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