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能会阻碍许多与高级关节面材料（如高交联聚乙烯）相关的磨损率改善。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使其在很大程度上局限于模糊的猜想领域。因此，试图减少第三体的发生和/或研究其对植入物性能的影响是零星的、异质的，并且通常在临床现实中的基础是可疑的。基于一系列最近的研究，这些研究有助于澄清第三身体挑战，植入物表面损伤和磨损率加速之间的机制，现在提出了两个新的转化研究方向。其中第一个方向是量化THA植入手术主要术中程序步骤的第三代身体生成倾向。这些数据应该有助于突出特定程序阶段的相对复杂性，这是构思和记录有效技术改进的必要初始步骤。第二个研究方向是建立一个临床基础的框架，为实验室第三方身体磨损测试制定一个可行的共识协议。为了获得广泛的认可，这种方案需要涉及可可靠量化的第三方挑战，导致临床上真实的对立面损伤。并且，它需要能够在临床现实范围内可再现地提供磨损率加速，理想情况下具有单调的机械接地剂量/响应关系。拟议的工作将涉及爱荷华州大学、利兹大学和俄亥俄州州立大学的研究小组之间的跨学科合作。将在患者手术和尸体准备过程中的术中不同阶段获得假体周围组织和液体样本，从这些样本中分离第三体碎片并进行定量分析。将扩展第三个身体诱发磨损率加速的计算模型，以解释形态学上可识别的股骨头划痕损伤，并直接进行物理确认。将使用新型三维激光显微测量法对记录有第三次身体挑战的结构中的回收股骨头上的划痕损伤进行登记，为记录临床代表性划痕损伤方案和严重度范围提供客观依据。将完善实验室方案，以通过聚乙烯嵌入的第三体碎屑产生（注册一致）股骨头划痕，然后将受损股骨头应用于标准化实验室磨损测试。在拟定工作结束时，我们希望能够确定THA手术植入的哪些步骤在第三个身体碎片生成方面最有问题。而且，我们希望已经开发出一个机械接地协议的实验室模拟第三机构磨损率加速，适合作为一个概念平台的共识测试标准。

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.