Dental Implant Material Related Changes in Molecular Signatures in Peri-Implantitis - A Systematic Review and Integrative Analysis of Omics In-Vitro Studies

Objective: Titanium particles have been shown in in-vitro studies to lead to the activation of specific pathways, this work aims to systematically review in-vivo studies examining peri-implant and periodontal tissues at the transcriptome, proteome, epigenome and genome level to reveal implant material-related processes favoring peri-implantitis development investigated in animal and human trials.Methods: Inquiring three literature databases (Medline, Embase, Cochrane) a systematic search based on a priori defined PICOs was conducted: '-omics' studies comparing molecular signatures in healthy and infected peri-implant sites and/or healthy and periodontitis-affected teeth in animals/humans. After risk of bias assessments, lists of differentially expressed genes and results of functional enrichment analyses were compiled whenever possible. Results: Out of 2187 screened articles 9 publications were deemed eligible. Both healthy and inflamed peri-implant tissues showed distinct gene expression patterns compared to healthy/diseased periodontal tissues in animal (n = 4) or human studies (n = 5), with immune response, bone metabolism and oxidative stress being affected the most. Due to the lack of available reanalyzable data and inconsistency in methodology of the eligible studies, integrative analyses on differential gene expression were not applicable Conclusion: The differences of transcriptomic signatures in between peri-implant lesions compared to periodontal tissue might be related to titanium particles arising from dental implants and are in line with the in-vitro data recently published by our group. Nevertheless, limitations emerge from small sample sizes of included studies and insufficient publication of re-analyzable data.