Quantifying 3rd Body Challenge in Total Hip Arthroplasty

描述（由申请人提供）：当存在时，全关节置换术中的第三体效应可以避免许多磨损率的改善，否则与高级轴承材料（如高交联聚乙烯）相关。虽然长期以来被认为是一个潜在的临床问题，但不幸的是，量化第三体挑战的困难很大程度上局限于模糊猜想的领域。因此，减少第三体发生和/或研究其对植入物性能影响的尝试是零星的、异质的，并且在临床现实中往往存在问题。最近的一系列研究已经帮助阐明了连接第三体挑战、种植体表面损伤和磨损率加速的机制，现在提出了两个新的转化研究方向。第一个方向是量化THA植入术中主要手术步骤的第三体生成倾向。这些数据应有助于突出具体程序阶段的相对危害性，这是构思和记录有效技术改进的必要初步步骤。第二个研究方向是为实验室第三体磨损测试建立一个切实可行的共识协议的临床基础框架。为了获得广泛的接受，这样的方案将需要涉及一个可靠的可量化的第三体挑战，该挑战会导致临床现实的反面损伤。此外，它还需要能够在临床实际的范围内再现磨损率加速度，理想情况下是具有单调的、机械接地的剂量/反应关系。拟议的工作将涉及爱荷华大学、利兹大学和俄亥俄州立大学的研究小组之间的跨学科合作。将在患者手术、术中各个阶段和尸体准备过程中获取假体周围组织和液体标本，从中分离出第三体碎片标本并进行定量分析。将扩展第三体诱导磨损率加速度的计算模型，以考虑形态可识别的股骨头划伤，并进行直接物理验证。我们将使用新型三维激光显微测量技术，对记录有第三体冲击的构造体中取回股骨头的划伤损伤进行登记，为记录具有临床代表性的划伤损伤方案和严重程度范围提供客观基础。将完善实验室方案，以从嵌入聚乙烯的第3具尸体碎片中产生（与注册表一致的）股骨头划痕，然后将损坏的头部用于标准化实验室磨损测试。在这项工作的结论中，我们希望能够确定THA手术植入的哪些步骤在第三体碎片产生方面是最有问题的。而且，我们希望开发出一种机械接地的方案，用于第三体磨损率加速的实验室模拟，适合作为共识测试标准的概念平台。

DESCRIPTION (provided by applicant): When present, 3rd body effects in total joint replacement can obviate many of the wear rate improvements otherwise associated with advanced bearing materials such as highly cross-linked polyethylenes. While long recognized as a potential clinical concern, the difficulties of quantifying 3rd body challenge unfortunately have kept it largely confined to the domain of nebulous conjecture. Consequently, attempts to reduce the genesis of 3rd bodies and/or to study their effects on implant performance have been sporadic, heterogeneous, and often of questionable grounding in clinical realism. Building on a series of recent studies which have helped clarify the mechanisms linking 3rd body challenge, implant surface damage, and wear rate acceleration, two new directions of translational research are now proposed. The first of these directions is to quantify the 3rd body generation propensity of major intra-operative procedural steps of THA implantation surgery. Such data should be helpful to highlight the relative deleteriousness of specific procedural stages, a necessary initial step toward conceiving and documenting effective technical improvements. The second research direction is to establish a clinically-grounded framework for a practicable consensus protocol for laboratory 3rd body wear testing. To gain widespread acceptance, such a protocol will need to involve a reliably quantifiable 3rd body challenge that causes clinically realistic counterface damage. And, it will need to have the ability to reproducibly deliver wear rate accelerations in a clinically realistic range, ideally with a monotonic, mechanistically-grounded dose/response relationship. The proposed work will involve interdisciplinary collaboration among research groups at the University of Iowa, the University of Leeds, and Ohio State University. Peri-prosthetic tissue and fluid specimens will be obtained at various stages intra-operatively during patient surgeries and in cadaver preparations, from which specimens the 3rd body debris will be isolated and quantitatively analyzed. Computational models of 3rd body-induced wear rate acceleration will be extended to account for morphologically identifiable femoral head scratch damage, with direct validation physically. A registry of scratch damage on retrieval femoral heads in constructs with documented 3rd body challenge will be compiled using novel 3-dimensional laser micrometry, providing an objective basis to document clinically representative scratch damage regimens, and ranges of severity. A laboratory protocol will be refined to generate (registry-consistent) femoral head scratching from polyethylene-embedded 3rd body debris, with the damaged heads then being applied in standardized laboratory wear testing. At the conclusion of the proposed work, we expect to have identified which steps of THA surgical implantation are most problematic in terms of 3rd body debris generation. And, we expect to have developed a mechanistically-grounded protocol for laboratory simulation of 3rd body wear rate acceleration, suitable as a conceptual platform for a consensus testing standard.