Skip to main content
SpringerLink
Log in
Book cover

A Modern Approach to Biofilm-Related Orthopaedic Implant Infections pp 29–50Cite as

Animal Models of Implant-Related Low-Grade Infections. A Twenty-Year Review

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AMIDPH,volume 971))

Abstract

The demand for joint replacement and surgical treatment is continuously increasing, thus representing a clinical burden and a cost for the healthcare system. Among several pathogens involved in implant-related infections, staphylococci account for the two-thirds of clinically isolated bacteria. Despite most of them are highly virulent microorganisms (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa), low virulent bacteria (Staphylococcus epidermidis, Propionibacterium acnes) are responsible for delayed, low-grade infections without specific clinical signs and hardly distinguishable from aseptic prosthetic failure. Therefore, there is a real need to study the pathogenesis of orthopedic infections through in vivo animal models. The present review of the literature provides a 20-year overview of animal models of acute, subclinical or chronic orthopedic infections according to the pathogen virulence and inocula. Through this analysis, a great variety of conditions in terms of bacterial strains and inocula emerged, thus encouraging the development of more reproducible in vivo studies to provide relevant information for a translational approach to humans.

Authors Contribution: Arianna Barbara Lovati and Marta Bottagisio contributed equally with all other contributors.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

CFU:

colony forming unit

MRSA:

methicillin-resistant S. aureus

MRSE:

methicillin-resistant S. epidermidis

IL:

interleukin

MCP-1:

monocyte chemoattractant protein-1

MDSC:

myeloid-derived suppressor cells

Ag+ :

silver ions

HA:

hydroxyapatite

K-wire:

Kirschner wire

References

  • Achermann Y, Tran B, Kang M et al (2015) Immunoproteomic identification of in vivo-produced propionibacterium acnes proteins in a rabbit biofilm infection model. Clin Vaccine Immunol 22:467–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Adams CS, Antoci V Jr, Harrison G et al (2009) Controlled release of vancomycin from thin sol–gel films on implant surfaces successfully controls osteomyelitis. J Orthop Res 27:701–709

    Article  CAS  PubMed  Google Scholar 

  • Akiyama T, Miyamoto H, Yonekura Y et al (2013) Silver oxide-containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia. J Orthop Res 31:1195–1200

    Article  CAS  PubMed  Google Scholar 

  • Antoci V Jr, Adams CS, Hickok NJ et al (2007) Vancomycin bound to Ti rods reduces periprosthetic infection: preliminary study. Clin Orthop Relat Res 461:88–95

    PubMed  Google Scholar 

  • Arciola CR, Campoccia D, Ehrlich GD et al (2015) Biofilm-based implant infections in orthopaedics. Adv Exp Med Biol 830:29–46

    Article  PubMed  Google Scholar 

  • Arens D, Wilke M, Calabro L et al (2015) A rabbit humerus model of plating and nailing osteosynthesis with and without Staphylococcus aureus osteomyelitis. Eur Cell Mater 30:148–161

    Article  CAS  PubMed  Google Scholar 

  • Bernthal NM, Stavrakis AI, Billi F et al (2010) A mouse model of post-arthroplasty Staphylococcus aureus joint infection to evaluate in vivo the efficacy of antimicrobial implant coatings. PLoS One 5:e12580

    Article  PubMed  PubMed Central  Google Scholar 

  • Brady RA, Mocca CP, Prabhakara R et al (2013) Evaluation of genetically inactivated alpha toxin for protection in multiple mouse models of Staphylococcus aureus infection. PLoS One 8:e63040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campoccia D, Montanaro L, Arciola CR (2005) The significance of infection related to orthopaedic devices and issues of antibiotic resistance. Biomaterials 27:2331–2339

    Article  PubMed  Google Scholar 

  • Cevher E, Orhan Z, Sensoy D et al (2007) Sodium fusidate-poly(D, L-lactide-co-glycolide) microspheres: preparation, characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis. J Microencapsul 24:577–595

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Tsukayama DT, Kidder LS et al (2005) Characterization of a chronic infection in an internally-stabilized segmental defect in the rat femur. J Orthop Res 23:816–823

    Article  PubMed  Google Scholar 

  • Craig MR, Poelstra KA, Sherrell JC et al (2005) A novel total knee arthroplasty infection model in rabbits. J Orthop Res 23:1100–1104

    Article  PubMed  Google Scholar 

  • Darouiche RO, Mansouri MD, Zakarevicz D et al (2007) In vivo efficacy of antimicrobial-coated devices. J Bone Joint Surg Am 89:792–797

    PubMed  Google Scholar 

  • Del Pozo JL, Rouse MS, Euba G et al (2009) The electricidal effect is active in an experimental model of Staphylococcus epidermidis chronic foreign body osteomyelitis. Antimicrob Agents Chemother 53:4064–4068

    Article  PubMed  PubMed Central  Google Scholar 

  • Drago L, De Vecchi E, Cappelletti L et al (2015) Prolonging culture to 15 days improves bacterial detection in bone and joint infections. Eur J Clin Microbiol Infect Dis 34:1809–1813

    Article  CAS  PubMed  Google Scholar 

  • Ensrud KE (2013) Epidemiology of fracture risk with advancing age. J Gerontol A Biol Sci Med Sci 68:1236–1242

    Article  PubMed  Google Scholar 

  • Fölsch C, Federmann M, Kuehn KD et al (2015) Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model. Int Orthop 39:981–988

    Article  PubMed  Google Scholar 

  • Fukushima N, Yokoyama K, Sasahara T et al (2005) Establishment of rat model of acute staphylococcal osteomyelitis: relationship between inoculation dose and development of osteomyelitis. Arch Orthop Trauma Surg 125:169–176

    Article  PubMed  Google Scholar 

  • Haenle M, Zietz C, Lindner T et al (2013) A model of implant-associated infection in the tibial metaphysis of rats. ScientificWorldJournal 2013:481975

    Article  PubMed  PubMed Central  Google Scholar 

  • Harrasser N, Gorkotte J, Obermeier A et al (2016) A new model of implant-related osteomyelitis in the metaphysis of rat tibiae. BMC Musculoskelet Disord 17:152

    Article  PubMed  PubMed Central  Google Scholar 

  • Heim CE, Vidlak D, Scherr TD et al (2014) Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J Immunol 192:3778–3792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heim CE, Vidlak D, Scherr TD et al (2015) IL-12 promotes myeloid-derived suppressor cell recruitment and bacterial persistence during Staphylococcus aureus orthopedic implant infection. J Immunol 194:3861–3872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helbig L, Guehring T, Rosenberger S et al (2015) A new animal model for delayed osseous union secondary to osteitis. BMC Musculoskelet Disord 16:362

    Article  PubMed  PubMed Central  Google Scholar 

  • Kose N, Otuzbir A, Pekşen C et al (2013) A silver ion-doped calcium phosphate-based ceramic nanopowder-coated prosthesis increased infection resistance. Clin Orthop Relat Res 471:2532–2539

    Article  PubMed  PubMed Central  Google Scholar 

  • Kraft CN, Schlegel U, Pfluger D et al (2001) Radiological signs of osteitis around extramedullary metal implants. A radiographic-microbiological correlative analysis in rabbit tibiae after local inoculation of Staphylococcus aureus. Arch Orthop Trauma Surg 121:338–342

    Article  CAS  PubMed  Google Scholar 

  • Li B, Jiang B, Dietz MJ et al (2010) Evaluation of local MCP-1 and IL-12 nanocoatings for infection prevention in open fractures. J Orthop Res 28:48–54

    Article  CAS  PubMed  Google Scholar 

  • Lindsey BA, Clovis NB, Smith ES et al (2010a) An animal model for open femur fracture and osteomyelitis: Part I. J Orthop Res 28:38–42

    PubMed  Google Scholar 

  • Lindsey BA, Clovis NB, Smith ES et al (2010b) An animal model for open femur fracture and osteomyelitis-Part II: immunomodulation with systemic IL-12. J Orthop Res 28:43–47

    CAS  PubMed  Google Scholar 

  • Lovati AB, Drago L, Monti L et al (2013) Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection. PLoS One 8:e67628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lovati AB, Romanò CL, Monti L et al (2014) Does PGE1 vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model. PLoS One 9:e94758

    Article  PubMed  PubMed Central  Google Scholar 

  • Lovati AB, Romanò CL, Bottagisio M et al (2016) Modeling staphylococcus epidermidis-induced non-unions: subclinical and clinical evidence in rats. PLoS One 11:e0147447

    Article  PubMed  PubMed Central  Google Scholar 

  • Lucke M, Schmidmaier G, Sadoni S et al (2003a) A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater 67:593–602

    Article  CAS  PubMed  Google Scholar 

  • Lucke M, Schmidmaier G, Sadoni S et al (2003b) Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone 32:521–531

    Article  CAS  PubMed  Google Scholar 

  • Lucke M, Wildemann B, Sadoni S et al (2005) Systemic versus local application of gentamicin in prophylaxis of implant-related osteomyelitis in a rat model. Bone 36:770–778

    Article  CAS  PubMed  Google Scholar 

  • Marriott I, Gray DL, Tranguch SL et al (2004) Osteoblasts express the inflammatory cytokine interleukin-6 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Am J Pathol 164:1399–1406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marriott I, Gray DL, Rati DM et al (2005) Osteoblasts produce monocyte chemoattractant protein-1 in a murine model of Staphylococcus aureus osteomyelitis and infected human bone tissue. Bone 37:504–512

    Article  CAS  PubMed  Google Scholar 

  • Mecikoglu M, Saygi B, Yildirim Y et al (2006) The effect of proteolytic enzyme serratiopeptidase in the treatment of experimental implant-related infection. J Bone Joint Surg Am 88:1208–1214

    PubMed  Google Scholar 

  • Oh SH, Nam BR, Lee IS et al (2016a) Prolonged anti-bacterial activity of ion-complexed doxycycline for the treatment of osteomyelitis. Eur J Pharm Biopharm 98:67–75

    Article  CAS  PubMed  Google Scholar 

  • Oh EJ, Oh SH, Lee IS et al (2016b) Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis. J Biomater Appl 30:1534–1544

    Article  CAS  PubMed  Google Scholar 

  • Pesanti EL, Lorenzo JA (1998) Osteoclasts and effects of interleukin 4 in development of chronic osteomyelitis. Clin Orthop Relat Res 355:290–299

    Article  Google Scholar 

  • Phillips JE, Crane TP, Noy M et al (2006) The incidence of deep prosthetic infections in a specialist orthopaedic hospital: a 15-year prospective survey. J Bone Joint Surg (Br) 88:943–948

    Article  CAS  Google Scholar 

  • Portillo ME, Corvec S, Borens O et al (2013) Propionibacterium acnes: an underestimated pathogen in implant-associated infections. Biomed Res Int 2013:804391

    Article  PubMed  PubMed Central  Google Scholar 

  • Pribaz JR, Bernthal NM, Billi F et al (2012) Mouse model of chronic post-arthroplasty infection: noninvasive in vivo bioluminescence imaging to monitor bacterial burden for long-term study. J Orthop Res 30:335–340

    Article  PubMed  Google Scholar 

  • Ribeiro M, Monteiro FJ, Ferraz MP (2012) Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions. Biomatter 2:176–194

    Article  PubMed  PubMed Central  Google Scholar 

  • Sanchez CJ Jr, Prieto EM, Krueger CA et al (2013) Effects of local delivery of D-amino acids from biofilm-dispersive scaffolds on infection in contaminated rat segmental defects. Biomaterials 34:7533–7543

    Article  CAS  PubMed  Google Scholar 

  • Saper D, Capiro N, Ma R et al (2015) Management of Propionibacterium acnes infection after shoulder surgery. Curr Rev Musculoskelet Med 8:67–74

    Article  PubMed  PubMed Central  Google Scholar 

  • Sener M, Kazimoglu C, Karapinar H et al (2010) Comparison of various surgical methods in the treatment of implant-related infection. Int Orthop 34:419–423

    Article  PubMed  Google Scholar 

  • Sheehan E, McKenna J, Mulhall KJ et al (2004) Adhesion of Staphylococcus to orthopaedic metals, an in vivo study. J Orthop Res 22:39–43

    Article  CAS  PubMed  Google Scholar 

  • Smeltzer MS, Thomas JR, Hickmon SG et al (1997) Characterization of a rabbit model of staphylococcal osteomyelitis. J Orthop Res 15:414–421

    Article  CAS  PubMed  Google Scholar 

  • Søe NH, Jensen NV, Nürnberg BM et al (2013) A novel knee prosthesis model of implant-related osteomyelitis in rats. Acta Orthop 84:92–97

    Article  PubMed  PubMed Central  Google Scholar 

  • Song Z, Borgwardt L, Høiby N et al (2013) Prosthesis infections after orthopedic joint replacement: the possible role of bacterial biofilms. Orthop Rev (Pavia) 5:65–71

    Article  Google Scholar 

  • Tatara AM, Shah SR, Livingston CE et al (2015) Infected animal models for tissue engineering. Methods 84:17–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trampuz A, Widmer AF (2006) Infections associated with orthopedic implants. Curr Opin Infect Dis 19:349–356

    Article  CAS  PubMed  Google Scholar 

  • van der Borden AJ, Maathuis PG, Engels E et al (2007) Prevention of pin tract infection in external stainless steel fixator frames using electric current in a goat model. Biomaterials 28:2122–2126

    Article  PubMed  Google Scholar 

  • Wagner JM, Zöllner H, Wallner C et al (2016) Surgical debridement is superior to sole antibiotic therapy in a novel murine posttraumatic osteomyelitis model. PLoS One 11:e0149389

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang CJ, Li Q, Wu GC et al (2012) A practical model of osteomyelitis-induced bone pain by intra-tibial injection of Staphylococcus aureus in rats. Neurosci Lett 513:198–203

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of Interests

The authors declare that there is not conflict of interests regarding the publication of this paper.

Author information

Author notes

    Authors and Affiliations

    1. Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopedic Institute, via R. Galeazzi 4, 20161, Milan, Italy

      Arianna Barbara Lovati & Marta Bottagisio

    2. Department of Veterinary Medicine, University of Milan, via Celoria 10, 20133, Milan, Italy

      Marta Bottagisio

    3. Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi Orthopedic Institute, via R. Galeazzi 4, 20161, Milan, Italy

      Elena de Vecchi & Lorenzo Drago

    4. Department of Reconstructive Surgery of Osteo-articular Infections C.R.I.O. Unit, IRCCS Galeazzi Orthopedic Institute, via R. Galeazzi 4, 20161, Milan, Italy

      Enrico Gallazzi

    5. Department of Biomedical Science for Health, University of Milan, via L. Mangiagalli 31, 20133, Milan, Italy

      Lorenzo Drago

    Authors
    1. Arianna Barbara Lovati
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Marta Bottagisio
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Elena de Vecchi
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Enrico Gallazzi
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Lorenzo Drago
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Arianna Barbara Lovati .

    Editor information

    Editors and Affiliations

    1. Department of Biomedical Sciences Health, University of Milan, Milan, Italy

      Lorenzo Drago

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2016 Springer International Publishing Switzerland

    About this chapter

    Cite this chapter

    Lovati, A.B., Bottagisio, M., de Vecchi, E., Gallazzi, E., Drago, L. (2016). Animal Models of Implant-Related Low-Grade Infections. A Twenty-Year Review. In: Drago, L. (eds) A Modern Approach to Biofilm-Related Orthopaedic Implant Infections. Advances in Experimental Medicine and Biology(), vol 971. Springer, Cham. https://doi.org/10.1007/5584_2016_157

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation