(63) Immunomodulatory Strategies using local Sustained delivery to prevent inflammatory bone loss in Peri-implantitis: Murine Model

Introduction: Peri-implantitis is an inflammatory condition of the soft tissues and bone around dental implants, which leads to bone destruction and can eventually lead to implant loss. There is some evidence of the shared pathogenesis of peri-implantitis (PI) with periodontitis (PD), as far as etiology and host immune response are concerned. Both diseases are initiated by the bacterial biofilm and share similar cellular inflammatory infiltrate composition. However, PI lesions often present a significantly larger number of plasma cells, macrophages, and neutrophils, than periodontitis lesions. Today, there is no standardized treatment protocol for peri-implantitis. Current treatment options for peri-implantitis, are directed towards surgical intervention. This includes decontaminations of the surface of the implant from the existing bacterial biofilm using painful, time-intensive, mechanical scrubbing, laser treatments, open gum-flap surgery, and often replacement of the dental implant. Studies by our group have shown that local delivery of IL-4 or CCL2 prevents ligature induced periodontitis by inhibiting the production of proinflammatory and osteoclastogenic mediators, such as IL-1, and TNF-a in periodontitis. Considering similar pathophysiology between the two diseases (PI and PD), a similar outcome could be postulated if CCL2 or IL4 were to be used in the prevention of peri-implantitis. The objective of this study was to develop an experimental peri-implantitis preventive murine model using local sustained delivery of CCL2 or IL4 to reduce local bone loss around implants during bacterial infection.

Methods: Male BALB/c wild type mice aged 6-8 weeks old were used in the study. The first second and third molars were extracted, and the sites were allowed to heal for 8 weeks. Each mouse received machined, smooth-surface, screw-shaped titanium implants (1mm) in the healed alveolar bone between 1st and 2nd maxillary molars,8 weeks after tooth extraction. The mice were divided into five groups: local sustained delivery of CCL2, IL4, ‘blank’ particles, untreated and healthy control. 4 weeks after osteointegration, periimplantitis was developed by tying a 6-0 silk ligature model around the dental implant. The healthy control group did not receive any silk ligature around the implant whereas the untreated control received the silk ligature without delivery of neither CCL2 nor IL4. Mice were sacrificed at 1 week, period after peri-implantitis induction. Implant survival and peri-implant bone levels were analyzed by micro-computed tomography (micro-CT) scans.

Results: Our preliminary data shows greater bone loss around the implants that received ligatures (untreated) and blank particles vs those given CCL2 or IL4 when analyzed by micro-CT. This analysis is ongoing and more data will be presented.

Conclusions: We have preliminary data demonstrating that this preventative, local and sustained delivery of CCL2 or IL-4, decreases alveolar bone loss in mice. This study establishes a proof of concept that host immune modulation is a promising therapeutic tool to be used to prevent bone loss around dental implants with periimplantitis. This model opens avenues for further available treatment options for early signs of peri-implantitis without the use of the surgical intervention.

Lead Author’s Contributions to the Research Project: The lead author contributed towards this study by conducting the animal extraction, implant placement and follow-up post-surgery. Assisted in the Micro-CT analysis. She will continue in data analysis.