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Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty

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Abstract

The aim of this study was the investigation of a copper-filled TiO2 coating, that in vitro showed good antibacterial properties combined with good tissue tolerance in an animal model. To better understand the antibacterial mechanism of the bioactive coating the release of copper (Cu) ions over time was monitored to be able to detect possible threats as well as possible fields of application. 30 New Zealand White rabbits were divided into two groups with 15 animals per group. In group 1 (control group) Ti6Al4 V bolts were implanted into the distal femur, in group 2 the Ti6Al4 V bolts were coated with four TiO2-coatings with integrated Cu2+-ions (4 × Cu–TiO2). Blood tests were performed weekly until the animals were sacrificed 4 weeks postoperative. The maximum peak of Cu and ceruloplasmin concentration could be seen in both groups one week postoperative, whereas the Cu values in group II were significantly higher. The Cu concentration in both groups approximated the initial basic values 4 weeks postoperative. The 4 × Cu–TiO2 coating tested in our rabbit model for total knee arthroplasty is an active coating that releases potentially antibacterial Cu2+ for 4 weeks with a peak 1 week postoperative. The bioactive coating could be a promising approach for a use in the field of implant related infection, orthopaedic revision and tumor surgery in the future.

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References

  1. Blom AW, Taylor AH, Pattison G, Whitehouse S, Bannister GC. Infection after total hip arthroplasty. The Avon experience. J Bone Joint Surg Br. 2003;85(7):956–9.

    Article  Google Scholar 

  2. Phillips JE, Crane TP, Noy M, Elliott TS, Grimer RJ. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint Surg Br. 2006;88(7):943–8. doi:10.1302/0301-620X.88B7.17150.

    Article  Google Scholar 

  3. Kurtz SM, Lau E, Schmier J, Ong KL, Zhao K, Parvizi J. Infection burden for hip and knee arthroplasty in the United States. J Arthroplasty. 2008;23(7):984–91. doi:10.1016/j.arth.2007.10.017.

    Article  Google Scholar 

  4. Beswick AD, Elvers KT, Smith AJ, Gooberman-Hill R, Lovering A, Blom AW. What is the evidence base to guide surgical treatment of infected hip prostheses? systematic review of longitudinal studies in unselected patients. BMC Med. 2012;10:18. doi:10.1186/1741-7015-10-18.

    Article  Google Scholar 

  5. Zhao L, Chu PK, Zhang Y, Wu Z. Antibacterial coatings on titanium implants. J Biomed Mater Res B. 2009;91(1):470–80. doi:10.1002/jbm.b.31463.

    Article  Google Scholar 

  6. Heidenau F, Mittelmeier W, Detsch R, Haenle M, Stenzel F, Ziegler G, et al. A novel antibacterial titania coating: metal ion toxicity and in vitro surface colonization. J Mater Sci Mater Med. 2005;16(10):883–8. doi:10.1007/s10856-005-4422-3.

    Article  Google Scholar 

  7. Haenle M, Fritsche A, Zietz C, Bader R, Heidenau F, Mittelmeier W, et al. An extended spectrum bactericidal titanium dioxide (TiO2) coating for metallic implants: in vitro effectiveness against MRSA and mechanical properties. J Mater Sci Mater Med. 2011;22(2):381–7. doi:10.1007/s10856-010-4204-4.

    Article  Google Scholar 

  8. Craig MR, Poelstra KA, Sherrell JC, Kwon MS, Belzile EL, Brown TE. A novel total knee arthroplasty infection model in rabbits. J Orthop Res. 2005;23(5):1100–4. doi:10.1016/j.orthres.2005.03.007.

    Article  Google Scholar 

  9. R-Core-Team. R: a language and environment for statistical computing. Vienna: R-Core-Team; 2012.

    Google Scholar 

  10. Sato M, Gitlin JD. Mechanisms of copper incorporation during the biosynthesis of human ceruloplasmin. J Biol Chem. 1991;266(8):5128–34.

    Google Scholar 

  11. Gitlin JD, Schroeder JJ, Lee-Ambrose LM, Cousins RJ. Mechanisms of caeruloplasmin biosynthesis in normal and copper-deficient rats. Biochem J. 1992;282(Pt 3):835–9.

    Google Scholar 

  12. Bielli P, Calabrese L. Structure to function relationships in ceruloplasmin: a ‘moonlighting’ protein. Cell Mol Life Sci. 2002;59(9):1413–27.

    Article  Google Scholar 

  13. Senra Varela A, Lopez Saez JJ, Quintela Senra D. Serum ceruloplasmin as a diagnostic marker of cancer. Cancer Lett. 1997;121(2):139–45.

    Article  Google Scholar 

  14. Stassar MJ, Devitt G, Brosius M, Rinnab L, Prang J, Schradin T, et al. Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001;85(9):1372–82. doi:10.1054/bjoc2001.2074.

    Article  Google Scholar 

  15. Wang KK, Liu N, Radulovich N, Wigle DA, Johnston MR, Shepherd FA, et al. Novel candidate tumor marker genes for lung adenocarcinoma. Oncogene. 2002;21(49):7598–604. doi:10.1038/sj.onc.1205953.

    Article  Google Scholar 

  16. Harris ZL, Gitlin JD. Genetic and molecular basis for copper toxicity. Am J Clin Nutr. 1996;63(5):836S–41S.

    Google Scholar 

  17. Calabrese L, Carbonaro M, Musci G. Chicken ceruloplasmin. Evidence in support of a trinuclear cluster involving type 2 and 3 copper centers. J Biol Chem. 1988;263(14):6480–3.

    Google Scholar 

  18. Danzeisen R, Araya M, Harrison B, Keen C, Solioz M, Thiele D, et al. How reliable and robust are current biomarkers for copper status? Br J Nutr. 2007;98(4):676–83. doi:10.1017/S0007114507798951.

    Article  Google Scholar 

  19. Pizarro F, Olivares M, Uauy R, Contreras P, Rebelo A, Gidi V. Acute gastrointestinal effects of graded levels of copper in drinking water. Environ Health Perspect. 1999;107(2):117–21.

    Article  Google Scholar 

  20. Araya M, Olivares M, Pizarro F, Gonzalez M, Speisky H, Uauy R. Gastrointestinal symptoms and blood indicators of copper load in apparently healthy adults undergoing controlled copper exposure. Am J Clin Nutr. 2003;77(3):646–50.

    Google Scholar 

  21. Arredondo M, Gonzalez M, Olivares M, Pizarro F, Araya M. Ceruloplasmin, an indicator of copper status. Biol Trace Elem Res. 2008;123(1–3):261–9. doi:10.1007/s12011-008-8110-2.

    Article  Google Scholar 

  22. Antoniou J, Zukor DJ, Mwale F, Minarik W, Petit A, Huk OL. Metal ion levels in the blood of patients after hip resurfacing: a comparison between twenty-eight and thirty-six-millimeter-head metal-on-metal prostheses. J Bone Joint Surg Am. 2008;90(Suppl 3):142–8. doi:10.2106/JBJS.H.00442.

    Article  Google Scholar 

  23. Clarke MT, Lee PT, Arora A, Villar RN. Levels of metal ions after small- and large-diameter metal-on-metal hip arthroplasty. J Bone Joint Surg Br. 2003;85(6):913–7.

    Google Scholar 

  24. Vendittoli PA, Mottard S, Roy AG, Dupont C, Lavigne M. Chromium and cobalt ion release following the Durom high carbon content, forged metal-on-metal surface replacement of the hip. J Bone Joint Surg Br. 2007;89(4):441–8. doi:10.1302/0301-620X.89B4.18054.

    Article  Google Scholar 

  25. Skipor AK, Campbell PA, Patterson LM, Anstutz HC, Schmalzried TP, Jacobs JJ. Serum and urine metal levels in patients with metal-on-metal surface arthroplasty. J Mater Sci Mater Med. 2002;13(12):1227–34.

    Article  Google Scholar 

  26. Back DL, Young DA, Shimmin AJ. How do serum cobalt and chromium levels change after metal-on-metal hip resurfacing? Clin Orthop Relat Res. 2005;438:177–81.

    Article  Google Scholar 

  27. Wagner P, Olsson H, Ranstam J, Robertsson O, Zheng MH, Lidgren L. Metal-on-metal joint bearings and hematopoetic malignancy. Acta Orthop. 2012;83(6):553–8. doi:10.3109/17453674.2012.747055.

    Article  Google Scholar 

  28. Little MP. Cancer and non-cancer effects in Japanese atomic bomb survivors. J Radiol Prot. 2009;29(2A):A43–59. doi:10.1088/0952-4746/29/2A/S04.

    Article  Google Scholar 

  29. Araya M, Olivares M, Pizarro F, Gonzalez M, Speisky H, Uauy R. Copper exposure and potential biomarkers of copper metabolism. Biometals. 2003;16(1):199–204.

    Article  Google Scholar 

  30. Turnlund JR, Keyes WR, Peiffer GL, Scott KC. Copper absorption, excretion, and retention by young men consuming low dietary copper determined by using the stable isotope 65Cu. Am J Clin Nutr. 1998;67(6):1219–25.

    Google Scholar 

  31. Turnlund JR, Keyes WR, Anderson HL, Acord LL. Copper absorption and retention in young men at three levels of dietary copper by use of the stable isotope 65Cu. Am J Clin Nutr. 1989;49(5):870–8.

    Google Scholar 

  32. Harvey LJ, Majsak-Newman G, Dainty JR, Lewis DJ, Langford NJ, Crews HM, et al. Adaptive responses in men fed low- and high-copper diets. Br J Nutr. 2003;90(1):161–8.

    Article  Google Scholar 

  33. Araya M, Kelleher SL, Arredondo MA, Sierralta W, Vial MT, Uauy R, et al. Effects of chronic copper exposure during early life in rhesus monkeys. Am J Clin Nutr. 2005;81(5):1065–71.

    Google Scholar 

  34. Keen CL, Graham TW. Trace elements. Clinical biochemistry of domestic animals. 4th ed. New York: Academic Press Inc; 1989.

    Google Scholar 

  35. Singh KK, Gupta MK, Ram M, Singh V, Roy BK. Effect of chronic fenvalerate intoxication on tissue concentration of copper in goats and further exploration of its mechanism. Biol Trace Elem Res. 2010;138(1–3):163–72. doi:10.1007/s12011-010-8629-x.

    Article  Google Scholar 

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Acknowledgments

We gratefully acknowledge the “medrasys GmbH, medical technologies”, Pressig, Germany for providing the funding to realize the Project.

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Correspondence to Andreas Mauerer.

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Mauerer, A., Lange, B., Welsch, G.H. et al. Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty. J Mater Sci: Mater Med 25, 813–821 (2014). https://doi.org/10.1007/s10856-013-5116-x

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  • DOI: https://doi.org/10.1007/s10856-013-5116-x

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