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Supraphysiologic Fluid Shear Stress as an Alternative Cause of Short-term Aseptic Loosening in Total Knee Replacements

超生理流体剪切应力是全膝关节置换术中短期无菌性松动的另一个原因

基本信息

批准号：
9312214
负责人：
Karen I Cyndari
金额：
$ 4.9万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9312214
关键词：
Address Affect Arthritis Autopsy Biological Factors Biology Bone Resorption Cell Count Cell Line Cells Client satisfaction Clinical Coculture Techniques Complement Complex Degenerative polyarthritis Deposition Devices Disease Economic Burden Environment Failure Funding Gene Expression Gene Targeting Goals Human Implant In Vitro Investigation Joints Knee Knowledge Link Liquid substance Location Marrow Mechanics Mediating Medicare Minerals Modality Morbidity - disease rate Operative Surgical Procedures Osteoblasts Osteoclasts Osteolysis Pain Patients Physiological Polarization Microscopy Polyethylenes Procedures Process Pump Replacement Arthroplasty Research Retrieval Services Surface Synovial Fluid System Testing Thinness Time United States Work base bone bone loss cost economic cost experience experimental study fluid flow improved in vitro activity joint loading joint mobilization knee pain knee replacement arthroplasty migration particle premature prevent public health relevance response sample fixation shear stress standard of care substantia spongiosa success

项目摘要

DESCRIPTION (provided by applicant): Cemented Total Knee Replacement (TKR) is an established and reliable procedure that seeks to restore joint mobility and relieve pain associated with rheumatoid or osteo-arthritis. While over 600,000 knees are implanted with great success annually, a substantial portion (~15%) fail prematurely. Most long-term failures are due to a process known as aseptic loosening, where the mechanical interlock between trabecular bone and cement weakens due to the erosion (osteolysis) of bone. This allows the implant to migrate and become painful, necessitating a revision surgery. Aseptic loosening is most often attributed to osteolysis caused by the body's response to articulating surface polyethylene (PE) wear accumulation at the implant-bone interface. Importantly, short-term failures can and do occur, and these may not be related to PE debris since the amount of debris created is proportional to time in service. Recent studies of postmortem retrieved, clinically- successful, human TKRs point to an additional, contributing factor in aseptic loosening: in the short-term, there is >50% resorption of the trabeculae that initially interlock with the bone cement, but this occurs without much wear to the PE articulating surface. This suggests early loss of fixation is caused by an alternate mechanism. In the postmortem studies, it was observed that when joint loads are applied to the TKRs, synovial fluid and/or marrow is pumped through small gaps between the interlocked trabeculae and cement. The fluid shear stresses (FSS) generated from the fluid pumping is estimated to be supraphysiologic, and will likely have an effect on the osteoblasts and osteoclasts that line the surface of trabecular bone. The overall goal of this study is to show that these supraphysiologic fluid shear stresses are sufficient to cause resorption of the trabeculae that interlock with cement, and that this can occur without PE debris. The Specific Aims of this project are to show: 1) trabecular resorption at the interface occurs in the absence of PE debris, 2) supraphysiologic FSS can affect resorption by increasing osteoclast activity (mineral resorption) while decreasing osteoblast activity (mineral deposition), and 3) PE debris accumulation and supraphysiologic FSS act in concert to produce more resorption than either process alone. We will first identify the location and amount of PE debris at the cement-bone in postmortem retrieved, clinically successful, human tibial components of TKA with short term (<5 years) and long term (>10 years) use. We expect short-term devices to contain little to no wear at the interface, but have extensive bone resorption. In contrast, we expect long-term devices to have both substantial PE wear and resorption. Next, we will elucidate the effects of FSS ranging from sub to supraphysiologic levels on in vitro cell lines of osteoclasts and osteoblasts, with or without PE debris. These experiments will allow us to first, quantify PE debris in direct, physical relation to the cement-trabeculae interface of retrievals, and second, differentiate the effects of high FSS from PE debris. Overall, the goal of this work is to extend the long-term success of TKRs.