Daniela Moreira Cunha, Amanda Paino Santana, Mariana Martins Guerreiro, Akhilanand Chaurasia, Anton Sculean, Rafael Scaf de Molon, Erica Dorigatti de Avila
<p>There is no doubt that peri-implantitis is an inflammatory condition affecting the tissues surrounding dental implants, driven by a complex interplay between microbial dysbiosis and the host immune response [<span>1</span>]. Subclinical interactions between the dysbiotic biofilm and the host immune system are initiated largely by components of anaerobic Gram-negative bacteria, most notably lipopolysaccharide (LPS), which predominates at diseased peri-implant sites. LPS engages toll-like receptor 4 (TLR4) on epithelial and immune cells, activating transcriptional pathways that upregulate proinflammatory mediators and establish a permissive environment for leukocyte recruitment [<span>2</span>]. Neutrophils, macrophages, and dendritic cells are rapidly mobilized and amplify tissue destruction through the release of cytokines and extracellular matrix-degrading enzymes. Among these innate immune cells, macrophages play a particularly central role in peri-implant disease pathogenesis, exhibiting a pronounced shift toward an M1-dominant phenotype [<span>3, 4</span>]. Interestingly, macrophage polarization has also been implicated as a key pathogenic mechanism across a broad spectrum of chronic inflammatory diseases, including cancer, diabetes, atherosclerosis, and periodontitis [<span>5, 6</span>] supporting the notion that peri-implantitis may share pathogenic pathways with, and potentially associate with, other local and systemic inflammatory conditions. M1-polarized macrophages produce RANKL, reactive oxygen species, and matrix metalloproteinases, thereby promoting osteoclastogenesis and accelerating bone resorption. Neutrophils further contribute through membrane-bound RANKL expression and heightened sensitivity to microbial cues. As disease progresses, adaptive immunity becomes similarly dysregulated, with helper T-cells (CD4<sup>+</sup> T)-cell subsets, including Th1, Th2, Th17 cells, and regulatory T cells (Tregs), sustaining chronic inflammation and driving interleukin (IL-)17-mediated neutrophil recruitment and osteoclast activation. Tregs, characterized by expression of transcription factor forkhead box p3 (FOXP3), cluster of differentiation (CD)25, and the IL-2 receptor, are markedly elevated in peri-implantitis lesions and are typically associated with the production of IL-10, tgf beta growth factor (TGF)-β1, and IL-35. While IL-10 and TGF-β1 function as baseline homeostatic anti-inflammatory mediators, IL-35 is induced under intense inflammatory pressure. The observed imbalance with elevated FOXP3 and IL-35 coupled with reduced TGF-β1 suggests a dysfunctional or unstable Treg phenotype unable to effectively restrain inflammation, thereby contributing to the progressive soft- and hard-tissue destruction characteristic of peri-implantitis [<span>7</span>].</p><p>In simple terms, a dysbiotic biofilm, an imbalanced and pathogenic microbial community adhered to the implant surface, acts as the primary trigger, initiating an inflammatory casc
{"title":"Reconceptualizing Peri-Implantitis: Dual-Factor Inflammation and Its Role in Advancing Biomaterial Coatings","authors":"Daniela Moreira Cunha, Amanda Paino Santana, Mariana Martins Guerreiro, Akhilanand Chaurasia, Anton Sculean, Rafael Scaf de Molon, Erica Dorigatti de Avila","doi":"10.1111/cid.70108","DOIUrl":"10.1111/cid.70108","url":null,"abstract":"<p>There is no doubt that peri-implantitis is an inflammatory condition affecting the tissues surrounding dental implants, driven by a complex interplay between microbial dysbiosis and the host immune response [<span>1</span>]. Subclinical interactions between the dysbiotic biofilm and the host immune system are initiated largely by components of anaerobic Gram-negative bacteria, most notably lipopolysaccharide (LPS), which predominates at diseased peri-implant sites. LPS engages toll-like receptor 4 (TLR4) on epithelial and immune cells, activating transcriptional pathways that upregulate proinflammatory mediators and establish a permissive environment for leukocyte recruitment [<span>2</span>]. Neutrophils, macrophages, and dendritic cells are rapidly mobilized and amplify tissue destruction through the release of cytokines and extracellular matrix-degrading enzymes. Among these innate immune cells, macrophages play a particularly central role in peri-implant disease pathogenesis, exhibiting a pronounced shift toward an M1-dominant phenotype [<span>3, 4</span>]. Interestingly, macrophage polarization has also been implicated as a key pathogenic mechanism across a broad spectrum of chronic inflammatory diseases, including cancer, diabetes, atherosclerosis, and periodontitis [<span>5, 6</span>] supporting the notion that peri-implantitis may share pathogenic pathways with, and potentially associate with, other local and systemic inflammatory conditions. M1-polarized macrophages produce RANKL, reactive oxygen species, and matrix metalloproteinases, thereby promoting osteoclastogenesis and accelerating bone resorption. Neutrophils further contribute through membrane-bound RANKL expression and heightened sensitivity to microbial cues. As disease progresses, adaptive immunity becomes similarly dysregulated, with helper T-cells (CD4<sup>+</sup> T)-cell subsets, including Th1, Th2, Th17 cells, and regulatory T cells (Tregs), sustaining chronic inflammation and driving interleukin (IL-)17-mediated neutrophil recruitment and osteoclast activation. Tregs, characterized by expression of transcription factor forkhead box p3 (FOXP3), cluster of differentiation (CD)25, and the IL-2 receptor, are markedly elevated in peri-implantitis lesions and are typically associated with the production of IL-10, tgf beta growth factor (TGF)-β1, and IL-35. While IL-10 and TGF-β1 function as baseline homeostatic anti-inflammatory mediators, IL-35 is induced under intense inflammatory pressure. The observed imbalance with elevated FOXP3 and IL-35 coupled with reduced TGF-β1 suggests a dysfunctional or unstable Treg phenotype unable to effectively restrain inflammation, thereby contributing to the progressive soft- and hard-tissue destruction characteristic of peri-implantitis [<span>7</span>].</p><p>In simple terms, a dysbiotic biofilm, an imbalanced and pathogenic microbial community adhered to the implant surface, acts as the primary trigger, initiating an inflammatory casc","PeriodicalId":50679,"journal":{"name":"Clinical Implant Dentistry and Related Research","volume":"28 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cid.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}