1. Consequences of particles formation Increase in total surface area Local tissue response and release of cytokines involved in bone resorption Biological response

2. B.F. Morrey, Biological, Material, and Mechanical Considerations of Joint Replacement, 1993 Local tissue response Biological response

3. Consequences of particles formation Increase in total surface area Local tissue response and release of cytokines involved in bone resorption Systemic effects Biological response

4. Hip prosthesis implanted 2-year post- op Systemic effect of metal particles– blood and urine I. Milošev, P. Campbell, V. Pišot, J.Orhop. Res., 23 (2005) 526-535 Biological response

5. Consequences of particles formation Increase in total surface area Local tissue response and release of cytokines involved in bone resorption Systemic effects Transport of particles to distant organs Potential for carcinogenesis and hypersensitivity Biological response

6. Metal sensitivity Skin test for metal sensitivity are not correlative and are unable to predict delayed metal hypersensitivity !

7. Willert HG et al., Osteologie (2000), World Tribology Forum in Artroplasty (2001) Delayed Type Hypersensitivity (DTH) related to the use of metal-on-metal prostheses: Diffuse and perivascularly oriented lymphocyte infiltration Macrophages (sometimes with drop-like inclusions) Plasma cells* Infiltrates of B-lymphocytes* Massive fibrin exudations* Clinical status: pain

8. Concluding remarks Benefits of total joint replacements are most important fot the patient. We should be aware, however, that loosened implant components are a source of various types of nanoparticles – metal, polyethylene, PMMA and ceramic. Knowledge on their morphology and composition contributes to the understanding of failure mechanism. Efforts are directed to the prolongation of life- time of implants by increasing their wear resistance. Joint collaboration studies between medical and research community are necessary.

9. Acknowledgments Orhopaedic surgeons at the Valdoltra Orthopaedic Hospital (V. Pišot, R. Trebše, S. Kovač) Vesna Levašič, MD, Arthroplasty register Prof. Andrej Coer, University of Primorska, pathology specialist Dr. Maja Remškar, Jožef Stefan Institute Thank you

10. Ceramic particles origin: femoral head acetabular inlay Wear debriswww.endoplus.com

11. www.ceramtec.comwww.wmt.com Novel bearing combinations Lower wear implies a lower number of wear debris particles and, consequently, a decreased incidence of aseptic loosening. However, other problems may arise.

12. Primary hip and knee total hip replacements at the Valdoltra Orthopaedic Hospital

13. Femoral head Femoral stem, Femoral stem Femoral head, Fracture plate femoral head acetabular inlay acetabular inlay Stainless steel Cobalt- base alloys Titanium- base alloys Ceramics + price availability Wear resistance Corrosion resistance Fatique resistance Corrosion resistance Elastic modulus Fatique resistance Specific density Biocompatibili ty Wear resistance Corrosion resistance Specific density Biocompatibili ty - Elastic modulus Biocompatibili ty Elastic modulus Biocompatibili ty Elastic modulus Biocompatibili ty Elastic modulus Fracture

14. Diffusely distributed lymphocytic infiltrates Perivascular lymphocytic infiltrates

15. Origin of wear debris and their transport in the body A – Cemented prostheses; B – Uncemented prostheses H.-G. Willert, et al., “Biological, Material and Mechanical Considerations of Joint Replacement”, 1993 Wear debris wear debris particles

16. Bone cement particles origin: femoral stem acetabular cup Wear debris Cortical bone Cancellous bone Bone cement Polyethylene Metal

17. Ceramic wear particles Wear debris

18. Procedure for isolation of metal and polyethylene particles from periprosthetic tissue using hydroxide digestion Digest minced tissue in 5M NaOH at 65 o C Ultrasonicate for 10 minutes Centrifugate at 6000 rpm for 1h Top layer contains polyethylene particles Bottom layer contains metal particles Hydrolyse at 80 o C for 1h Ultrasonicate for 5 minutes Add 3 ml of isopropanol Centrifugate at 6000 rpm for 1 h Wear debris

19. Hip prosthesis explanted 2-year post- op Systemic effect of metal particles– blood and urine I. Milošev, P. Campbell, V. Pišot, J.Orhop. Res., 23 (2005) 526-535 Biological response

20. Cr-O-particle Ti-particle

21. Ca-P-O-particle Different composition of particles arises from the formation of solid lubricating layer at the surface containing denatured proteins and metal oxides. I. Milošev, M. Remškar, J. Biomed. Mater. Res., in press

22. Different composition of particles arises from the formation of solid lubricating layer at the surface containing denatured proteins and metal oxides. a c b a c b