Comprehensive Analysis of Determinants of Polyethylene Wear and the Related Tissue Response to Improve Outcomes in Total Hip Arthroplasty - The Cadepe-Tha Study

Approximately 10% of individuals in Western countries require total hip arthroplasty (THA) in their lifetime. The leading long-term cause of THA revision remains wear and wear particle induced inflammation. Although highly cross-linked polyethylene (HXLPE), today’s best choice for acetabular sockets, has mitigated mid-term wear issues, long-term concerns persist with variable clinical per-formance among products. Particularly, we have detected deviations from specifications that greatly influence the implant’s wear performance. Confidentiality of material properties and processing data limits analysis, and there is a lack of comparative studies correlating implant properties with clinical and histopathological outcomes. Wear particles from HXLPE are smaller and biologically more potent than those from conventional polyethylene and are often undetectable in routine histology, underscoring the need for innovative diagnostic methods. This project will characterize the in vitro and in vivo wear behaviour of polyethylene (PE) sockets from retrieved THA components, particularly HXLPE, to identify product-specific differences and their relation to failure modes and tissue response. Through collaboration with centres in Switzerland, Germany, Austria and the USA, we will analyse ~5’000 retrievals to ensure robust statistical power. Our central hypothesis is that structural and property differences among PE brands directly affect the in vivo wear performance, associated tissue response and ultimately medium- to long-term implant failure. We will test our hy-pothesis with the following work packages (WP): - WP1: Collect retrieved PE sockets from revision THA with corresponding periprosthetic tissue samples and clinical infor-mation. Retrievals and clinical data will be obtained from an international multicentre network of reference centres in revision THA. - WP2: Characterize the chemical structure and cross-linking degree of PE from all major THA brands and their impact on mechanical properties and wear resistance. Samples from the bulk of the material will be characterized using Fourier-transform infrared (FTIR) spectroscopy, mechanical testing, and tribological testing. - WP3: Precisely analyse the relationship between radiation exposure, radiation absorption, and the trans-vinylene index in HXLPE. Much-needed benchmarks for cross-linking by gamma- and by beta-irradiation will be established. - WP4: Determine in vivo wear rates for HXLPE bearings in THA and assess how wear volume and patterns relate to material design and clinical factors. Wear will be assessed from retrievals with an optical coordinate measuring machine. The impact of var-ious factors on in vivo wear will be assessed via multiple regression and novel artificial intelligence-based methods. - WP5: Characterize histopathological patterns associated with HXLPE wear in THA in relation to material design and clinical confounding factors. Histopathological analysis will be augmented by a novel FTIR imaging (FTIR-I) approach to identify and lo-cate intra-cellular wear debris. This project will characterize material properties and wear behaviour of revised THA components, offering a unique opportunity to determine with sufficient statistical power the determinants of PE wear in THA, particularly for HXLPE, integrating product specifici-ties as well as the corresponding tissue response. Benchmarks for material properties and processing will be established, improving implant development and failure analysis. A unique histopathological approach augmented by FTIR-I, currently available only at our collaborating institution in the USA, will be implemented in Switzerland, establishing an innovative reference centre in Europe. More cost-effective methods will be developed for broader application. Beyond improving patient-related outcomes, the findings may be expected to reduce medium- to long-term revision rates by ~50%, significantly alleviating the burden on healthcare systems.