Validation of the Yucatan Minipig as a Preclinical Model for Wrist Bone Arthroplasty

尤卡坦小型猪作为腕骨关节置换术临床前模型的验证

• 批准号: 10574928
• 负责人: Joseph J Crisco
• 金额: $ 18.04万
• 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: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10574928
• 关键词: 3-Dimensional; 3D Print; Acute; Aftercare; Aging; Animal Model; Arthritis; Articulation; Biological Products; Biological Response Modifier Therapy; Biomechanics; Bone Spur; Cartilage; Clinic; Clinical; Data; Degenerative polyarthritis; Development; Device or Instrument Development; Devices; Disease; Dorsal; Failure; Family suidae; Future; Gait; Goals; Growth; Health; Hip region structure; Human; Implant; In Vitro; Individual; Joints; Knee; Ligaments; Measurement; Measures; Methods; Miniature Swine; Modeling; Musculoskeletal; Older Population; Outcome; Outcome Measure; Pain; Pathology; Patients; Pre-Clinical Model; Protocols documentation; Radial; Randomized; Replacement Arthroplasty; Research; Resort; Robotics; Scaphoid bone; Severities; Shapes; Shoulder; Silicon; Study models; Surface; Survival Rate; Therapeutic; Thick; Time; Tissue Engineering; Translations; Validation; Vertebral column; Work; Wrist; aging population; biomechanical test; bone; carpus bone; design; improved; in vitro Model; in vivo; innovation; kinematics; ligament injury; manufacture; new technology; next generation; novel; novel therapeutics; osteochondral tissue; pre-clinical; primary outcome; sample fixation; secondary outcome; soft tissue; spatiotemporal; success; tool; wrist function

ABSTRACT The goal of this proposal is to establish the Yucatan minipig as a preclinical animal model for innovative therapeutics and arthroplasties designed to treat carpal bone pathologies associated with ligament injuries and severe osteoarthritis (OA). Degenerative and traumatic wrist pain is common, often resulting in activity restrictions and the inability to work. Ultimately, wrist replacement is the only treatment capable of retaining wrist function while counteracting the degenerative changes. However, outcomes after wrist arthroplasty treatment are much poorer than those for the hip, knee, or shoulder. Treatments for wrist osteoarthritis have evolved much more slowly than these larger joints, due in large part to the lack of study and available data. The wrist’s complexity also presents a significant challenge, compounded by the lack of a validated preclinical animal model that can be used to interrogate the consequences of carpal instability and evaluate the ability of carpal bone replacements to restore carpal function and limit osteoarthritis progression. Preclinical large animal models have been crucial for the development, translation, and FDA approval of arthroplasty devices for hips, knees, and spines. With an aging and increasingly active older population, the need for improved treatments for degenerative wrist pathologies is growing rapidly. Accordingly, the goal of this proposal is to establish the Yucatan minipig as a model for carpal bone therapeutics and arthroplasties that are designed to treat severe osteoarthritis. This goal will be achieved in two independent aims. In the first, we will quantify the biomechanics of the minipig carpus and the kinematics of the radial carpal bone (RCB) using established in vitro biomechanical testing. In the second, we will evaluate OA progression in vivo, after induced carpal instability and after treatment with a carpal bone hemiarthroplasty. In both aims three carpal conditions will be evaluated, with the intact carpus as a reference: division of the radial intermediate ligament (RIL group), division of the RIL+dorsal intercarpal ligament (RIL+DIC group), and hemiarthroplasty of the radial carpal bone (RCBH group). Outcome measures for Aim 1 will include wrist biomechanics and radial carpal bone kinematics. Outcome measures for Aim 2 will include spatiotemporal measurements of gait and cartilage health. At the conclusion of this R21 project, we will, for the first time, have fully characterized the biomechanics of the porcine carpus and we will have established a novel animal model for carpal bone hemiarthroplasty and innovative therapeutics. This project will advance the treatment of carpal instabilities by providing a fit-for-purpose animal model capable of evaluating important features of innovative treatments and arthroplasty designs (e.g., shape, material, finish, bearing surfaces, fixation methods, bone/soft tissue ingrowth, and wear debris), as well as the broad range of future innovative therapeutics, such as tissue engineered ligaments, cartilage and osteochondral grafts, and patient-specific 3D printed implants.

抽象的 该提议的目的是建立尤卡坦小米蒂皮作为创新的临床前动物模型 旨在治疗与韧带损伤和 严重的骨关​​节炎（OA）。退化性和创伤性手腕疼痛很常见，通常导致活动 限制和无法工作。最终，手腕替代是唯一能够保留的治疗方法 腕部功能在抵消退化性变化的同时。但是，手腕关节置换术后的结果 治疗比臀部，膝盖或肩膀的治疗要差得多。腕骨关节炎治疗 与这些较大的关节相比，进化的速度要慢得多，这在很大程度上是由于缺乏研究和可用数据。 手腕的复杂性也提出了一个重大挑战，这是由于缺乏经过验证的临床前的复杂性 动物模型，可用于询问腕骨不稳定性的后果并评估 腕骨替代物恢复腕部功能并限制骨关节炎的进展。临床前大 动物模型对于关节置换设备的开发，翻译和FDA批准至关重要 用于臀部，膝盖和刺。随着老龄化和日益活跃的老年人的需求 退化手腕病理的治疗迅速增长。彼此认为，该提议的目标是 建立Yucatan Minipig作为腕骨疗法和旨在的节肢动物的模型 治疗严重的骨关​​节炎。这个目标将在两个独立目标中实现。首先，我们将量化 Minipig Carpus的生物力学和径向腕骨（RCB）的运动学使用 体外生物力学测试。第二个，我们将在诱导腕骨后评估体内OA进展 不稳定性和用腕骨半截骨术治疗后。在这两个目标中，三个腕部条件将是 评估，完整的腕骨作为参考：径向中间韧带（RIL组）的分裂， RIL+背骨间韧带（RIL+DIC组）和径向腕骨半截骨术的分裂 （RCBH组）。目标1的结果指标将包括手腕生物力学和径向腕骨 运动学。目标2的结果指标将包括步态和软骨的时空测量 健康。在这个R21项目的结论中，我们将首次完全表征 猪腕的生物力学，我们将建立一个新型的腕骨动物模型 半截骨术和创新的治疗学。该项目将通过 提供一种适合用途的动物模型，能够评估创新治疗的重要特征和 关节置换术设计（例如形状，材料，饰面，轴承表面，固定方法，骨/软组织 碎屑和磨损碎片）以及多种未来创新的治疗剂，例如组织 工程韧带，软骨和骨软骨移植物以及患者特异性的3D印刷叶片。