25,000 follow-up operations (revision operations) per year on the hip are due to implant failure (Figure 1). In 55% of the cases, aseptic implant loosening is the cause. Implant wear particles are considered to be a possible trigger. In some patients, these particles lead to an inflammatory reaction, later to bone loss (osteolysis) and thus to progressive implant loosening. Patient-specific factors thus also play an important role in the development of aseptic implant loosening.
In subproject A02, cell-based mechanisms that lead to aseptic implant loosening are therefore to be determined, taking into account patient-specific, molecular markers. In the future, this will enable countermeasures to be initiated before follow-up surgery becomes necessary.
To test whether aseptic loosening is associated with altered cellular composition and functionality of cell types, patient material obtained during surgery is collected from two cohorts: primary and follow-up implantations. Cells will be analyzed by RNA sequencing and flow cytometry, and intact tissue will be analyzed by histological staining of tissue sections (Figure 2). A two- or three-dimensional culture model with the patient’s own cells will be established to investigate the effect of wear particles from the implant on the surrounding tissue. The planned studies will also serve to answer the question to what extent cellular senescence (a mechanism of cell ageing) contributes to aseptic loosening, which could lead to an immediate therapeutic approach (senolysis).