Doctor of Philosophy
Musculoskeletal Health Research
Holdsworth, David W
Joint replacement is an increasingly common surgery with over 130,000 procedures performed annually in Canada. Although joint replacement surgery is highly successful, implants do not last a lifetime, and often have to be replaced via costly revision surgeries. Before innovations aimed at extending the life of implants are applied to the clinic, testing must be performed in animal models. Clinically representative small-animal models of joint replacement would be ideal in the initial stages of research and development, due to ease of handling and low costs, but few such models have been established in the literature. Thus, we describe the development of a clinically representative rat model of hip hemiarthroplasty.
A database of micro-computed tomography volumes of skeletally mature male Sprague-Dawley rats was analyzed to quantify the dimensions of the proximal rat femur. This was done in order to guide the creation of a parameterized rat-hip implant in computer-aided design software. Sets of rat-specific femoral implants were then produced in medical-grade alloys using additive manufacturing. Implants were then installed into cadaveric, and then live rats. Micro-computed tomography imaging was used to evaluate the position of the implant within the proximal femur longitudinally. Animals also underwent a gait analysis protocol using a commercially available CatWalk XT system, in parallel with an X-ray fluoroscopy protocol, whereby animals were imaged while running on a custom made radiolucent treadmill.
Surgeries were successful in live animals; rats were able to tolerate the procedure and were observed ambulating on their affected limbs immediately following recovery from anaesthesia. Micro-CT imaging revealed clinically representative complications (implant subsidence) in some animals that mimic complications found in larger models. Functionally loaded implants were observed in the remaining animals at twelve weeks, postoperative. Rats were successful in completing gait analysis protocols on both the Catwalk and fluoroscopic treadmill systems. Animal gait was restored following hemiarthroplasty.
We report the first clinically representative rat hip hemiarthroplasty surgeries using custom 3D-printed metal implants. This thesis supports the feasibility of this model as a preclinical platform for basic scientists to study osseointegration, metal-on-cartilage interactions, and joint infection around a functional implant.
Summary for Lay Audience
Joint replacement surgery is an increasingly common procedure, performed to relieve the pain of cartilage damage caused by osteoarthritis, or to restore joint function following a traumatic injury. While joint replacement surgery is highly successful, implants don’t always last a lifetime. When implants fail to function properly, they must be replaced via revision surgeries; these procedures are higher-risk, more complex and more costly compared to initial joint replacement surgeries, and therefore are to be avoided or delayed if possible. Consequently, scientists continue to research new ways to extend the life of implants, and reduce the burden of revision surgeries. However, before new innovations can be applied to the clinic, testing in animal models is often required. Historically, large animals (such as sheep) have been used to test joint implants, but these trials are expensive to conduct, and there are sometimes ethics concerns of testing in more sentient species. Small lab animals are more readily available, but joint implants are not easily manufactured in the sizes required for small animal testing. In this thesis we describe an approach to create custom small-animal implants, through the use of image-based design and 3D-metal printing. We also demonstrate the installation of these implants in rats, followed by 3D imaging and analysis of animals walking after surgery. Our rat hip implant model presents a new research tool for scientists who are looking to find ways to extend the life of implants, so that patients can maintain lifelong mobility with fewer surgical interventions.
Paish, Adam DM, "A Clinically Representative Rat Model of Hip Hemiarthroplasty" (2020). Electronic Thesis and Dissertation Repository. 7264.
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Available for download on Thursday, September 01, 2022