Breakdown of Periodontal Homeostasis by Dental Implants

Objectives: Peri-implantitis is a chronic inflammatory disease resulting in implant loss. To study the
mechanisms of this widespread disease, we developed a murine model of dental implants in order to study the immune response around titanium implants.
Methods: Mice received titanium implants four weeks after extraction of the right maxillary
molars and were sacrificed at 2, 4 and 10 weeks later. Saliva, mucosal tissues and bone around implants and teeth were processed and analyzed by flow-cytometry, RT-qPCR, micro-CT and immunofluorescence staining. To quantify the impact of titanium ions on the immune response, bone marrow cells were cultured with various titanium concentrations.
Results: Similarly to human studies, the cumulative survival rate of 200 posterior implants was over 80%. Langerhans cells (LC) were absent in the peri-implant epithelium. This was due to an alteration in epithelial expression of TGF-β1/ALK5 as well as TGF-β1/ALK3 signaling, which are known to instruct LCs differentiation. Interestingly, titanium ions had the capacity to dysregulate the development of LC-like cells in vitro implying on corrosion as etiology. The peri-implant mucosa contained large proportions of leukocyte and neutrophils with no evidence of an acute inflammation. Bone loss was measured around implants 10 weeks after implantation. In line with this observation, higher RANKL\OPG and IL17\FOXP3 ratios were found in the tissue around implants, together with elevated INF-α expression. Interestingly, the contra-lateral teeth of implanted mice displayed bone loss compared to teeth in non-implanted mice. These findings correlate with noted bacterial dysbiosis following implant insertion with the uprising of perio-pathogenic bacterial families in the implanted mice.
Conclusions: These findings suggest that titanium dental implants have the capacity to impair the development of oral LCs and subsequently to dysregulate local immunity. This new inflammatory milieu eventually leads to a microbial dysbiosis, involving the accumulation of inflammophilic bacteria resulting with bone loss around implants and contra-lateral teeth.