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.

摘要 该提案的目标是建立尤卡坦小型猪作为创新的临床前动物模型。 设计用于治疗与韧带损伤相关的腕骨病变的治疗和关节成形术， 严重骨关节炎（OA）。退行性和创伤性腕关节疼痛是常见的，往往导致活动 限制和无法工作。最终，腕关节置换术是唯一能够保留 手腕的功能，同时抵消退行性变化。然而，腕关节成形术后的结果 治疗比髋关节、膝关节或肩关节差得多。腕关节骨关节炎的治疗方法有 进化比这些大关节慢得多，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的挑战，由于缺乏有效的临床前研究， 动物模型，可用于询问腕关节不稳定的后果和评估的能力， 腕骨置换术，以恢复腕关节功能并限制骨关节炎的进展。临床前大型 动物模型对于关节成形术器械的开发、转化和FDA批准至关重要 用于臀部膝盖和脊柱随着老龄化和日益活跃的老年人口，需要改善 对退化性腕部病变的治疗正在迅速发展。因此，本提案的目标是 建立尤卡坦小型猪作为腕骨治疗和关节成形术的模型， 治疗严重的骨关节炎。这一目标将通过两个独立的目标来实现。首先，我们将量化 生物力学的小型猪腕骨和桡侧腕骨（RCB）的运动学，使用建立在 体外生物力学测试。第二，我们将在体内评估OA进展，诱导腕关节后， 不稳定和治疗后的腕骨半关节成形术。在这两个目标三腕条件将是 以完整的腕骨为参照：桡侧中间韧带分离（RIL组）， 分离RIL+腕背侧韧带（RIL+DIC组）和桡侧腕骨半关节成形术 (RCBH组）。目标1的结局指标将包括腕部生物力学和桡侧腕骨 运动学目标2的结局指标将包括步态和软骨的时空测量 健康在这个R21项目结束时，我们将第一次全面描述 猪腕骨的生物力学，我们将建立一个新的动物模型，腕骨 半关节成形术和创新疗法。该项目将推进腕关节不稳定的治疗， 提供能够评估创新治疗的重要特征的适用动物模型， 关节成形术设计（例如，形状、材料、光洁度、关节面、固定方法、骨/软组织 向内生长和磨损碎屑），以及广泛的未来创新疗法，如组织 工程韧带，软骨和骨软骨移植物，以及患者特定的3D打印植入物。