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- The association between inflammation in peri implantitis and bio-tribocorrosion: systematic reviewPublication . Furlanetto, Marco; Soares, Clara; Macedo, José PauloA systematic review was conducted to evaluate the relationship between titanium metal particles and the development of periimplantitis, specifically: characterization of the inflammatory response regarding cytokine profile in the peri-implant sites, immune cells infiltration and transcription factors up-regulated. This work followed the PRISMA statement, and the literature search was performed, from January 2004 to January 2025, in 3 databases: PubMed, Web of Science and Wiley Library. The inclusion criteria involved articles published in english language, reporting in vivo human studies or in vitro with focus on bio-tribocorrosion of titanium particles around peri-implant soft tissues and their immunological and cellular implications. Quality assessment was based in the Joanna Briggs Institute Critical Appraisal Tools and CONSORT checklist. Of 127 potentially eligible studies, 27 were included: 20 in vitro and 7 in vivo. The median quality assessment score for in vitro studies was 8/14; for in vivo studies, five had no risk of bias and 2 had a moderate risk. There was an increase in the expression levels of IL1- β, TNF-α and IL-6 produced by macrophages, epithelial cells and fibroblasts. In osteoblasts, TNF-α stimulated bone resorption by modulating the RANK-L/OPG balance. There was a significant increase in IL-33 in peri-implant areas associated with higher concentrations of titanium particles and IL-8 production by gingival stromal cells and fibroblasts, regardless of LPS. VEGF was significantly detected in biopsies from patients with peri-implantitis and in peri-implant crevicular fluid, and CCR7 expression decreased in dendritic cells and macrophages. NLRP3, an inflammasome, was up-regulated in response to titanium particles by macrophages, epithelial and mesenchymal stromal cells, and increased levels of DNA methylation were observed in peri-implant tissue. Histological analyses detected mostly neutrophils, macrophages and plasma cells in the peri-implant tissue, and titanium particles were not associated with the presence of multinucleated giant cells. Bio-tribocorrosion of titanium particles stimulates a chronic inflammatory response, activation of the NRLP3 inflammasome and secretion of IL-1β, IL-6 and TNFα in the peri-implant tissue, leading to RANKL/OPG bone resorption. The cytokine IL-33, an alarmin, increased this cellular immune reaction, being constantly produced in response to implant-pillar micromovements. In addition, the production of IL-8 induced by titanium particles attracts neutrophils and monocytes to the site and also acts directly on osteoclasts, causing bone loss. The negative regulation of CCR7 may explain the altered leukocyte migration and the mixture of M1/M2 macrophage populations observed in the granular tissue, ultimately affecting the balance between a successful or failed implant. As far as epigenetic changes are concerned, titanium particles appear to induce DNA methylation, but more studies are needed. Titanium particles are detected in peri-implant tissue in the absence of multinucleated giant cells, suggesting that titanium-induced foreign body reaction is not one of the pathways for osteolysis in peri-implantitis. In the future, immune cell composition and cytokine secretion may help to develop strategies for therapeutic approaches to peri-implantitis, modulating the immune response and helping to prevent implant failure, specifically with the use of biomarkers.