title: A model of implant-associated infection in the tibial metaphysis of rats.
abstract: OBJECTIVE
  Implant-associated infections remain serious complications in orthopaedic and trauma surgery. A main scientific focus has thus been drawn to the development of anti-infective implant coatings. Animal models of implant-associated infections are considered helpful in the in vivo testing of new anti-infective implant coatings. The aim of the present study was to evaluate a novel animal model for generation of implant-associated infections in the tibial metaphysis of rats.
  
  
  METHODS
  A custom-made conical implant made of Ti6Al4V was inserted bilaterally at the medial proximal tibia of 26 female Sprague-Dawley rats. Staphylococcus aureus in amounts spanning four orders of magnitude and each suspended in 15  μ l phosphate buffered saline (PBS) was inoculated into the inner cavity of the implant after the implantation into the defined position. Controls were treated accordingly with PBS alone. Animals were then followed for six weeks until sacrifice. Implant-associated infection was evaluated by microbiological investigation using swabs and determination of viable bacteria in the bone around the implant and the biofilm on the implants after sonification.
  
  
  RESULTS
  Irrespective of the initial inoculum, all animals in the various groups harbored viable bacteria in the intraoperative swabs as well as the sonication fluid of the implant and the bone samples. No correlation could be established between initially inoculated CFU and population sizes on implant surfaces at sacrifice. However, a significantly higher viable count was observed from peri-implant bone samples for animals inoculated with 10(6) CFU. Macroscopic signs of animal infection (pus and abscess formation) were only observed for implants inoculated with at least 10(5) CFU S. aureus.
  
  
  CONCLUSIONS
  The results demonstrate the feasibility of this novel animal model to induce an implant-associated infection in the metaphysis of rats, even with comparatively low bacterial inocula. The specific design of the implant allows an application of bacteria in reproducible numbers at well-defined contact sites to the animal bone.
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Haenle
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Zietz
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Lindner
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, University Rostock, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Arndt
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Vetter
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Mittelmeier
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, University Rostock, Schillingallee 70, 18057 Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Podbielski
authors.affiliation: Department of Orthopaedics, University Medicine Rostock, Doberaner Straße 142, 18057 Rostock, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bader
mesh_terms: D000497:Alloys; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018441:Biofilms; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D005260:Female; D019736:Prostheses and Implants / Q000009:adverse effects* / Q000382:microbiology; D016459:Prosthesis-Related Infections / Q000209:etiology* / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013203:Staphylococcal Infections / Q000209:etiology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000254:growth & development; D013977:Tibia / Q000382:microbiology; D014025:Titanium
chemical_list: D000497:Alloys; D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; C031462:titanium alloy (TiAl6V4); D014025:Titanium