Rodent peri-implantitis models: a systematic review and meta-analysis of morphological changes

Abstract

Purpose: Rodent models have emerged as an alternative to established larger animal models for peri-implantitis research. However, the construct validity of rodent models is controversial due to a lack of consensus regarding their histological, morphological, and biochemical characteristics. This systematic review sought to validate rodent models by characterizing their morphological changes, particularly marginal bone loss (MBL), a hallmark of peri-implantitis.

Methods: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed electronically using MEDLINE (PubMed), and Embase, identifying pre-clinical studies reporting MBL after experimental peri-implantitis induction in rodents. Each study's risk of bias was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool. A meta-analysis was performed for the difference in MBL, comparing healthy implants to those with experimental peri-implantitis.

Results: Of the 1,014 unique records retrieved, 23 studies that met the eligibility criteria were included. Peri-implantitis was induced using 4 methods: ligatures, lipopolysaccharide, microbial infection, and titanium particles. Studies presented high to unclear risks of bias. During the osseointegration phase, 11.6% and 6.4%-11.3% of implants inserted in mice and rats, respectively, had failed to osseointegrate. Twelve studies were included in the meta-analysis of the linear MBL measured using micro-computed tomography. Following experimental peri-implantitis, the MBL was estimated to be 0.25 mm (95% confidence interval [CI], 0.14-0.36 mm) in mice and 0.26 mm (95% CI, 0.19-0.34 mm) in rats. The resulting peri-implant MBL was circumferential, consisting of supra- and infrabony components.

Conclusions: Experimental peri-implantitis in rodent models results in circumferential MBL, with morphology consistent with the clinical presentation of peri-implantitis. While rodent models are promising, there is still a need to further characterize their healing potentials, standardize experiment protocols, and improve the reporting of results and methodology.

Trial registration: PROSPERO Identifier: CRD42020209776.

Keywords: Dental implants; Peri-implantitis; Rodentia; Systematic review.

Figure 1. PRISMA flow chart illustrating the selection process of the included studies.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Figure 2. Forest plot of micro-CT analysis for linear MBL.

CT: computed tomography, MBL: marginal bone loss, SD: standard deviation, CI: confidence interval.

Figure 3. Bubble plot depicting the effects of species (mice and rats) and the protocol used for inducing peri-implantitis on the MBL.

MBL: marginal bone loss.

Figure 4. ROB evaluated using the SYRCLE RoB tool, reported as the percentage per criterion.

RoB: Risk of Bias, SYRCLE: Systematic Review Center for Laboratory animal Experimentation.