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.

Design, Synthesis, and Antimicrobial Evaluation of a Novel Bone-Targeting Bisphosphonate-Ciprofloxacin Conjugate for the Treatment of Osteomyelitis Biofilms

“…This model allows standardized and reproducible quantities of viable bacteria to be formed as well-established biofilms on each implant, which we have previously demonstrated persists in vivo for several weeks after placement and causes infection, inflammation, and bone destruction locally. 31 …”

Enhanced Probiotic Potential of Lactobacillus reuteri When Delivered as a Biofilm on Dextranomer Microspheres That Contain Beneficial Cargo

“…We have demonstrated in previous work with the dental pathogen Aggregatibacter actinomycetemcomitans , that challenging a host with an already-established pathogenic biofilm results in greater ability of the pathogen to establish disease in an animal model of oral infection (Freire et al, 2011, 2017). While it is clear that being bound to DMs offers multiple advantages in terms of survivability and relative adherence to an epithelial target cell, the actual state of the DM-adhered L. reuteri and its phenotype has yet to be determined.…”

Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD‐Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri‐Implantitis

“…Aa , or organisms likely to be Aa , have been isolated in high numbers from young patients with rapidly progressing alveolar bone breakdown . It has been shown that Aa can form a biofilm on titanium implants, which can in turn be used as a colonizing surface, allowing in vivo bacterial persistence and inflammatory host response . In addition, inflammatory cells, with B‐lymphocytes and plasma cells being the most dominant among them, infiltrate the connective tissue adjacent to the pocket epithelium.…”