Advancing Hemiarthroplasty: Predicting in vivo performance of cartilage bearing systems through benchtop and ex vivo testing.

推进半关节成形术：通过台式和离体测试预测软骨支撑系统的体内性能。

• 批准号: 10719393
• 负责人: Joseph J Crisco
• 金额: $ 73.05万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719393
• 关键词: Acceleration; Alloys; Animal Model; Articulation; Biocompatible Materials; Biological Assay; Bone Spur; Bovine Cartilage; Cartilage; Cartilage Matrix; Cell Survival; Cells; Ceramics; Characteristics; Chromium; Cobalt; Consensus; Data; Degenerative Disorder; Degenerative polyarthritis; Development; Disease; Distal; Equation; Failure; Family suidae; Future; Gait; Glycosaminoglycans; Goals; Hardness; Harvest; Health; Hip region structure; Histopathology; Hydroxyproline; Individual; Ions; Joints; Knee; Life; Linear Models; Materials Testing; Measures; Mechanics; Metabolism; Metals; Methodology; Microscopic; Miniature Swine; Modeling; Modulus; Molybdenum; Motion; Osteogenesis; Outcome; Outcome Measure; Patients; Performance; Polymers; Preclinical Testing; Proteoglycan; Proxy; Replacement Arthroplasty; Reporting; Research; Roentgen Rays; Sampling; Shoulder; Standardization; Statistical Models; Surface; Synovitis; System; Testing; Thick; Tissues; Titanium; Toxic effect; Wettability; Work; Wrist; bone; cell injury; cortical bone; design; foot; improved; in vivo; joint destruction; mechanical properties; novel; outcome prediction; performance tests; porcine model; predicting response; preservation; primary outcome; programs; pyrolytic carbon; response; secondary outcome; spatiotemporal; success; tool

ABSTRACT The ultimate goal of this research program is to advance hemiarthroplasty performance. Hemiarthroplasty involves replacement of one of the articular joint surfaces with an artificial bearing surface. It offers a clear benefit in patients with localized cartilage damage, preserving the healthy bone and cartilage in the joint to maximize future treatment options. And hemiarthroplasty is inherent in the replacement of individually diseased carpal (wrist) or tarsal (foot) bones, which have multiple articulations with neighboring bones. Currently, hemiarthroplasty outcomes vary dramatically by the joint involved and by the type of bearing surface used to articulate with the opposing cartilage. Failure most often occurs by degeneration of the opposing articular surface. A critical challenge in advancing hemiarthroplasty performance is the ability to identify bearing surfaces that will maintain healthy cartilage. There are numerous candidate biomaterials that might be suitable for use as hemiarthroplasty bearing surfaces, including metals, ceramics, and polymers, as well as specialized coatings, such as titanium nitride and pyrolytic carbon. However, the performance of these materials has been mixed, due in large part to the lack of standardized and validated testing methodologies. Accordingly, the specific objective of this project is to develop a model where benchtop and ex vivo testing can predict the cartilage response to hemiarthroplasty bearing system wear in a fit-for-purpose large animal model. This goal will be achieved by completing three specific aims. In the first, we will characterize the material and mechanical properties of eight candidate hemiarthroplasty bearing surfaces (2 metals, 4 polymers, 1 ceramic, and 1 pyrolytic carbon) using standard benchtop mechanical tests (roughness, wettability, modulus, hardness, and wear testing against cortical bone). In the second, we will characterize the cartilage bearing performance of each of the candidate biomaterials by wear testing them against bovine cartilage plugs in a joint motion-simulating biotribometer, using proteoglycan/glycosaminoglycan (PG/GAG) and hydroxyproline as measures of cartilage matrix degradation and live/dead assays as a measure of cell damage. In the third, we will test four of the 8 materials from Aims 1 & 2 as bearing surfaces in a novel unicompartmental tibial hemiarthroplasty model in the Yucatan minipig, measuring cartilage damage (macro- and microscopic), synovial inflammation, cartilage thickness, and osteophyte bone formation at 52 weeks. And finally, we will develop a statistical model where the data from Aims 1 and 2 can be used to predict the outcome in Aim 3. The work outlined in this proposal will yield a model where benchtop and ex vivo testing can predict the cartilage response to hemiarthroplasty. This project will provide a crucial tool needed to accelerate the design, development, and FDA clearance of new hemiarthroplasty bearing surfaces, resulting in a significant benefit for millions of patients afflicted with degenerative joint disease.

抽象的 该研究计划的最终目标是提高半关节置换术的性能。半关节置换术 涉及用人造轴承表面替换其中一个关节表面。它提供了明显的好处 对于局部软骨损伤的患者，保留关节中的健康骨骼和软骨，以最大限度地发挥作用 未来的治疗选择。半关节置换术是替换个别患病腕骨所固有的 （手腕）或跗骨（足）骨，与邻近的骨头有多个关节。现在， 半关节置换术的结果因所涉及的关节以及用于支撑的支撑表面的类型而有很大差异 与相对的软骨形成关节。失败最常见的原因是对侧关节退化 表面。提高半关节置换术性能的一个关键挑战是识别支撑表面的能力 这将保持健康的软骨。有许多候选生物材料可能适合用作 半关节成形术轴承表面，包括金属、陶瓷和聚合物，以及专门的涂层， 例如氮化钛和热解碳。然而，这些材料的性能参差不齐，因为 很大程度上是由于缺乏标准化和经过验证的测试方法。据此，具体目标 该项目的目的是开发一个模型，通过台式和离体测试可以预测软骨反应 半关节成形术轴承系统在适合用途的大型动物模型中的磨损。这一目标将通过以下方式实现 完成三个具体目标。首先，我们将表征八种材料的材料和机械性能 候选半关节成形术轴承表面（2 种金属、4 种聚合物、1 种陶瓷和 1 种热解碳） 标准台式机械测试（粗糙度、润湿性、模量、硬度和磨损测试） 皮质骨）。在第二部分中，我们将描述每个候选者的软骨承载性能 通过在关节运动模拟生物摩擦计中对牛软骨塞进行磨损测试，使用 蛋白聚糖/糖胺聚糖 (PG/GAG) 和羟脯氨酸作为软骨基质降解和 活/死测定作为细胞损伤的衡量标准。在第三部分中，我们将测试目标 1 和 2 中的 8 种材料中的四种 作为尤卡坦半岛小型猪新型单间室胫骨半关节置换术模型中的支撑面，测量 软骨损伤（宏观和微观）、滑膜炎症、软骨厚度和骨赘 52周形成。最后，我们将开发一个统计模型，其中目标 1 和 2 的数据可以 用于预测目标 3 的结果。本提案中概述的工作将产生一个模型，其中台式和 离体测试可以预测软骨对半关节置换术的反应。该项目将提供一个重要的工具 需要加速新的半关节置换术轴承表面的设计、开发和 FDA 批准， 为数百万患有退行性关节疾病的患者带来了显着的益处。