Advertisement

Anti-Infection Technologies for Orthopedic Implants: Materials and Considerations for Commercial Development

  • David Armbruster
Chapter

Abstract

Orthopedic implant-related infection is a difficult clinical challenge, and a common cause of implant failure. Often due to bacterial biofilms formed on the implant surface, this unmet clinical need presents an opportunity for the development of new material technologies to make orthopedic implant surfaces less hospitable to bacterial colonization. Anti-infection material technologies are divided generally into three categories: passive surface modifications, active surface modifications, and perioperative local antibiotic carriers or coatings. Significant research has been published on technologies in each of these categories, and each approach offers potential advantages. Development of any anti-infection technology in orthopedics is made more difficult by the lack of good preclinical models of implant-related infection, a complex regulatory environment, a fragmented market, and indication-specific requirements for clinical data. Successful commercialization will depend on the identification of technical solutions to these nontechnical challenges.

Keywords

Infection Biofilm Orthopedic Coating Staphylococcus Bacteria Surface modification Antibiotic Antimicrobial Silver PMMA Regulatory FDA 

References

  1. 1.
    Bozic KJ, Kurtz SM, Lau E, et al. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2010;468(1):45–51.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Southwood RT, Rice JL, McDonald PJ, et al. Infection in experimental hip arthroplasties. J Bone Joint Surg Br. 1985;67(2):229–31.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Rezapoor M, Parvizi J. Prevention of periprosthetic joint infection. J Arthroplasty. 2015;30(6):902–7.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Voigt J, Mosier M, Darouiche R. Systematic review and meta-analysis of randomized controlled trials of antibiotics and antiseptics for preventing infection in people receiving primary total hip and knee prostheses. Antimicrob Agents Chemother. 2015;59(11):6696–707.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Stambough JB, Nam D, Warren DK, et al. Decreased hospital costs and surgical site infection incidence with a universal decolonization protocol in primary total joint arthroplasty. J Arthroplasty. 2017;32(3):728–34.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Gristina AG. Biomaterial-centered infection: microbial adhesion versus tissue integration. Science. 1987;237(4822):1588–95.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Busscher HJ, van der Mei HC, Subbiahdoss G, et al. Biomaterial-associated infection: locating the finish line in the race for the surface. Sci Transl Med. 2012;4(153):153rv10.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Zaborowska M, Tillander J, Brånemark R, et al. Biofilm formation and antimicrobial susceptibility of staphylococci and enterococci from osteomyelitis associated with percutaneous orthopaedic implants. J Biomed Mater Res B Appl Biomater. 2016. https://doi.org/10.1002/jbm.b.33803.
  9. 9.
    Arciola CR, Campoccia D, Speziale P, et al. Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. Biomaterials. 2012;33(26):5967–82.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Costerton JW, Montanaro L, Arciola CR. Biofilm in implant infections: its production and regulation. Int J Artif Organs. 2005;28(11):1062–8.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Archer NK, Mazaitis MJ, Costerton JW, et al. Staphylococcus aureus biofilms: properties, regulation, and roles in human disease. Virulence. 2011;2(5):445–59.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Stoodley P, Ehrlich GD, Sedghizadeh PP, et al. Orthopaedic biofilm infections. Curr Orthop Pract. 2011;22(6):558–63.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Torbert JT, Joshi M, Moraff A, et al. Current bacterial speciation and antibiotic resistance in deep infections after operative fixation of fractures. J Orthop Trauma. 2015;29(1):7–17.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Drago L, De Vecchi E, Bortolin M, et al. Epidemiology and antibiotic resistance of late prosthetic knee and hip infections. J Arthroplasty. 2017 Mar;32(8):2496–500.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Palmer MP, Altman DT, Altman GT, et al. Can we trust intraoperative culture results in nonunions? J Orthop Trauma. 2014;28(7):384–90.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Palmer M, Costerton JW, Sewecke J, et al. Molecular techniques to detect biofilm bacteria in long bone nonunion: a case report. Clin Orthop Relat Res. 2011;469(11):3037–42. https://doi.org/10.1007/s11999-011-1843-9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Fraunholz M, Sinha B. Intracellular staphylococcus aureus: live-in and let die. Front Cell Infect Microbiol. 2012;2:43.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Broekhuizen CA, de Boer L, Schipper K, et al. Staphylococcus epidermidis is cleared from biomaterial implants but persists in peri-implant tissue in mice despite rifampicin/vancomycin treatment. J Biomed Mater Res A. 2008;85(2):498–505.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Sendi P, Proctor RA. Staphylococcus aureus as an intracellular pathogen: the role of small colony variants. Trends Microbiol. 2009;17(2):54–8. https://doi.org/10.1016/j.tim.2008.11.004.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    de Mesy Bentley KL, Trombetta R, Nishitani K, et al. Evidence of staphylococcus aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis. J Bone Miner Res. 2017;32(5):985–90.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Berríos-Torres SI, Umscheid CA, Bratzler DW, Healthcare Infection Control Practices Advisory Committee, et al. Centers for disease control and prevention guideline for the prevention of surgical site infection. JAMA Surg. 2017;152(8):784–91.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Hake ME, Young H, Hak DJ, et al. Local antibiotic therapy strategies in orthopaedic trauma: practical tips and tricks and review of the literature. Injury. 2015;46(8):1447–56.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Singh K, Bauer JM, LaChaud GY, et al. Surgical site infection in high-energy peri-articular tibia fractures with intra-wound vancomycin powder: a retrospective pilot study. J Orthop Traumatol. 2015;16(4):287–91.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Romanò CL, Scarponi S, Gallazzi E, et al. Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama. J Orthop Surg Res. 2015;10:157.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Willis-Owen CA, Konyves A, Martin DK. Factors affecting the incidence of infection in hip and knee replacement: an analysis of 5277 cases. J Bone Joint Surg Br. 2010;92(8):1128–33. https://doi.org/10.1302/0301-620X.92B8.24333.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Garrett TR, Bhakoo M, Zhang Z. Bacterial adhesion and biofilms on surfaces. Progress in Natural Science. 2008;18(9):1049–56.CrossRefGoogle Scholar
  27. 27.
    Metsemakers WJ, Schmid T, Zeiter S, et al. Titanium and steel fracture fixation plates with different surface topographies: influence on infection rate in a rabbit fracture model. Injury. 2016;47(3):633–9.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Bagherifard S, Hickey DJ, de Luca AC, et al. The influence of nanostructured features on bacterial adhesion and bone cell functions on severely shot peened 316L stainless steel. Biomaterials. 2015;73:185–97.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Kummer KM, Taylor EN, Durmas NG, et al. Effects of different sterilization techniques and varying anodized TiO2 nanotube dimensions on bacteria growth. J Biomed Mater Res B Appl Biomater. 2013;101(5):677–88. https://doi.org/10.1002/jbm.b.32870. Epub 2013 Jan 29.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bhardwaj G, Webster TJ. Reduced bacterial growth and increased osteoblast proliferation on titanium with a nanophase TiO2 surface treatment. Int J Nanomedicine. 2017;12:363–9.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Visai L, De Nardo L, Punta C, et al. Titanium oxide antibacterial surfaces in biomedical devices. Int J Artif Organs. 2011;34(9):929–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Fujishima A, Zhangb X, Tryk DA. TiO2 photocatalysis and related surface phenomena. Surf Sci Rep. 2008;63:515–82.CrossRefGoogle Scholar
  33. 33.
    Foster HA, Ditta IB, Varghese S, et al. Photocatalytic disinfection using titanium dioxide: spectrum and mechanism of antimicrobial activity. Appl Microbiol Biotechnol. 2011;90(6):1847–68.PubMedCrossRefGoogle Scholar
  34. 34.
    Roach MD, Williamson RS, Blakely IP, et al. Tuning anatase and rutile phase ratios and nanoscale surface features by anodization processing onto titanium substrate surfaces. Mater Sci Eng C Mater Biol Appl. 2016;58:213–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Lilja M, Welch K, Astrand M, et al. Effect of deposition parameters on the photocatalytic activity and bioactivity of TiO2 thin films deposited by vacuum arc on Ti-6Al-4V substrates. J Biomed Mater Res B Appl Biomater. 2012;100(4):1078–85.PubMedCrossRefGoogle Scholar
  36. 36.
    Dunlop PS, Sheeran CP, Byrne JA, et al. Inactivation of clinically relevant pathogens by photocatalytic coatings. J Photochem Photobiol A. 2010;216(2):303–10.CrossRefGoogle Scholar
  37. 37.
    Yue C, Kuijer R, Kaper HJ, et al. Simultaneous interaction of bacteria and tissue cells with photocatalytically activated, anodized titanium surfaces. Biomaterials. 2014;35(9):2580–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Jose B, Antoci V Jr, Zeiger AR, et al. Vancomycin covalently bonded to titanium beads kills Staphylococcus aureus. Chem Biol. 2005;12(9):1041-1048.Google Scholar
  39. 39.
    Antoci V Jr, Adams CS, Parvizi J, et al. The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection. Biomaterials. 2008;29(35):4684–90.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Shapiro IM, Hickok NJ, Parvizi J, et al. Molecular engineering of an orthopaedic implant: from bench to bedside. Eur Cell Mater. 2012;23:362–70.PubMedCrossRefGoogle Scholar
  41. 41.
    Antoci V Jr, Adams CS, Hickok NJ, et al. Vancomycin bound to Ti rods reduces periprosthetic infection: preliminary study. Clin Orthop Relat Res. 2007;461:88–95.PubMedGoogle Scholar
  42. 42.
    Stewart S, Barr S, Engiles J, et al. Vancomycin-modified implant surface inhibits biofilm formation and supports bone-healing in an infected osteotomy model in sheep: a proof-of-concept study. J Bone Joint Surg Am. 2012;94(15):1406–15.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Nie B, Ao H, Long T, et al. Immobilizing bacitracin on titanium for prophylaxis of infections and for improving osteoinductivity: An in vivo study. Colloids Surf B Biointerfaces. 2017;150:183–91.PubMedCrossRefGoogle Scholar
  44. 44.
    Chen R, Willcox MD, Ho KK, et al. Antimicrobial peptide melimine coating for titanium and its in vivo antibacterial activity in rodent subcutaneous infection models. Biomaterials. 2016;85:142–51.PubMedCrossRefGoogle Scholar
  45. 45.
    Godoy-Gallardo M, Mas-Moruno C, Fernández-Calderón MC, et al. Covalent immobilization of hLf1-11 peptide on a titanium surface reduces bacterial adhesion and biofilm formation. Acta Biomater. 2014;10(8):3522–34.PubMedCrossRefGoogle Scholar
  46. 46.
    Schaer TP, Stewart S, Hsu BB, et al. Hydrophobic polycationic coatings that inhibit biofilms and support bone healing during infection. Biomaterials. 2012;33(5):1245–54. https://doi.org/10.1016/j.biomaterials.2011.10.038.CrossRefPubMedGoogle Scholar
  47. 47.
    Levin PD. The effectiveness of various antibiotics in methyl methacrylate. J Bone Joint Surg Br. 1975;57(2):234–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Buchholz HW, Elson RA, Engelbrecht E, et al. Management of deep infection of total hip replacement. J Bone Joint Surg Br. 1981;63-B(3):342–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Cui Q, Mihalko WM, Shields JS, et al. Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty. J Bone Joint Surg Am. 2007;89(4):871–82.PubMedGoogle Scholar
  50. 50.
    Bertazzoni Minelli E, Benini A, et al. Antimicrobial activity of gentamicin and vancomycin combination in joint fluids after antibiotic-loaded cement spacer implantation in two-stage revision surgery. J Chemother. 2015;27(1):17–24. https://doi.org/10.1179/1973947813Y.0000000157.CrossRefPubMedGoogle Scholar
  51. 51.
    Conway J, Mansour J, Kotze K, et al. Antibiotic cement-coated rods: an effective treatment for infected long bones and prosthetic joint nonunions. Bone Joint J. 2014;96-B(10):1349–54.PubMedCrossRefGoogle Scholar
  52. 52.
    Thonse R, Conway J. Antibiotic cement-coated interlocking nail for the treatment of infected nonunions and segmental bone defects. J Orthop Trauma. 2007;21(4):258–68.PubMedCrossRefGoogle Scholar
  53. 53.
    Ohtsuka H, Yokoyama K, Higashi K, et al. Use of antibiotic-impregnated bone cement nail to treat septic nonunion after open tibial fracture. J Trauma. 2002;52(2):364–6.PubMedGoogle Scholar
  54. 54.
    Eckman JB Jr, Henry SL, Mangino PD, et al. Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop Relat Res. 1988;237:213–5.Google Scholar
  55. 55.
    Lewis G. Properties of antibiotic-loaded acrylic bone cements for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater. 2009;89(2):558–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Meyer J, Piller G, Spiegel CA, et al. Vacuum-mixing significantly changes antibiotic elution characteristics of commercially available antibiotic-impregnated bone cements. J Bone Joint Surg Am. 2011;93(22):2049–56.PubMedCrossRefGoogle Scholar
  57. 57.
    Chang Y, Tai CL, Hsieh PH, et al. Gentamicin in bone cement: a potentially more effective prophylactic measure of infectionin joint arthroplasty. Bone Joint Res. 2013;2(10):220–6.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Neut D, van de Belt H, Stokroos I, et al. Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery. J Antimicrob Chemother. 2001;47(6):885–91.PubMedCrossRefGoogle Scholar
  59. 59.
    Anagnostakos K, Hitzler P, Pape D, et al. Persistence of bacterial growth on antibiotic-loaded beads: is it actually a problem? Acta Orthop. 2008;79(2):302–7. https://doi.org/10.1080/17453670710015120.CrossRefPubMedGoogle Scholar
  60. 60.
    Mäkinen TJ, Veiranto M, Knuuti J, et al. Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus. Bone. 2005;36(2):292–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Price JS, Tencer AF, Arm DM, et al. Controlled release of antibiotics from coated orthopedic implants. J Biomed Mater Res. 1996;30(3):281–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Gollwitzer H, Ibrahim K, Meyer H, et al. Antibacterial poly(D,L-lactic acid) coating of medical implants using a biodegradable drug delivery technology. J Antimicrob Chemother. 2003;51(3):585–91.PubMedCrossRefGoogle Scholar
  63. 63.
    Kälicke T, Schierholz J, Schlegel U, et al. Effect on infection resistance of a local antiseptic and antibiotic coating on osteosynthesis implants: an in vitro and in vivo study. J Orthop Res. 2006;24(8):1622–40.PubMedCrossRefGoogle Scholar
  64. 64.
    Lucke M, Schmidmaier G, Sadoni S, et al. Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone. 2003;32(5):521–31.PubMedCrossRefGoogle Scholar
  65. 65.
    Nast S, Fassbender M, Bormann N, et al. In vivo quantification of gentamicin released from an implant coating. J Biomater Appl. 2016;31(1):45–54.PubMedCrossRefGoogle Scholar
  66. 66.
    Vester H, Wildemann B, Schmidmaier G, et al. Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis. Injury. 2010;41(10):1053–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Fuchs T, Stange R, Schmidmaier G, et al. The use of gentamicin-coated nails in the tibia: preliminary results of a prospective study. Arch Orthop Trauma Surg. 2011;131(10):1419–25.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Metsemakers WJ, Reul M, Nijs S. The use of gentamicin-coated nails in complex open tibia fracture and revision cases: a retrospective analysis of a single centre case series and review of the literature. Injury. 2015;46(12):2433–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Neut D, Dijkstra RJ, Thompson JI, et al. A biodegradable gentamicin-hydroxyapatite-coating for infection prophylaxis in cementless hip prostheses. Eur Cell Mater. 2015;29:42–55.PubMedCrossRefGoogle Scholar
  70. 70.
    Metsemakers WJ, Emanuel N, Cohen O, et al. A doxycycline-loaded polymer-lipid encapsulation matrix coating for the prevention of implant-related osteomyelitis due to doxycycline-resistant methicillin-resistant Staphylococcus aureus. J Control Release. 2015;209:47–56.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Radin S, Ducheyne P, Kamplain T, et al. Silica sol-gel for the controlled release of antibiotics. I. Synthesis, characterization, and in vitro release. J Biomed Mater Res. 2001;57(2):313–20.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Qu H, Knabe C, Radin S, et al. Percutaneous external fixator pins with bactericidal micron-thin sol-gel films for the prevention of pin tract infection. Biomaterials. 2015;62:95–105.PubMedCrossRefGoogle Scholar
  73. 73.
    FDA. Draft guidance for industry and FDA staff: premarket notification [510(k)] submissions for medical devices that include antimicrobial agents 2007. https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm071396.pdf. Accessed 29 May 2017.
  74. 74.
    FDA. Guidance for industry and FDA staff: current good manufacturing practice requirements for combination products. 2015. https://www.fda.gov/downloads/regulatoryinformation/guidances/ucm429304.pdf. Accessed 29 May 2017.
  75. 75.
    Cai X, Han K, Cong X, et al. The use of calcium sulfate impregnated with vancomycin in the treatment of open fractures of long bones: a preliminary study. Orthopedics. 2010;33(3). https://doi.org/10.3928/01477447-20100129-17.
  76. 76.
    Emanuel N, Rosenfeld Y, Cohen O, et al. A lipid-and-polymer-based novel local drug delivery system-BonyPid™: from physicochemical aspects to therapy of bacterially infected bones. J Control Release. 2012;160(2):353–61. https://doi.org/10.1016/j.jconrel.2012.03.027.CrossRefPubMedGoogle Scholar
  77. 77.
    Alexander JW. History of the medical use of silver. Surg Infect (Larchmt). 2009;10(3):289–92.PubMedCrossRefGoogle Scholar
  78. 78.
    Lai NM, Chaiyakunapruk N, Lai NA, et al. Catheter impregnation, coating or bonding for reducing central venous catheter-related infections in adults. Cochrane Database of Syst Rev. 2013; (6): CD007878.Google Scholar
  79. 79.
    Lam TB, Omar MI, Fisher E, et al. Types of indwelling urethral catheters for short-term catheterisation in hospitalised adults. Cochrane Database Syst Rev. 2014; (9):CD004013.Google Scholar
  80. 80.
    Karchmer TB, Giannetta ET, Muto CA, et al. A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med. 2000;160(21):3294–8.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Feng QL, Wu J, Chen GQ, et al. A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J Biomed Mater Res. 2000;52(4):662–8.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Lansdown AB. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Mulley G, Jenkins AT, Waterfield NR. Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds. PLoS One. 2014;9(4):e94409.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Lansdown AB. Silver in healthcare: its antimicrobial efficacy and safety in use. Cambridge: RSC Publishing; 2010. https://doi.org/10.1039/9781849731799.CrossRefGoogle Scholar
  85. 85.
    Massè A, Bruno A, Bosetti M, et al. Prevention of pin track infection in external fixation with silver coated pins: clinical and microbiological results. J Biomed Mater Res. 2000;53(5):600–4.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Wassall MA, Santin M, Isalberti C, et al. Adhesion of bacteria to stainless steel and silver-coated orthopedic external fixation pins. J Biomed Mater Res. 1997;36(3):325–30.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Collinge CA, Goll G, Seligson D, et al. Pin tract infections: silver vs uncoated pins. Orthopedics. 1994;17(5):445–8.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Coester LM, Nepola JV, Allen J, et al. The effects of silver coated external fixation pins. Iowa Orthop J. 2006;26:48–53.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Schmidt-Braekling T, Streitbuerger A, Gosheger G, et al. Silver-coated megaprostheses: review of the literature. Eur J Orthop Surg Traumatol. 2017;27(4):483–9.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Donati F, Di Giacomo G, D'Adamio S, et al. Silver-coated hip megaprosthesis in oncological limb savage surgery. Biomed Res Int. 2016;2016:9079041.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Piccioli A, Donati F, Giacomo GD, et al. Infective complications in tumour endoprostheses implanted after pathological fracture of the limbs. Injury. 2016;47(Suppl 4):S22–8.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Hussmann B, Johann I, Kauther MD, et al. Measurement of the silver ion concentration in wound fluids after implantation of silver-coated megaprostheses: correlation with the clinical outcome. Biomed Res Int. 2013;2013:763096.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Hardes J, von Eiff C, Streitbuerger A, et al. Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma. J Surg Oncol. 2010;101(5):389–95.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Glehr M, Leithner A, Friesenbichler J, et al. Argyria following the use of silver-coated megaprostheses: no association between the development of local argyria and elevated silver levels. Bone Joint J. 2013;95-B(7):988–92.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Hardes J, Ahrens H, Gebert C, et al. Lack of toxicological side-effects in silver-coated megaprostheses in humans. Biomaterials. 2007;28(18):2869–75.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Wafa H, Grimer RJ, Reddy K, et al. Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients: case-control study. Bone Joint J. 2015;97-B(2):252–7.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Scoccianti G, Frenos F, Beltrami G, et al. Levels of silver ions in body fluids and clinical results in silver-coated megaprostheses after tumour, trauma or failed arthroplasty. Injury. 2016;47(Suppl 4):S11–6.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Hauschild G, Hardes J, Gosheger G, et al. Evaluation of osseous integration of PVD-silver-coated hip prostheses in a canine model. Biomed Res Int. 2015;2015:292406.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Khalilpour P, Lampe K, Wagener M, et al. Ag/SiO(x)C(y) plasma polymer coating for antimicrobial protection of fracture fixation devices. J Biomed Mater Res B Appl Biomater. 2010;94(1):196–202.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Zielinska E, Tukaj C, Radomski MW, et al. Molecular mechanism of silver nanoparticles-induced human osteoblast cell death: protective effect of inducible nitric oxide synthase inhibitor. PLoS One. 2016;11(10):e0164137.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Rosário F, Hoet P, Santos C, et al. Death and cell cycle progression are differently conditioned by the AgNP size in osteoblast-like cells. Toxicology. 2016;368-369:103–15.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Esfandiari N, Simchi A, Bagheri R. Size tuning of Ag-decorated TiO2 nanotube arrays for improved bactericidal capacity of orthopedic implants. J Biomed Mater Res A. 2014;102(8):2625–35.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Zhao Y, Xing Q, Janjanam J, et al. Facile electrochemical synthesis of antimicrobial TiO2 nanotube arrays. Int J Nanomedicine. 2014;9:5177–87.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Pauksch L, Hartmann S, Rohnke M, et al. Biocompatibility of silver nanoparticles and silver ions in primary human mesenchymal stem cells and osteoblasts. Acta Biomater. 2014;10(1):439–49.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Sengstock C, Diendorf J, Epple M, et al. Effect of silver nanoparticles on human mesenchymal stem cell differentiation. Beilstein J Nanotechnol. 2014;5:2058–69.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Necula BS, van Leeuwen JP, Fratila-Apachitei LE, et al. In vitro cytotoxicity evaluation of porous TiO2-Ag antibacterial coatings for human fetal osteoblasts. Acta Biomater. 2012;8(11):4191–7.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Greulich C, Kittler S, Epple M, et al. Studies on the biocompatibility and the interaction of silver nanoparticles with human mesenchymal stem cells (hMSCs). Langenbecks Arch Surg. 2009;394(3):495–502.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Ning C, Wang X, Li L, et al. Concentration ranges of antibacterial cations for showing the highest antibacterial efficacy but the least cytotoxicity against mammalian cells: implications for a new antibacterial mechanism. Chem Res Toxicol. 2015;28(9):1815–22.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Kraft CN, Hansis M, Arens S, et al. Striated muscle microvascular response to silver implants: a comparative in vivo study with titanium and stainless steel. J Biomed Mater Res. 2000;49(2):192–9.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Welz C Osteointegrative eigenschaften einer silberbeschichtung von hüftendoprothesen bei hunden. Dissertation. Westfälische Wilhelms Universität Münster; 2008.Google Scholar
  111. 111.
    Kabata T, Maeda T, Kajino Y, et al. Iodine-supported hip implants: short term clinical results. Biomed Res Int. 2015;2015:368124.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Demura S, Murakami H, Shirai T, et al. Surgical treatment for pyogenic vertebral osteomyelitis using iodine-supported spinal instruments: initial case series of 14 patients. Eur J Clin Microbiol Infect Dis. 2015;34(2):261–6.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Shirai T, Tsuchiya H, Nishida H, et al. Antimicrobial megaprostheses supported with iodine. J Biomater Appl. 2014;29(4):617–23.PubMedCrossRefGoogle Scholar
  114. 114.
    Tsuchiya H, Shirai T, Nishida H, et al. Innovative antimicrobial coating of titanium implants with iodine. J Orthop Sci. 2012;17(5):595–604.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Tennent DJ, Shiels SM, Sanchez CJ Jr, et al. Time-dependent effectiveness of locally applied vancomycin powder in a contaminated traumatic orthopaedic wound model. J Orthop Trauma. 2016;30(10):531–7.PubMedCrossRefGoogle Scholar
  116. 116.
    Armaghani SJ, Menge TJ, Lovejoy SA, et al. Safety of topical vancomycin for pediatric spinal deformity: nontoxic serum levels with supratherapeutic drain levels. Spine (Phila Pa 1976). 2014;39(20):1683–7.CrossRefGoogle Scholar
  117. 117.
    Khan NR, Thompson CJ, DeCuypere M, et al. A meta-analysis of spinal surgical site infection and vancomycin powder. J Neurosurg Spine. 2014;21(6):974–83.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Kang DG, Holekamp TF, Wagner SC, et al. Intrasite vancomycin powder for the prevention of surgical site infection in spine surgery: a systematic literature review. Spine J. 2015;15(4):762–70.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 119.
    Chiang HY, Herwaldt LA, Blevins AE, et al. Effectiveness of local vancomycin powder to decrease surgical site infections: a meta-analysis. Spine J. 2014;14(3):397–407.PubMedCrossRefGoogle Scholar
  120. 120.
    Tubaki VR, Rajasekaran S, Shetty AP. Effects of using intravenous antibiotic only versus local intrawound vancomycin antibiotic powder application in addition to intravenous antibiotics on postoperative infection in spine surgery in 907 patients. Spine (Phila Pa 1976). 2013;38(25):2149–55.CrossRefGoogle Scholar
  121. 121.
    Whiteside LA, Roy ME. One-stage revision with catheter infusion of intraarticular antibiotics successfully treats infected THA. Clin Orthop Relat Res. 2017;475(2):419–29.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Lawing CR, Lin FC, Dahners LE. Local injection of aminoglycosides for prophylaxis against infection in open fractures. J Bone Joint Surg Am. 2015;97(22):1844–51.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Giavaresi G, Meani E, Sartori M, et al. Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant. Int Orthop. 2014;38(7):1505–12.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Malizos K, Blauth M, Danita A, et al. Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: a multicenter randomized controlled trial. J Orthop Traumatol. 2017;18(2):159–69.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Penn-Barwell JG, Murray CK, Wenke JC. Local antibiotic delivery by a bioabsorbable gel is superior to PMMA bead depot in reducing infection in an open fracture model. J Orthop Trauma. 2014;28(6):370–5.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Bennett-Guerrero E, Berry SM, Bergese SD, et al. A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery. Am J Surg. 2017;213(6):1003–9.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Jennings JA, Carpenter DP, Troxel KS, et al. Novel antibiotic-loaded point-of-care implant coating inhibits biofilm. Clin Orthop Relat Res. 2015;473(7):2270–82.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Jennings JA, Beenken KE, Skinner RA, et al. Antibiotic-loaded phosphatidylcholine inhibits staphylococcal bone infection. World J Orthop. 2016;7(8):467–74.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Hesse W. Walther, Angelina Hesse-Early Contributors to Bacteriology. ASM News. 1992;58(8):425–8.Google Scholar
  130. 130.
    Kinnari TJ, Peltonen LI, Kuusela P, et al. Bacterial adherence to titanium surface coated with human serum albumin. Otol Neurotol. 2005;26(3):380–4.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Incani V, Omar A, Prosperi-Porta G, et al. Ag5IO6: novel antibiofilm activity of a silver compound with application to medical devices. Int J Antimicrob Agents. 2015;45(6):586–93.PubMedCrossRefGoogle Scholar
  132. 132.
    ASTM International. Standard test method for testing disinfectant efficacy against Pseudomonas aeruginosa biofilm using the MBEC assay. E2799-11. West Conshohocken, PA; 2011.Google Scholar
  133. 133.
    Melcher GA, Claudi B, Schlegel U, et al. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. J Bone Joint Surg Br. 1994;76(6):955–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Lambe DW Jr, Ferguson KP, Mayberry-Carson KJ, et al. Foreign-body-associated experimental osteomyelitis induced with Bacteroides fragilis and Staphylococcus epidermidis in rabbits. Clin Orthop Relat Res. 1991;266:285–94.Google Scholar
  135. 135.
    Williams DL, Haymond BS, Woodbury KL, et al. Experimental model of biofilm implant-related osteomyelitis to test combination biomaterials using biofilms as initial inocula. J Biomed Mater Res A. 2012;100(7):1888–900.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Williams DL, Costerton JW. Using biofilms as initial inocula in animal models of biofilm-related infections. J Biomed Mater Res B Appl Biomater. 2012;100(4):1163–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.DePuy Synthes Biomaterials R&DWest ChesterUSA

Personalised recommendations