Titanium Particle Release Across Non-Surgical Peri-implantitis Therapies
Evaluation of the Effects of Peri-implantitis Treatment Approaches on Titanium Particle Release
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background and Rationale:
Peri-implantitis is a multifactorial inflammatory disease characterized by inflammation in the peri-implant soft tissues and progressive loss of supporting crestal bone. Non-surgical treatment protocols primarily aim to eliminate pathogenic bacterial biofilm and reduce local inflammation. However, mechanical forces and physical methods applied during these procedures can cause micro- and macro-level surface alterations on dental implants, leading to the release of metallic micro- and nanoparticles into the surrounding tissues. These released metal ions and particles can trigger foreign body reactions, macrophage polarization, and elevated cytokine expression, thereby exacerbating bone resorption independently of the biofilm. Although various non-surgical decontamination methods are clinically utilized, data evaluating their short- and medium-term metal release kinetics alongside clinical outcomes through prospective in vivo designs remain limited.
Objectives and Hypotheses:
The primary objective of this study is to prospectively compare the clinical efficacy of four different non-surgical decontamination methods and to quantitatively assess their impact on multi-element trace metal release (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) in peri-implant sulcular fluid (PISF) and granulation tissue. The study will test hypotheses regarding whether different treatment modalities create significant differences in clinical parameters (Probing Depth, Plaque Index, Bleeding on Probing, Gingival Index, Clinical Attachment Level) and metal ion load, while determining the most biocompatible and minimally invasive protocol.
Study Design and Patient Population:
This study is designed as a prospective, randomized, controlled, single-blind, in vivo clinical and laboratory trial. A total of 70 implants will be evaluated: 56 peri-implantitis implants and 14 healthy control implants. Peri-implantitis cases will be randomly allocated using computer-generated block randomization via the sequentially numbered opaque sealed envelope (SNOSE) method into four parallel treatment groups (14 implants per group):
Group 1 (Titanium Curette): Mechanical debridement using titanium curettes (10-15 strokes per surface horizontally and apico-coronally).
Group 2 (Plastic Curette): Mechanical debridement using implant-compatible plastic curettes adhering to the same stroke and directional principles.
Group 3 (Diode Laser): Diode laser application (940 nm, 1 W average power, non-contact mode, 300 µm fiber tip for 60 seconds).
Group 4 (EMS Air-Flow + PEEK): Guided Biofilm Therapy (GBT) protocol utilizing submarginal erythritol powder via PerioFlow nozzle, followed by a PEEK instrument (Piezon PI) to remove remaining calcified deposits.
Group 5 (Healthy Control): Individuals with peri-implant health receiving no treatment intervention, undergoing clinical monitoring and PISF collection only.
Procedures and Assessments:
Clinical Parameters: Probing Depth (PD), Bleeding on Probing (BoP), Plaque Index (PI), Gingival Index (GI), and Clinical Attachment Level (CAL) will be recorded at baseline (T0) and at 6 weeks (T2) by a blinded and calibrated investigator. PISF Sampling: Peri-implant sulcular fluid samples will be collected using sterile paper strips (Periopaper) at baseline (T0), 24 hours post-treatment (T1), and 6 weeks post-treatment (T2). Fluid volume will be measured via Periotron and stored at -80°C.
Granulation Tissue Sampling: Inflammatory granulation tissue samples will be collected during debridement (or via gentle sulcular sampling for laser and air-flow groups, strictly avoiding contact with the titanium surface) and placed in sterile eppendorf tubes.
ICP-MS Analysis: Biological samples will undergo microwave-assisted acid digestion and quantitative elemental analysis (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) at an accredited laboratory. Baseline metal loads of materials (such as erythritol powder and blank Periopaper strips) will be accounted for and subtracted.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Özlem SARAÇ ATAGÜN, DDS, Assoc. Prof.
- Phone Number: +905055096482
- Email: ozlemsarac2806@hotmail.com
Study Contact Backup
- Name: İrem Sezen, DDS, PhD Candidate
- Phone Number: +905426982624
- Email: iremszn@gmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Being systemically healthy and older than 18 years of age.
- Having implants diagnosed with peri-implantitis according to the 2017 World Workshop criteria (probing depth ≥ 5 mm, bleeding on probing positive, radiographic bone loss > 2 mm).
- Dental implants being in function in the oral cavity for at least 1 year.
Exclusion Criteria:
- Having received systemic antibiotic therapy within the past 3 months.
- Having previously received peri-implantitis treatment at the relevant implant site.
- Being pregnant or lactating.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Arm 1: Titanium Curette Group
Mechanical debridement performed using specialized medical-grade titanium curettes.
The treatment protocol involves applying 10-15 systematic strokes per implant surface in both horizontal and apico-coronal directions to thoroughly decontaminate the infected implant threads and remove subgingival biofilm and calculus.
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This arm evaluates standard mechanical debridement using medical-grade titanium curettes, applied as 10-15 systematic strokes per implant surface horizontally and apico-coronally.
Unlike conventional studies that focus solely on clinical indices, this protocol uniquely combines mechanical cleaning with quantitative Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis to measure multi-element trace metal release (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) in both peri-implant sulcular fluid (PISF) and inflammatory granulation tissue, determining the specific particulate load generated by metallic curettage.
Other Names:
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Experimental: Arm 2: Plastic Curette Group
Mechanical debridement performed using implant-compatible, flexible plastic curettes.
The procedure strictly adheres to the same standardized stroke count and directional mechanics (10-15 strokes per surface horizontally and apico-coronally) to minimize aggressive surface scratching while eliminating bacterial plaque.
|
This arm utilizes implant-compatible, flexible plastic curettes adhering to identical stroke parameters (10-15 strokes per surface horizontally and apico-coronally).
Its unique methodological value lies in comparing polymer-based mechanical instrumentation against metallic counterparts, specifically quantifying whether non-metallic mechanical debridement mitigates multi-element trace metal release (analyzed via ICP-MS across 11 elemental parameters in PISF and granulation tissue) while maintaining therapeutic clinical efficacy in peri-implantitis management.
Other Names:
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Experimental: Arm 3: Diode Laser Group
Laser-assisted surface decontamination utilizing a diode laser system operating at a wavelength of 940 nm.
The protocol is administered in a non-contact mode with an average power of 1 W, utilizing a 300 µm fiber tip applied for 60 seconds per implant surface to achieve bactericidal and decontamination effects.
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This arm implements a laser-assisted decontamination protocol using a 940 nm diode laser operated in non-contact mode at an average power of 1 W with a 300 µm fiber tip applied for 60 seconds per surface.
This intervention investigates the thermal and bactericidal efficacy of optical decontamination, uniquely pairing it with high-precision ICP-MS trace metal quantification (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) from PISF and granulation tissue samples to evaluate whether photon-based decontamination induces surface alterations or ion shedding compared to mechanical modalities.
Other Names:
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Experimental: Arm 4: EMS Air-Flow + PEEK Group
A two-step Guided Biofilm Therapy (GBT) approach.
First, submarginal air-polishing is performed using erythritol powder delivered via a specialized PerioFlow nozzle to remove soft biofilm.
Second, residual hard deposits are carefully cleared using a medical-grade PEEK (Polyetheretherketone) instrument (Piezon PI) designed to prevent titanium surface scarring.
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This arm employs a two-step Guided Biofilm Therapy (GBT) protocol combining submarginal air-polishing with erythritol powder via a PerioFlow nozzle followed by a medical-grade PEEK (Piezon PI) instrument for hard deposit removal.
This advanced combination protocol is uniquely designed to eliminate biofilm without scarring the titanium surface, its safety and efficacy rigorously validated through quantitative multi-element ICP-MS analysis of 11 trace metals in PISF and granulation tissue samples collected at baseline, 24 hours, and 6 weeks.
Other Names:
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Other: Arm 5: Healthy Control Group
Individuals presenting with healthy peri-implant tissues who receive no therapeutic or surgical decontamination intervention.
This cohort serves as a non-intervention control group to establish baseline comparative values for clinical metrics, peri-implant sulcular fluid (PISF) volume, and multi-element trace metal concentrations.
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This non-intervention control cohort comprises individuals with clinically healthy dental implants who receive no surgical or therapeutic decontamination.
It serves as a vital comparative baseline for the study, allowing researchers to evaluate physiological baseline levels of multi-element trace metal concentrations (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) in PISF and tissue samples relative to diseased, treated implant sites without confounding therapeutic variables.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Multi-Element Trace Metal Concentrations (Titanium Ion Release) in Peri-Implant Sulcular Fluid (PISF)
Time Frame: Baseline (T0), 24 hours post-treatment (T1), and 6 weeks post-treatment (T2)
|
Quantitative analysis of multi-element trace metal concentrations-specifically Titanium (Ti) along with Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, and Pb-released into the peri-implant sulcular fluid (PISF).
PISF samples will be collected using sterile Periopaper strips, quantified via Periotron, stored at -80°C, and analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) following microwave-assisted acid digestion, subtracting baseline material blanks.
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Baseline (T0), 24 hours post-treatment (T1), and 6 weeks post-treatment (T2)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in Probing Depth (PD)
Time Frame: Baseline (T0) and 6 weeks post-treatment (T2)
|
Assessment of peri-implant pocket depth reduction measured in millimeters using a standardized periodontal probe from the mucosal margin to the base of the peri-implant pocket.
All measurements will be recorded by a blinded and calibrated investigator.
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Baseline (T0) and 6 weeks post-treatment (T2)
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Change in Bleeding on Probing (BoP)
Time Frame: Baseline (T0) and 6 weeks post-treatment (T2)
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Evaluation of mucosal inflammation around the dental implants, recorded dichotomously as the presence or absence of bleeding within 30 seconds following gentle probing of the peri-implant sulcus.
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Baseline (T0) and 6 weeks post-treatment (T2)
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Change in Plaque Index (PI)
Time Frame: Baseline (T0) and 6 weeks post-treatment (T2)
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Quantification of microbial plaque accumulation and oral hygiene status surrounding the dental implant sites, evaluated using standardized clinical scoring criteria.
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Baseline (T0) and 6 weeks post-treatment (T2)
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Change in Gingival Index (GI)
Time Frame: Baseline (T0) and 6 weeks post-treatment (T2)
|
Assessment of the severity of peri-implant mucosal inflammation based on visual characteristics and tissue response to mild probing around the implant perimeter.
|
Baseline (T0) and 6 weeks post-treatment (T2)
|
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Change in Clinical Attachment Level (CAL)
Time Frame: Baseline (T0) and 6 weeks post-treatment (T2)
|
Quantification of the distance from a fixed anatomical or prosthetic reference point (such as the implant shoulder or crown margin) to the base of the pocket, serving as an indicator of supporting tissue status.
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Baseline (T0) and 6 weeks post-treatment (T2)
|
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Change in Multi-Element Trace Metal Concentrations in Inflammatory Granulation Tissue
Time Frame: Only at baseline (T0) during debridement
|
Quantitative elemental analysis of multi-element trace metal levels (Ti, Al, V, Co, Cr, Cu, Zr, Fe, Ni, As, Pb) in inflammatory granulation tissue samples collected during debridement (or via gentle sulcular sampling for non-contact groups) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) following microwave-assisted acid digestion.
|
Only at baseline (T0) during debridement
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Periodontal Diseases
- Mouth Diseases
- Stomatognathic Diseases
- Peri-Implantitis
- Health Services Administration
- Health Care Quality, Access, and Evaluation
- Therapeutics
- Health Care Evaluation Mechanisms
- Quality of Health Care
- Outcome Assessment, Health Care
- Outcome and Process Assessment, Health Care
- Epidemiologic Study Characteristics
- Watchful Waiting
- Clinical Protocols
Other Study ID Numbers
- OSATAGUN6
- Secondary ID 2026/290 (Other Identifier: University of Health Sciences, Gulhane NonPharmaceutical and Non-Medical Device Interventional Research EthicsCommittee)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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