In vivo chemical changes of contemporary polyethylene in TKA: implications for wear and osteolysis - This proposal addresses the unmet need that the mechanisms governing in vivo chemical changes of total knee arthroplasty (TKA) tibial liners are not known. Our objective is to determine the in vivo chemical alteration processes of contemporary ultra-high molecular weight polyethylene (PE) tibial liners, their impact on mechanical and wear behavior, and enhance preclinical methods to predict particle-induced osteolysis in TKA. The proposed work is significant because understanding how PE changes in the body is essential to understand long-term PE degradation processes and open new pathways for technology to maximize implant longevity. This research marks an essential step toward our long-term goal of achieving a lifetime TKA— independent of patient age. Our central hypothesis is that initial PE structure, implant design, and the chemical periprosthetic environment drive in vivo oxidation, mechanical properties, wear, and thereby the onset of osteolysis. We base our hypothesis and approach on our preliminary data of TKA wear assessment, validated FEA-based wear simulation, chemical and mechanical characterization of PE, and FTIR imaging (FTIR-I) augmented histopathological analysis. We will test our hypothesis with three Specific Aims. Aim 1. To determine PE mechanical in vivo changes and their impact on TKA long-term wear behavior and damage progression. Working Hypothesis: The initial PE structure and tibial liner design drive the rate, quantity, and spatial distribution of in vivo mechanical properties changes. We will test the hypothesis using retrieval analysis, bench tests, and FEA which simulates tibial liner wear and damage after oxidation-induced mechanical properties changes. Aim 2. To determine the onset and progression of late osteolysis in contemporary TKA in a large retrieval cohort by means of FTIR-I augmented histopathological evaluation. Working hypothesis: osteolysis onset and progression will be prevalent in otherwise well-functioning TKAs as seen by radiolucencies and FTIR-I augmented histopathological markers within periprosthetic tissue at 12-15 years in situ. Aim 3. To determine PE chemical in vivo changes and the impact of the local periprosthetic environment. Working hypothesis: Competitive absorption of pro-/anti-oxidative constituents from the periprosthetic environment accelerates PE oxidation and changes in mechanical/tribological properties. A novel FEA model will be used to simulate competitive absorption, verified with FTIR-I/Raman scans of retrieved liners. The proposed research is innovative because it focuses on the relationship between oxidation, in vivo exposure of tibial liners to pro- and anti-oxidative species, in vivo loading, and the relationship to PE type (dose and thermal treatment). It will also investigate new techniques for identifying PE within periprosthetic tissues. This new and substantively different approach will open new horizons to minimize in vivo PE oxidation, diagnose PE-induced inflammatory responses, and predict implant longevity.