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A new rabbit model of implant-related biofilm infection: development and evaluation

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Abstract

This study is to establish a rabbit model for human prosthetic joint infection and biofilm formation. Thirty-two healthy adult rabbits were randomly divided into four groups and implanted with stainless steel screws and ultra-high molecular weight polyethylene (UHMWPE) washers in the non-articular surface of the femoral lateral condyle of the right hind knees. The rabbit knee joints were inoculated with 1 mL saline containing 0, 102, 103, 104 CFU of Staphylococcus epidermidis (S. epidermidis) isolated from the patient with total knee arthroplasty (TKA) infection, respectively. On the 14th postoperative day, the UHMWPE washers from the optimal 103 CFU group were further examined. The SEM examination showed a typical biofilm construction that circular S. epidermidis were embedded in a mucous-like matrix. In addition, the LCSM examination showed that the biofilm consisted of the polysaccharide stained bright green fluorescence and S. epidermidis radiating red fluorescence. Thus, we successfully create a rabbit model for prosthetic joint infection and biofilm formation, which should be valuable for biofilm studies.

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References

  1. Kurtz S M, Lau E, Watson H, et al. Economic burden of periprosthetic joint infection in the United States. The Journal of Arthroplasty, 2012, 27(8 Suppl): 61–65

    Article  Google Scholar 

  2. Haenle M, Skripitz C, Mittelmeier W, et al. Economic impact of infected total hip arthroplasty in the German diagnosis-related groups system. Der Orthopade, 2012, 41(6): 467–476

    Article  Google Scholar 

  3. Haenle M, Skripitz C, Mittelmeier W, et al. Economic impact of infected total knee arthroplasty. The Scientific World Journal, 2012, (1): 196515

    Google Scholar 

  4. Kurtz S M, Lau E, Schmier J, et al. Infection burden for hip and knee arthroplasty in the United States. The Journal of Arthroplasty, 2008, 23(7): 984–991

    Article  Google Scholar 

  5. Del Pozo J L, Patel R. Clinical practice. Infection associated with prosthetic joints. The New England Journal of Medicine, 2009, 361(8): 787–794

    Article  Google Scholar 

  6. Phillips J E, Crane T P, Noy M, et al. The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. The Journal of Bone and Joint Surgery (British Volume), 2006, 88B(7): 943–948

    Article  Google Scholar 

  7. Pulido L, Ghanem E, Joshi A, et al. Periprosthetic joint infection: the incidence, timing, and predisposing factors. Clinical Orthopaedics and Related Research, 2008, 466(7): 1710–1715

    Article  Google Scholar 

  8. Jämsen E, Varonen M, Huhtala H, et al. Incidence of prosthetic joint infections after primary knee arthroplasty. The Journal of Arthroplasty, 2010, 25(1): 87–92

    Article  Google Scholar 

  9. Kurtz S, Ong K, Lau E, et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. The Journal of Bone and Joint Surgery (American Volume), 2007, 89(4): 780–785

    Article  Google Scholar 

  10. Kurtz S M, Lau E, Schmier J, et al. Infection burden for hip and knee arthroplasty in the United States. The Journal of Arthroplasty, 2008, 23(7): 984–991

    Article  Google Scholar 

  11. Vuong C, Otto M. Staphylococcus epidermidis infections. Microbes and Infection, 2002, 4(4): 481–489

    Article  Google Scholar 

  12. Zimmerli W, Trampuz A, Ochsner P E. Prosthetic-joint infections. The New England Journal of Medicine, 2004, 351(16): 1645–1654

    Article  Google Scholar 

  13. Costerton W, Veeh R, Shirtliff M, et al. The application of biofilm science to the study and control of chronic bacterial infections. Journal of Clinical Investigation, 2003, 112(10): 1466–1477

    Article  Google Scholar 

  14. Høiby N, Ciofu O, Johansen H K, et al. The clinical impact of bacterial biofilms. International Journal of Oral Science, 2011, 3 (2): 55–65

    Article  Google Scholar 

  15. Percival S L, Hill K E, Malic S, et al. Antimicrobial tolerance and the significance of persister cells in recalcitrant chronic wound biofilms. Wound Repair and Regeneration, 2011, 19(1): 1–9

    Article  Google Scholar 

  16. Srinivasan A, Uppuluri P, Lopez-Ribot J, et al. Development of a high-throughput Candida albicans biofilm chip. PLoS ONE, 2011, 6(4): e19036

    Google Scholar 

  17. Zimmerli W, Moser C. Pathogenesis and treatment concepts of orthopaedic biofilm infections. FEMS Immunology and Medical Microbiology, 2012, 65(2): 158–168

    Article  Google Scholar 

  18. Geipel U. Pathogenic organisms in hip joint infections. International Journal of Medical Sciences, 2009, 6(5): 234–240

    Article  Google Scholar 

  19. Pandey R, Berendt A R, Athanasou N A. Histological and microbiological findings in non-infected and infected revision arthroplasty tissues. Archives of Orthopaedic and Trauma Surgery, 2000, 120(10): 570–574

    Article  Google Scholar 

  20. Talsma S S. Biofilms on medical devices. Home Healthcare Nurse, 2007, 25(9): 589–594

    Article  Google Scholar 

  21. Otto M. Staphylococcal biofilms. Current Topics in Microbiology and Immunology, 2008, 322: 207–228

    Google Scholar 

  22. Otto M. Staphylococcus epidermidis—the ‘accidental’ pathogen. Nature Reviews: Microbiology, 2009, 7(8): 555–567

    Google Scholar 

  23. Pribaz J R, Bernthal N M, Billi F, et al. Mouse model of chronic post-arthroplasty infection: noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long-term study. Journal of Orthopaedic Research, 2012, 30(3): 335–340

    Article  Google Scholar 

  24. Scherr T D, Lindgren K E, Schaeffer C R, et al. Mouse model of post-arthroplasty Staphylococcus epidermidis joint infection. Methods in Molecular Biology, 2014, 1106: 173–181

    Article  Google Scholar 

  25. Søe N H, Jensen N V, Nürnberg B M, et al. A novel knee prosthesis model of implant-related osteomyelitis in rats. Acta Orthopaedica, 2013, 84(1): 92–97

    Article  Google Scholar 

  26. Bernthal N M, Stavrakis A I, Billi F, et al. A mouse model of postarthroplasty Staphylococcus aureus joint infection to evaluate in vivo the efficacy of antimicrobial implant coatings. PLoS ONE, 2010, 5(9): e12580

    Google Scholar 

  27. Belmatoug N, Crémieux A C, Bleton R, et al. A new model of experimental prosthetic joint infection due to methicillin-resistant Staphylococcus aureus: a microbiologic, histopathologic, and magnetic resonance imaging characterization. The Journal of Infectious Diseases, 1996, 174(2): 414–417

    Article  Google Scholar 

  28. Lucke M, Schmidmaier G, Sadoni S, et al. A new model of implant-related osteomyelitis in rats. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2003, 67B(1): 593–602

    Article  Google Scholar 

  29. Craig M R, Poelstra K A, Sherrell J C, et al. A novel total knee arthroplasty infection model in rabbits. Journal of Orthopaedic Research, 2005, 23(5): 1100–1104

    Article  Google Scholar 

  30. Isenberg H D. Clinical Microbiology Procedure Handbook. 1st ed. Washington, DC: American Society for Microbiology, 1992

    Google Scholar 

  31. Steckelberg J M, Osmon D R. Prosthetic joint infection. In: Waldvogel F A, ed. Infections Associated with Indwelling Medical Devices. 3rd ed. Washington, DC: ASM Press, 2000, 173–205

    Google Scholar 

  32. Montanaro L, Speziale P, Campoccia D, et al. Scenery of Staphylococcus implant infections in orthopedics. Future Microbiology, 2011, 6(11): 1329–1349

    Article  Google Scholar 

  33. Hellmark B, Söderquist B, Unemo M, et al. Comparison of Staphylococcus epidermidis isolated from prosthetic joint infections and commensal isolates in regard to antibiotic susceptibility, agr type, biofilm production, and epidemiology. International Journal of Medical Microbiology, 2013, 303(1): 32–39

    Article  Google Scholar 

  34. Chen-Charpentier B M, Stanescu D. Biofilm growth on medical implants with randomness. Mathematical and Computer Modelling, 2011, 54(7–8): 1682–1686

    Article  Google Scholar 

  35. Sendi P, Banderet F, Graber P, et al. Clinical comparison between exogenous and haematogenous periprosthetic joint infections caused by Staphylococcus aureus. Clinical Microbiology and Infection, 2011, 17(7): 1098–1100

    Article  Google Scholar 

  36. Berbari E F, Hanssen A D, Duffy M C, et al. Risk factors for prosthetic joint infection: case-control study. Clinical Infectious Diseases, 1998, 27(5): 1247–1254

    Article  Google Scholar 

  37. Zimmerli W, Sendi P. Pathogenesis of implant-associated infection: the role of the host. Seminars in Immunopathology, 2011, 33(3): 295–306

    Article  Google Scholar 

  38. Rodet A. Physiologie pathologique–étudeexpérimentalesurl’ostéomyeliteinfectieuse. C R Acad Sci, 1885, 99: 569–571

    Google Scholar 

  39. Zurexperimentellenerzeugungosteomyelitischerherde L E. Arch Klin Chir, 1894, 48: 181–200

    Google Scholar 

  40. Rissing J P, Buxton T B, Weinstein R S, et al. Model of experimental chronic osteomyelitis in rats. Infection & Immunity, 1985, 47(3): 581–586

    Google Scholar 

  41. Fukushima N, Yokoyama K, Sasahara T, et al. Establishment of rat model of acute staphylococcal osteomyelitis: relationship between inoculation dose and development of osteomyelitis. Archives of Orthopaedic & Trauma Surgery, 2005, 125(3): 169–176

    Article  Google Scholar 

  42. Ofluoglu E A, Zileli M, Aydin D, et al. Implant-related infection model in rat spine. Archives of Orthopaedic and Trauma Surgery, 2007, 127(5): 391–396

    Article  Google Scholar 

  43. Poultsides L A, Papatheodorou L K, Karachalios T S, et al. Novel model for studying hematogenous infection in an experimental setting of implant-related infection by a community-acquired methicillin-resistant S. aureus strain. Journal of Orthopaedic Research, 2008, 26(10): 1355–1362

    Article  Google Scholar 

  44. Vogelyl H C, Dhertl W J A, Fleer A, et al. The infected orthopaedic implant. An animal model to study the mechanisms of haematogenous infection of cementless implant materials. European Journal of Orthopaedic Surgery & Traumatology, 1996, 6(2): 91–95

    Article  Google Scholar 

  45. Boles B R, Horswill A R. Staphylococcal biofilm disassembly. Trends in Microbiology, 2011, 19(9): 449–455

    Article  Google Scholar 

  46. Mack D, Becker P, Chatterjee I, et al. Mechanisms of biofilm formation in Staphylococcus epidermidis and Staphylococcus aureus: functional molecules, regulatory circuits, and adaptive responses. International Journal of Medical Microbiology, 2004, 294(2–3): 203–212

    Article  Google Scholar 

  47. 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. The Journal of Bone and Joint Surgery (American Volume), 2012, 94 (15): 1406–1415

    Article  Google Scholar 

  48. Alt V, Lips K S, Henkenbehrens C, et al. A new animal model for implant-related infected non-unions after intramedullary fixation of the tibia in rats with fluorescent in situ hybridization of bacteria in bone infection. Bone, 2011, 48(5): 1146–1153

    Article  Google Scholar 

  49. Montanaro L, Poggi A, Visai L, et al. Extracellular DNA in biofilms. The International Journal of Artificial Organs, 2011, 34 (9): 824–831

    Article  Google Scholar 

  50. Cue D, Lei M G, Lee C Y. Genetic regulation of the intercellular adhesion locus in staphylococci. Frontiers in Cellular and Infection Microbiology, 2012, 2: 38

    Article  Google Scholar 

  51. Foster T J, Geoghegan J A, Ganesh V K, et al. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nature Reviews: Microbiology, 2013, 12 (1): 49–62

    Google Scholar 

  52. Stoodley P, Kathju S, Hu F Z, et al. Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections. Clinical Orthopaedics and Related Research, 2005, 437: 31–40

    Article  Google Scholar 

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Correspondence to Cheng-Bing Chu or Fu-Zhai Cui.

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Chu, CB., Zeng, H., Shen, DX. et al. A new rabbit model of implant-related biofilm infection: development and evaluation. Front. Mater. Sci. 10, 80–89 (2016). https://doi.org/10.1007/s11706-016-0324-1

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