Clinical Orthopaedics and Related Research®

, Volume 471, Issue 8, pp 2532–2539

A Silver Ion-doped Calcium Phosphate-based Ceramic Nanopowder-coated Prosthesis Increased Infection Resistance

  • Nusret Kose
  • Ali Otuzbir
  • Ceren Pekşen
  • Abdurrahman Kiremitçi
  • Aydın Doğan
Symposium: Nanoscience in Musculoskeletal Medicine



Despite progress in surgical techniques, 1% to 2% of joint arthroplasties become complicated by infection. Coating implant surfaces with antimicrobial agents have been attempted to prevent initial bacterial adhesion to implants with varying success rates. We developed a silver ion-containing calcium phosphate-based ceramic nanopowder coating to provide antibacterial activity for orthopaedic implants.


We asked whether titanium prostheses coated with this nanopowder would show resistance to bacterial colonization as compared with uncoated prostheses.


We inserted titanium implants (uncoated [n = 9], hydroxyapatite-coated [n = 9], silver-coated [n = 9]) simulating knee prostheses into 27 rabbits’ knees. Before implantation, 5 × 102 colony-forming units of Staphylococcus aureus were inoculated into the femoral canal. Radiology, microbiology, and histology findings were quantified at Week 6 to define the infection, microbiologically by increased rate of implant colonization/positive cultures, histologically by leukocyte infiltration, necrosis, foreign-body granuloma, and devitalized bone, and radiographically by periosteal reaction, osteolysis, or sequestrum formation.


Swab samples taken from medullary canals and implants revealed a lower proportion of positive culture in silver-coated implants (one of nine) than in uncoated (eight of nine) or hydroxyapatite-coated (five of nine) implants. Silver-coated implants also had a lower rate of colonization. No cellular inflammation or foreign-body granuloma was observed around the silver-coated prostheses.


Silver ion-doped ceramic nanopowder coating of titanium implants led to an increase in resistance to bacterial colonization compared to uncoated implants.

Clinical Relevance

Silver-coated orthopaedic implants may be useful for resistance to local infection but will require in vivo confirmation.


  1. 1.
    Aktekin CN, Ozturk AM, Tabak AY, Altay M, Korkusuz F. A different perspective for radiological evaluation of experimental osteomyelitis. Skeletal Radiol. 2007;36:945–950.PubMedCrossRefGoogle Scholar
  2. 2.
    Alt V, Bitschnau A, Osterling J, Sewing A, Meyer C, Kraus R, Meissner SA, Wenisch S, Domann E, Schnettler R. The effects of combined gentamicin-hydroxyapatite coating for cementless joint prostheses on the reduction of infection rates in a rabbit infection prophylaxis model. Biomaterials. 2006;27:4627–4634.PubMedCrossRefGoogle Scholar
  3. 3.
    Bai X, More K, Rouleau CM, Rabiei A. Functionally graded hydroxyapatite coatings doped with antibacterial components. Acta Biomater. 2010;6:2264–2273.PubMedCrossRefGoogle Scholar
  4. 4.
    Bosetti M, Masse A, Tobin E, Cannas M. Silver coated materials for external fixation devices: in vitro biocompatibility and genotoxicity. Biomaterials. 2002;23:887–892.PubMedCrossRefGoogle Scholar
  5. 5.
    Chen W, Liu Y, Courtney HS, Bettenga M, Agrawal CM, Bumgardner JD, Ong JL. In vitro antibacterial and biological properties of magnetron co-sputtered silver-containing hydroxyapatite coating. Biomaterials. 2006;27:5512–5517.PubMedCrossRefGoogle Scholar
  6. 6.
    Chen W, Oh S, Ong AP, Oh N, Liu Y, Courtney HS, Appleford M, Ong JL. Antibacterial and osteogenic properties hydroxyapatite coatings produced using of silver-containing a sol gel process. J Biomed Mater Res A. 2007;82:899–906.PubMedGoogle Scholar
  7. 7.
    Chen Y, Zheng X, Xie Y, Ding C, Ruan H, Fan C. Anti-bacterial and cytotoxic properties of plasma sprayed silver-containing HA coatings. J Mater Sci Mater Med. 2008;19:3603–3609.PubMedCrossRefGoogle Scholar
  8. 8.
    Collinet-Adler S, Castro CA, Ledonio CG, Bechtold JE, Tsukayama DT. Acinetobacter baumannii is not associated with osteomyelitis in a rat model: a pilot study. Clin Orthop Relat Res. 2011;469:274–282.PubMedCrossRefGoogle Scholar
  9. 9.
    Darouiche RO. Anti-infective efficacy of silver-coated medical prostheses. Clin Infect Dis. 1999;29:1371–1377.PubMedCrossRefGoogle Scholar
  10. 10.
    Darouiche RO. Treatment of infections associated with surgical implants. N Engl J Med. 2004;350:1422–1429.PubMedCrossRefGoogle Scholar
  11. 11.
    Darouiche RO, Mansouri MD, Zakarevicz D, Alsharif A, Landon GC. In vivo efficacy of antimicrobial-coated devices. J Bone Joint Surg Am. 2007;89:792–797.PubMedCrossRefGoogle Scholar
  12. 12.
    Darouiche RO, Raad II, Bodey GP, Musher DM. Antibiotic susceptibility of staphylococcal isolates from patients with vascular catheter-related bacteremia: potential role of the combination of minocycline and rifampin. Int J Antimicrob Agents. 1995;6:31–36.PubMedCrossRefGoogle Scholar
  13. 13.
    Garvin KL, Hanssen AD. Current concepts review: infection after total hip arthroplasty. J Bone Joint Surg Am. 1995;77:1576–1588.PubMedGoogle Scholar
  14. 14.
    Gosheger G, Hardes J, Ahrens H, Streitburger A, Buerger H, Erren M, Gunsel A, Kemper FH, Winkelmann W, Von Eiff C. Silver-coated megaendoprostheses in a rabbit model—an analysis of the infection rate and toxicological side effects. Biomaterials. 2004;25:5547–5556.PubMedCrossRefGoogle Scholar
  15. 15.
    Gristina G, Costerton JW. Bacterial adherence and the glycocalyx and their role in musculoskeletal infection. Orthop Clin North Am. 1984;15:517–535.PubMedGoogle Scholar
  16. 16.
    Grunlan JC, Choi JK, Lin A. Antimicrobial behavior of polyelectrolyte multilayer films containing cetrimide and silver. Biomacromolecules. 2005;6:1149–1153.PubMedCrossRefGoogle Scholar
  17. 17.
    Hardes J, Ahrens H, Gebert C, Streitbuerger A, Buerger H, Erren M, Gunsel A, Wedemeyer C, Saxler G, Winkelmann W, Gosheger G. Lack of toxicological side-effects in silver coated megaprostheses in humans. Biomaterials. 2007;28:2869–2875.PubMedCrossRefGoogle Scholar
  18. 18.
    Hendriks JG, van Horn JR, van der Mei HC, Busscher HJ. Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection. Biomaterials. 2004;25:545–556.PubMedCrossRefGoogle Scholar
  19. 19.
    Isiklar ZU, Darouiche RO, Landon GC, Beck T. Efficacy of antibiotics alone for orthopaedic device related infections. Clin Orthop Relat Res. 1996;332:184–189.PubMedCrossRefGoogle Scholar
  20. 20.
    Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH. Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol. 2008;74:2171–2178.PubMedCrossRefGoogle Scholar
  21. 21.
    Leeuwenburgh S, Wolke J, Schoonman J, Jansen JA. Influence of deposition parameters on chemical properties of calcium phosphate coatings prepared by using electrostatic spray deposition. J Biomed Mater Res A. 2005;74:275–284.PubMedGoogle Scholar
  22. 22.
    Nasser S. Prevention and treatment of sepsis in total hip replacement surgery. Orthop Clin North Am. 1992;23:265–277.PubMedGoogle Scholar
  23. 23.
    Noda I, Miyaji F, Ando Y, Miyamoto H, Shimazaki T, Yonekura Y, Miyazaki M, Mawatari M, Hotokebuchi T. Development of novel thermal sprayed antibacterial coating and evaluation of release properties of silver ions. J Biomed Mater Res B Appl Biomater. 2009;89:456–465.PubMedGoogle Scholar
  24. 24.
    Peterson JJ. Postoperative infection. Radiol Clin North Am. 2006;44:439–450.PubMedCrossRefGoogle Scholar
  25. 25.
    Petty W, Spanier S, Shuster JJ, Silverthorne C. The influence of skeletal implants on incidence of infection: experiment in a canine model. J Bone Joint Surg Am. 1985;67;1236–1244.PubMedGoogle Scholar
  26. 26.
    Sculco TP. The economic impact of infected joint arthroplasty. Orthopedics. 1995;18:871–873.PubMedGoogle Scholar
  27. 27.
    Song WH, Ryu HS, Hong SH. Antibacterial properties of Ag (or Pt)-containing calcium phosphate coating formed by micro-arc oxidation. J Biomed Mater Res A. 2009;88:246–254.PubMedGoogle Scholar
  28. 28.
    Taniguchi I, Schoonman J. Electrostatic spray deposition of perovskite-type oxide thin films with porous microstructure. J Mater Synth Process. 2002;10:267–275.CrossRefGoogle Scholar
  29. 29.
    Thian ES, Li X, Huang J, Edirisinghe MJ, Bonfield W, Best SM. Electrospray deposition of nanohydroxyapatite coatings: a strategy to mimic bone apatite mineral. Thin Solid Films. 2011;519:2328–2331.CrossRefGoogle Scholar
  30. 30.
    Vik H, Andersen KJ, Julshamn K, Todnem K. Neuropathy caused by silver absorption from arthroplasty cement. Lancet. 1985;1:872.PubMedCrossRefGoogle Scholar
  31. 31.
    Vogely HC, Oosterbos CJ, Puts EW, Nijhof MW, Nikkels PG, Fleer A, Tonino AJ, Dhert WJ, Verbout AJ. Effects of hydroxyapatite coating on Ti-6A1-4V implant-site infection in a rabbit tibial model. J Orthop Res. 2000;18:485–493.PubMedCrossRefGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons® 2013

Authors and Affiliations

  • Nusret Kose
    • 1
  • Ali Otuzbir
    • 1
  • Ceren Pekşen
    • 2
  • Abdurrahman Kiremitçi
    • 3
  • Aydın Doğan
    • 2
  1. 1.Department of Orthopaedics and Traumatology, Medical FacultyOsmangazi UniversityEskisehirTurkey
  2. 2.Department of Materials Science and EngineeringAnadolu UniversityEskisehirTurkey
  3. 3.Department of Microbiology, Medical FacultyOsmangazi UniversityEskisehirTurkey

Personalised recommendations