Biological activity of metallic wear particles and metal ions in vitro and in vivo

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The aseptic loosening is still the most common reason for revision surgery in total joint arthroplasty and is mainly caused by a tissue response to wear particles. The proposed project seeks to determine a difference of the biologic activity to wear particles of hip endoprostheses between common metal-metal or ceramic-polyethylene bearing surfaces both in vitro and in vivo. For these experiments, wear particles of ceramic-polyethylene and metal-metal bearing surfaces are produced in a wear simulator. The generated wear particles (metal and polyethylene wear particles) are analyzed and categorized regarding size and shape parameters. After purification and elimination of adherent endotoxin, the generated wear particles (polyethylene, metal, and metal ions) are cultured with different human cell types (monocytes, macrophages, osteoblasts), comparing them with metal ions, as a result of corrosion processes.The focus of the in vitro studies is the analysis of cell and molecular biological effects depending on the material type and topography of the wear particles. The vitality and proliferation of human primary osteoblasts and macrophages, as well as the rate of apoptosis or necrosis, after contact with the wear particles should be determined. In addition, a quantification of activated cytokines and the expression of OPG and sRANKL after contact with the particles will be evaluated.In a second step, the abrasive particles are used after elimination of adherent lipopolysaccharides in an established animal model. The particles are injected into murine knee joints to analyze the systemic inflammatory reactions in the synovial tissue using intravital microscopy. In addition, the local and systemic inflammatory reactions are evaluated using histological investigations and immunohistochemistry, and compared to the in vitro results.Hence, a basic understanding of this inflammatory reaction to the applied wear particles and metal ions can be achieved. Since the time course of immune responses to the wear debris is unclear so far, in a subsequent project period the various wear particles and metal ions should be evaluated for their biological activity at different times.The project findings can be incorporated into the development of new strategies for the prevention of particle-induced aseptic loosening of total joint replacements such as new developments in material and surface design and medical treatment approaches for blocking inflammatory signal pathways.