1. Center for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse, Heidelberg, Germany.
2. Department of Anesthesiology, Heidelberg University Hospital, Heidelberg.
3. Laboratory of Biomechanics and Implant Research, Center for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg, Germany.
4. Institute of Immunology, Heidelberg University. Heidelberg, Germany.
5. Institute of Pathology, Universitätsmedizin der Johannes Gutenberg Universität Mainz, Germany.
Background: Implant loosening - either infectious or aseptic- is a still a major complication in the field of orthopaedic surgery. In both cases, a pro-inflammatory peri-prosthetic environment is generated by the immune system - either triggered by bacteria or by implant wear particles - which leads to osteoclast differentiation and osteolysis. Since infectious cases in particular often require multiple revision surgeries, we wondered whether commonly used surgical suture material may also activate the immune system and thus contribute to loss of bone substance by generation of osteoclasts.
Methods: Tissue samples from patients suffering from infectious implant loosening were collected intraoperatively and presence of osteoclasts was evaluated by histopathology and immunohistochemistry. Further on, human monocytes were isolated from peripheral blood and stimulated with surgical suture material. Cell supernatant samples were collected and ELISA analysis for the pro-inflammatory cytokine IL-8 was performed. These experiments were additionally carried out on ivory slices to demonstrate functionality of osteoclasts. Whole blood samples were incubated with surgical suture material and up-regulation of activation-associated cell surface markers CD11b and CD66b on neutrophils was evaluated by flow cytofluorometry analysis.
Results: We were able to demonstrate that multinucleated giant cells form in direct vicinity to surgical suture material. These cells stained positive for cathepsin K, which is a typical protease found in osteoclasts. By in vitro analysis, we were able to show that monocytes differentiated into osteoclasts when stimulated with surgical suture material. Resorption pits on ivory slices provided proof that the osteoclasts were functional. Release of IL-8 into cell supernatant was increased after stimulation with suture material and was further enhanced if minor amounts of bacterial lipoteichoic acid (LTA) were added. Neutrophils were also activated by surgical suture material and up-regulation of CD11b and CD66b could be seen.
Conclusion: We were able to demonstrate that surgical suture material induces a pro-inflammatory response of immune cells which leads to osteoclast differentiation, in particular in combination with bacterial infection. In conclusion, surgical suture material -aside from bacteria and implant wear particles- is a contributing factor in implant loosening.
Keywords: Osteoclast, osteolysis, surgical suture material, implant-associated infection, Interleukin-8