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

摘要 这项建议的目标是建立尤卡坦小型猪作为创新的临床前动物模型 治疗和关节成形术旨在治疗与韧带损伤相关的腕骨病理和 严重骨关节炎(OA)。退行性和创伤性手腕疼痛很常见，通常会导致活动。 限制和无法工作。归根结底，手腕置换是唯一能够保留 腕关节功能，同时对抗退行性变化。然而，腕关节置换术后的结果 治疗要比臀部、膝盖或肩部的治疗差得多。手腕骨关节炎的治疗方法有 这在很大程度上是由于缺乏研究和可用的数据，比这些更大的关节进化得更慢。 手腕的复杂性也是一个重大的挑战，加上缺乏经过验证的临床前 动物模型，可用于询问腕关节不稳定的后果和评估能力 腕骨置换可恢复腕关节功能并限制骨关节炎的进展。临床前大型 动物模型对于关节置换设备的开发、转换和FDA的批准至关重要 用于臀部、膝盖和脊椎。随着老龄化和日益活跃的老年人口，需要改善 腕关节退行性病变的治疗方法正在迅速发展。因此，这项提案的目标是 建立尤卡坦小型猪作为腕骨治疗和关节成形术的模型，旨在 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 建立的小型猪腕骨生物力学和桡腕骨运动学研究 体外生物力学测试。在第二项研究中，我们将评估在体腕骨诱导后的骨性关节炎进展。 不稳定和腕骨半关节置换术治疗后。在这两个目标中，三个腕部状况将是 以完整的腕骨为参照进行评估：分离桡骨中间韧带(RIL组)， RIL+腕间背侧韧带分离(RIL+DIC组)和桡腕骨半关节置换术 (RCBH组)。AIM 1的结果测量将包括腕部生物力学和桡腕骨 运动学。目标2的结果测量将包括步态和软骨的时空测量 健康。在这个R21项目结束时，我们将第一次充分描述 我们将建立一种新型的腕骨动物模型。 半关节置换术和创新疗法。该项目将通过以下方式推进腕关节不稳定的治疗 提供适合目的的动物模型，能够评估创新治疗的重要特征和 关节成形术设计(例如形状、材料、表面光洁度、承重面、固定方法、骨/软组织 内生和磨损碎片)，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，以及患者特定的3D打印植入物。

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.