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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的该提案的目标是将尤卡坦小型猪建立为创新型临床前动物模型旨在治疗与韧带损伤相关的腕骨病变的治疗方法和关节成形术严重的骨关节炎 (OA) 很常见，通常会导致活动时出现腕部疼痛。最终，手腕置换术是唯一能够保留的治疗方法。然而，腕关节置换术后的结果。腕部骨关节炎的治疗效果比髋部、膝部或肩部的治疗差得多。进化速度比这些较大的关节慢得多，这在很大程度上是由于缺乏研究和可用数据。手腕的复杂性也带来了重大挑战，而且由于缺乏经过验证的临床前研究，情况变得更加复杂。动物模型可用于询问腕骨不稳定的后果并评估腕骨不稳定的能力腕骨置换术可恢复腕骨功能并限制临床前大型骨关节炎的进展。动物模型对于关节成形术装置的开发、转化和 FDA 批准至关重要随着老年人口的老龄化和活动量的增加，对髋部、膝盖和脊柱的需求也越来越大。因此，退行性腕部病变的治疗方法正在迅速增长，该提案的目标是将尤卡坦小型猪建立为腕骨治疗和关节成形术的模型，旨在治疗严重的骨关节炎将通过两个独立的目标来实现。使用建立的小型猪腕骨的生物力学和桡骨腕骨（RCB）的运动学在第二步中，我们将评估诱导腕骨后的体内 OA 进展。不稳定和腕骨半关节置换术治疗后，这两个目标都会出现三种腕部状况。以完整的腕骨为参考进行评估：桡骨中间韧带的分割（RIL组）， RIL+腕间背侧韧带分割术（RIL+DIC组）和桡骨腕骨人工半髋关节置换术（RCBH 组）目标 1 的结果测量将包括腕部生物力学和桡骨腕骨。目标 2 的结果测量将包括步态和软骨的时空测量。在 R21 项目结束时，我们将首次全面描述健康问题。猪腕骨的生物力学，我们将建立一种新型的腕骨动物模型该项目将通过半关节成形术和创新疗法来推进腕骨不稳定性的治疗。提供适合目的的动物模型，能够评估创新疗法和疗法的重要特征关节成形术设计（例如形状、材料、表面处理、承载表面、固定方法、骨/软组织向内生长和磨损碎片），以及广泛的未来创新疗法，例如组织工程韧带、软骨和骨软骨移植物以及患者特定的 3D 打印植入物。