A Murine Model of Lipopolysaccharide-Induced Peri-Implant Mucositis and Peri-Implantitis
Dental implants are a widely used treatment option for tooth replacement. However, they are susceptible to inflammatory diseases such as peri-implant mucositis and peri-implantitis, which are highly prevalent and may lead to implant loss. Unfortunately, the understanding of the pathogenesis of peri-implant mucositis and peri-implantitis is fragmented and incomplete. Therefore, the availability of a reproducible animal model to study these inflammatory diseases would facilitate the dissection of their pathogenic mechanisms. The objective of this study is to propose a murine model of experimental peri-implant mucositis and peri-implantitis. Screw-shaped titanium implants were placed in the upper healed edentulous alveolar ridges of C57BL/6J mice 8 weeks after tooth extraction. Following 4 weeks of osseointegration, Porphyromonas gingivalis-lipolysaccharide (LPS) injections were delivered to the peri-implant soft tissues for 6 weeks. No-injections and vehicle injections were utilized as controls. Peri-implant mucositis and peri-implantitis were assessed clinically, radiographically (microcomputerized tomograph [CT]), and histologically following LPS-treatment. LPS-injections resulted in a significant increase in soft tissue edema around the head of the implants as compared to the control groups. Micro-CT analysis revealed significantly greater bone loss in the LPS-treated implants. Histological analysis of the specimens demonstrated that the LPS-group had increased soft tissue vascularity, which harbored a dense mixed inflammatory cell infiltrate, and the bone exhibited noticeable osteoclast activity. The induction of peri-implant mucositis and peri-implantitis in mice via localized delivery of bacterial LPS has been demonstrated. We anticipate that this model will contribute to the development of more effective preventive and therapeutic approaches for these 2 conditions.
(a) Schematic diagram depicting timing of the experimental design. (b) Representative clinical image of the implant fixtures utilized in the development of the peri-implant mucositis and peri-implantitis murine model.
(a) Representative clinical image of the mouse maxilla at 4 weeks after implant placement. (b) Representative clinical images of a mouse maxilla in the (b) noninjected, (c) vehicle-injected, and (d) LPS-injected groups at 6 weeks after initiation of implant treatment. (e) Graph represents surface area exposed by soft tissue of the noninjected, vehicle-injected, and LPS-injected groups 6 weeks after injections were initiated. Data are mean ± SEM. ***P < .0001 compared to control and +++P < .0001 compared to vehicle (n ≥ 5/group).
(a) Representative microcomputerized tomography images—sagittal and coronal planes—6 weeks after initiation of treatment (noninjected, vehicle-injected, and LPS-injected groups). (b) Graph represents bone levels as measured by the distance of the implant head to the alveolar bone crest on the palatal aspect of the fixtures. Data are mean ± SEM. *P < .05 compared to noninjected and +P < .05 compared to vehicle-injected (n ≥ 7/group).
(a) Representative images of toluidine blue stained sections 6 weeks after treatment (noninjected, vehicle-injected, and LPS-injected groups); magnification ×100. Notice different bone levels between the experimental and the control/vehicle groups. Black arrows represent osteoclasts. (b) Representative images of hematoxylin and eosin stained sections 6 weeks after treatment weeks after treatment (control, vehicle, and experimental groups), magnification ×100. Notice the presence of a dense mixed inflammatory cell infiltrate in the experimental group as compared to the control/vehicle groups.
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