title: Development of an animal model for Aggregatibacter actinomycetemcomitans biofilm-mediated oral osteolytic infection: a preliminary study.
abstract: BACKGROUND
  Biofilm-induced inflammatory osteolytic oral infections, such as periodontitis and peri-implantitis, have complex etiology and pathogenesis. A significant obstacle to research has been the lack of appropriate animal models where the inflammatory response to biofilms can be investigated. The aim of this study is to develop a novel animal model to study the host response to Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans)-biofilm colonizing titanium implants.
  
  
  METHODS
  Titanium implants were inoculated in vitro with A. actinomycetemcomitans, establishing a biofilm for 1 to 3 days. Biofilm-inoculated and control implants were transmucosally placed into rat hard palate or alveolar ridge. Analysis included documentation of clinical inflammation, polymerase chain reaction, and culture detection of A. actinomycetemcomitans and microcomputed tomography quantitation of peri-implant bone volume.
  
  
  RESULTS
  Viable A. actinomycetemcomitans biofilm was successfully established on titanium implants in vitro, detected by confocal laser scanning microscopy. An inflammatory response characterized by clinical inflammation, bleeding, ulceration, hyperplasia, and necrosis was observed around biofilm-inoculated implants. A. actinomycetemcomitans was detected by polymerase chain reaction and culture analysis on 100% of biofilm-inoculated implants for up to 3 weeks and 25% for up to 6 weeks. Microcomputed tomography analysis demonstrated significantly lower bone volume (P <0.05) around biofilm-inoculated implants (29.6% ± 7.6%) compared to non-inoculated implants (50.5% ± 9.6%) after 6 weeks.
  
  
  CONCLUSIONS
  These results describe a novel animal model where A. actinomycetemcomitans biofilm was established in vitro on titanium implants before placement in rat oral cavity, leading to an inflammatory response, osteolysis, and tissue destruction. This model may have potential use for investigation of host responses to biofilm pathogens and antibiofilm therapy.
authors.affiliation: Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Freire
authors.forename: Parish P
authors.initials: PP
authors.lastname: Sedghizadeh
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaudinn
authors.forename: Amita
authors.initials: A
authors.lastname: Gorur
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Downey
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Weizhen
authors.initials: W
authors.lastname: Chen
authors.forename: Joong-Ki
authors.initials: JK
authors.lastname: Kook
authors.forename: Casey
authors.initials: C
authors.lastname: Chen
authors.forename: Steven D
authors.initials: SD
authors.lastname: Goodman
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
mesh_terms: D000189:Actinobacillus Infections / Q000382:microbiology*; D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology*; D016301:Alveolar Bone Loss / Q000382:microbiology; D000539:Alveolar Process / Q000382:microbiology / Q000601:surgery; D000818:Animals; D001422:Bacterial Adhesion; D001431:Bacteriological Techniques; D018441:Biofilms; D015921:Dental Implants / Q000382:microbiology; D003764:Dental Materials / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005884:Gingival Hemorrhage / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006965:Hyperplasia; D050296:Microbial Viability; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009336:Necrosis; D019226:Oral Ulcer / Q000382:microbiology; D021362:Palate, Hard / Q000601:surgery; D057873:Peri-Implantitis / Q000382:microbiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D015921:Dental Implants; D003764:Dental Materials; D014025:Titanium