Investigation of Macrophage Polarization in Peri-implant Health and Peri-implantitis

Peri-implantitis is a chronic inflammatory disease characterized by plaque-associated inflammation of the peri-implant mucosa and progressive loss of supporting bone around dental implants, which may ultimately lead to implant failure if left untreated.

It has been demonstrated that cellular and molecular responses of the host immune defense system play a critical role in the pathogenesis of peri-implantitis. Macrophages are key cells in the host immune response and are generally classified into two phenotypes: pro-inflammatory (M1) and anti-inflammatory (M2). While M1 macrophages are actively involved in the early defense response, a shift toward the M2 phenotype is required for the resolution of inflammation and tissue repair.

Smoking has been shown to adversely affect macrophage polarization and function, thereby exacerbating inflammatory responses. Therefore, in the present study, levels of soluable CD163 (sCD163), B cell activating factor (BAFF), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a proliferation-inducing ligand (APRIL), interferon-gamma (IFN-γ), interleukin-10 (IL-10), interleukin-34 (IL-34), interleukin-35 (IL-35), and arginase activity (ornithine levels) will be evaluated in peri-implant health and peri-implantitis patients with varying disease severity and different smoking statuses. In addition, a comprehensive proteomic analysis will be performed to investigate the relationships among peri-implantitis severity, smoking, and macrophage polarization-related molecules. Baseline periodontal and peri-implant parameters will be recorded for all participants. In the peri-implant health group, tissue samples will be collected during exposure surgery performed for submerged implants, after which participants will be enrolled in supportive peri-implant care. Participants diagnosed with peri-implantitis will receive non-surgical therapy, during which tissue samples will be collected. Periodontal and peri-implant parameters will be reassessed for all participants at baseline, and at 6 and 12 weeks. Healthy peri-implant samples will be collected from submerged implants during exposure surgery. Peri-implantitis samples (probable pocket depth ≥ 6 mm with bleeding on probing) will be obtained during non-surgical therapy using a single stroke along the pocket wall.

Study Overview

• Status: Recruiting
• Conditions: Peri-implantitis

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Recruiting
    • Biruni University
    • Contact: Burcu Karaduman; Phone Number: +905323763366; Email: bkaraduman@biruni.edu.tr
    • Sub-Investigator: Ayse Kaban

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals who applied to Biruni University Faculty of Dentistry for treatment or oral examination will be included in this study.

Description

Inclusion Criteria:

• Individuals who is suitable for the peri-implantitis diagnosis according to the classifications of periodontal and peri-implant diseases and conditions established in 2017.
• Individuals with at least one bone-level dental implant and scheduled to undergo exposure surgery.

Exclusion Criteria:

• prior peri-implantitis surgery
• being diagnosed with autoimmune disease, genetic disorders, bone metabolism disorders, poorly controlled systemic diseases (such as diabetes or hypertension)
• pregnancy or lactation
• having a history of oral malignancy, chemotherapy or radiotherapy
• use of anti-inflammatory drugs within 2 weeks, antibiotics within 3 months,
• need for prophylactic antibiotics
• contraindications for dental/surgical procedures.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Peri-implant health - smokers; Individuals with at least one bone-level dental implant, who are current smokers, and are scheduled to undergo exposure surgery.
Peri-implant health - non-smokers; Individuals with at least one bone-level dental implant, who are non-smokers, and are scheduled to undergo exposure surgery.
Peri-implantitis - non-smokers; Individuals with peri-implantitis (non-smokers) were defined as subjects who were non-smokers and presented with bleeding and/or suppuration on gentle probing, an increased probing depth compared to previous examinations, and radiographic evidence of bone loss beyond crestal bone level changes resulting from initial bone remodelling. In cases where previous examination data were not available, peri-implantitis was diagnosed based on the presence of bleeding and/or suppuration on gentle probing, probing depths of ≥6 mm, and radiographic bone levels ≥3 mm apical to the most coronal portion of the intraosseous part of the implant.
Peri-implantitis - smokers; Individuals with peri-implantitis (smokers) were defined as subjects who were current smokers and presented with bleeding and/or suppuration on gentle probing, an increased probing depth compared to previous examinations, and radiographic evidence of bone loss beyond crestal bone level changes resulting from initial bone remodelling. In cases where previous examination data were not available, peri-implantitis was diagnosed based on the presence of bleeding and/or suppuration on gentle probing, probing depths of ≥6 mm, and radiographic bone levels ≥3 mm apical to the most coronal portion of the intraosseous part of the implant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of soluable CD163 (sCD163) levels	sCD163 levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of a proliferation-inducing ligand (APRIL) levels	APRIL levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of B-cell activating factor (BAFF) levels	BAFF levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) levels	TWEAK levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluotion of interleukin-10 (IL-10) levels	IL-10 levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of interleukin-34 (IL-34) Levels	IL-34 levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of interleukin-35 (IL-35) levels	IL-35 levels in tissue samples collected from the participants will be evaluated using Bio-Plex multiplex kits. The results of the biochemical analyses will be reported as pg/ng.	Baseline
Evaluation of arginase activity	Arginase activity in tissue samples collected from the participants will be evaluated using Chinard's method by determined ornithine levels. The results of the biochemical analyses will be reported as pg/ng.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probable pocket depth (PPD)	Probable pocket depth wiil be measured using a periodontal probe	Baseline and 6th week.
Bleeding on probing (BoP)	The presence of visible bleeding following periodontal probing will be assessed by visual inspection (+/-). The total bleeding score will be expressed as a percentage.	Baseline and 6th week.
Plaque index	The presence of visible plaque will be evaluated with a periodontal probe (+/-). The total plaque score will be expressed as a percentage.	Baseline and 6th week.

Collaborators and Investigators

• Sponsor: Biruni University
• Collaborators: University of Turku; The Scientific and Technological Research Council of Turkey
• Investigators: Study Chair: Burcu Karaduman, PhD, Biruni University; Study Chair: Ulvi K Gursoy, PhD, University of Turku; Study Chair: Mustafa Yilmaz, PhD, Istanbul University; Principal Investigator: Ayse Kaban, Biruni University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: April 29, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: smoking; peri-implantitis; macrophage
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Behavior; Peri-Implantitis; Smoking
• Other Study ID Numbers: 2024-BIAEK/16-60

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No