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.
