期磨损相关并发症的可能性令人担忧。这两种设备都采用金属-非常规聚乙烯轴承，TDR患者比THR/TKR患者年轻10岁。此外，由于靠近脊髓，植入物失败的潜在后果比THR/TKR要严重得多。至关重要的是，科学界必须迅速面对TDR磨损问题。建议建立生物工程研究伙伴关系，为查明和处理TDR中与磨损有关的问题提供坚实的科学基础。目标1是在临床前阶段开发TDR磨损评估技术。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是实现一种新的方法，用于体内TDR射线磨损测量（Iowa），使用高分辨率数字图像分析来评估种植体金属端板的相对三维姿态位置。在记录准确性/精度之后，姿态图像分析技术将用于测量最大/持续时间最长的欧洲TDR系列之一（慕尼黑）的磨损。目的3是评估TDR磨损碎片的功能性生物活性（利兹）。形态学上逼真的模拟器生成的碎片将用于挑战培养制剂中的细胞，该培养制剂专门用于反映局部脊柱环境，从中将分析炎症/溶骨级联的关键指标。

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.