Effect of Metallic Particles on the Progression of Peri-Implantitis

N/ANot Yet RecruitingNCT07792499

University of Barcelona50 enrolled

Overview

This observational cross-sectional study aims to investigate the presence and characteristics of metallic micro- and nanoparticles in peri-implant tissues and their potential association with peri-implantitis progression, the local microbiota, and the host inflammatory response. The study will include 50 participants divided into two groups: individuals requiring dental implant placement, from whom healthy gingival tissue will be collected as an active control, and patients diagnosed with peri-implantitis, from whom granulation tissue and submucosal biofilm samples will be obtained. Tissue samples will be analysed to determine the concentration, size, morphology, and intracellular localisation of metallic particles, as well as macrophage polarisation. Microbiological analyses will characterise the peri-implant microbiota. Associations between metallic particle burden, microbiological composition, inflammatory response, and clinical and radiographic indicators of peri-implant disease severity and progression will also be explored.

This observational cross-sectional study will include 50 participants, with one study site per participant, divided equally into two groups. The active control group will include patients requiring the placement of at least one dental implant. A healthy gingival tissue sample will be collected immediately before implant placement, provided that the width of keratinised mucosa at the sampling site is at least 3 mm. The peri-implantitis group will include patients diagnosed according to the 2017 World Workshop case definition. Granulation tissue and a submucosal biofilm sample will be collected from the selected affected implant. Participants will not be assigned to any exposure or therapeutic intervention for research purposes. Tissue samples from both groups will be divided into subsamples and analysed using complementary laboratory techniques. Inductively coupled plasma triple quadrupole mass spectrometry will be used to quantify titanium, aluminium, vanadium, molybdenum, and chromium. Scanning and transmission electron microscopy will be used to characterise the size, morphology, distribution, and intracellular localisation of metallic particles. Histopathological and immunohistochemical analyses will evaluate tissue characteristics and macrophage polarisation. In the peri-implantitis group, 16S ribosomal RNA gene sequencing of submucosal biofilm samples will be performed to characterise the microbial community. A biofilm sample will not be collected from the active control group because these participants do not yet have an established peri-implantitis environment at the sampling site. Clinical, radiographic, implant-related, prosthetic, and participant-related variables will also be recorded. The study will compare the metallic particle burden and tissue characteristics between healthy gingival and peri-implantitis tissues. It will also explore associations between metallic particle burden, microbial composition, macrophage polarisation, and clinical and radiographic indicators of peri-implant disease severity and progression.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: To be considered eligible for participation in this study, patients must fulfil all the following criteria: 1. Written informed consent duly completed and signed for participation in the study and the use of biological samples. 2. Male or female patients aged 18 years or older. 3. Patients treated at the Master's Degree in Oral Surgery and Implantology or the Master's Degree in Periodontology and Peri-Implantology at the University of Barcelona. 4. Patients in full possession of their mental faculties and capable of understanding and providing written informed consent prior to enrolment in the study. 5. Willingness to comply with all study procedures required by the protocol. In addition, participants must meet the criteria for one of the following study groups: * Peri-implantitis Group: 1. Diagnosis of peri-implantitis according to the diagnostic criteria established at the 2017 World Workshop on the Classification of Periodontal and Peri- Implant Diseases and Conditions. 2. Candidate for surgical or non-surgical peri-implantitis treatment involving the collection of peri-implant granulation tissue and/or biofilm samples. * Control Group: 1. Candidate for implant therapy, with the placement of at least one dental implant included in the treatment plan. 2. Candidate for implant placement using a static computer-guided surgical approach. 3. Availability of soft tissue from the implant recipient site for sample collection (≥ 3 mm). Exclusion Criteria: To be considered eligible for participation in this study, patients must not fulfil any of the following criteria: 1. Patients who, in the investigator's judgement, are not suitable candidates for participation in the study based on their medical history, physical examination findings, concomitant medications, or concurrent systemic conditions: 1. Presence of uncontrolled periodontal disease, defined as probing depths ≥5 mm with concomitant bleeding on probing or probing depths ≥6 mm. 2. Immunocompromised patients. 3. History of radiotherapy or chemotherapy. 4. Presence of uncontrolled systemic diseases. 5. Presence of systemic conditions known to affect bone metabolism. 6. Current treatment with medications known to alter bone metabolism. 7. History of oral cancer. 8. Use of systemic antibiotics within the previous 6 months. 2. Current smokers consuming ≥20 cigarettes per day. 3. History of drug or alcohol abuse. For the purposes of this study, alcohol abuse is defined as the habitual consumption of more than four units of alcohol per day (one unit being approximately equivalent to 125 mL of wine, 200 mL of beer, or 25 mL of spirits). 4. Participation in any other clinical study within the 4 weeks preceding enrolment. 5. Surgical or non-surgical peri-implantitis treatment at the selected implant site within the 12 months preceding enrolment. 6. Pregnant or breastfeeding women.

Outcomes

Primary Outcomes

Concentration of metallic elements (Ti, Al, V, Mo and Cr) in tissue samples (ppb).

The concentrations of titanium (Ti), aluminium (Al), vanadium (V), molybdenum (Mo), and chromium (Cr) will be quantified separately in healthy gingival tissue and peri-implant granulation tissue using inductively coupled plasma triple quadrupole mass spectrometry (ICP-TQ-MS). The concentration of each metallic element will be reported in parts per billion (ppb) and compared between the active control and peri-implantitis groups. Unit of Measure: Parts per billion (ppb).

Time frame: Day 1

Secondary Outcomes

Microbial species richness and evenness within each sample (alpha diversity).

Alpha diversity of the submucosal microbiome will be assessed in biofilm samples collected from the peri-implant site with the greatest probing depth in participants with peri-implantitis. Bacterial DNA will be extracted and the microbiome characterised by 16S ribosomal RNA gene sequencing. Alpha diversity will describe microbial richness, defined as the number of microbial taxa detected within each sample, and evenness, defined as how uniformly their relative abundances are distributed. Results will be reported as alpha-diversity index values.

Time frame: Day 1

Microbial composition between samples from different clinical conditions (beta diversity).

Beta diversity of the submucosal microbiome will be assessed in biofilm samples collected from participants with peri-implantitis. Bacterial DNA will be extracted and the microbiome characterised by 16S ribosomal RNA gene sequencing. Beta diversity will quantify the degree of similarity or dissimilarity in the identity and relative abundance of microbial taxa between samples. These comparisons will be used to evaluate whether microbial community composition varies according to metallic particle concentration and the clinical characteristics of the sampled peri-implant sites. Results will be reported as beta-diversity distance values.

Time frame: Day 1

Percentage of TiO₂ Nanoparticles in Each Morphological Category

Titanium dioxide (TiO₂) nanoparticles will be evaluated in healthy gingival tissue from the active control group and peri-implant granulation tissue from the peri-implantitis group. High-resolution transmission electron microscopy (TEM) will be used to visualise the particles, and energy-dispersive X-ray spectroscopy (EDS/EDX) will confirm their elemental composition. Nanoparticles will be classified according to their observed shape and structural features. The percentage of identified TiO₂ nanoparticles in each morphological category will be reported for each sample. Unit of measure: %.

Time frame: Day 1

Mean Diameter of TiO₂ Nanoparticles

Titanium dioxide (TiO₂) nanoparticles will be evaluated in healthy gingival tissue from the active control group and peri-implant granulation tissue from the peri-implantitis group. High-resolution transmission electron microscopy (TEM) will be used to visualise the particles, and energy-dispersive X-ray spectroscopy (EDS/EDX) will confirm their elemental composition. Particle diameters will be measured using ImageJ image-analysis software, and the mean diameter of the identified TiO₂ nanoparticles in each sample will be reported in nanometres (Unit of Measure: nm).

Time frame: Day 1

Intracellular distribution of TiO₂ nanoparticles.

The intracellular presence and localisation of titanium dioxide (TiO₂) nanoparticles will be evaluated in cells isolated from healthy gingival tissue and peri-implant granulation tissue. Ultrathin tissue sections will be examined using high-resolution transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDS/EDX) will be used to confirm the elemental composition of the identified particles. The analysis will describe whether TiO₂ nanoparticles are located within cells and their distribution and interaction with intracellular structures.

Time frame: Day 1

Rate of peri-implant bone loss progression (mm/year)

In participants with peri-implantitis, peri-implant bone loss will be measured radiographically in millimetres at the time of biological sample collection. The estimated average annual rate of bone loss will be calculated by dividing the radiographic bone loss by the time elapsed, in years, from implant placement to sample collection. Higher values indicate a faster estimated rate of peri-implant bone loss. Results will be reported in millimetres per year (mm/year).

Time frame: Day 1

Macrophage polarisation (M1 versus M2 phenotype)

Macrophage polarisation will be assessed in healthy gingival tissue from the active control group and peri-implant granulation tissue from the peri-implantitis group. Paraffin-embedded tissue sections will undergo immunohistochemical analysis using established markers for pro-inflammatory M1 and anti-inflammatory and tissue-repair-associated M2 macrophage phenotypes. The relative distribution of both macrophage populations will be quantified and reported as the M1/M2 ratio. A higher ratio indicates a relative predominance of the pro-inflammatory M1 phenotype.

Time frame: Day 1

Number of TiO₂ Nanoparticles per Tissue Sample

Titanium dioxide (TiO₂) nanoparticles will be evaluated in healthy gingival tissue from the active control group and peri-implant granulation tissue from the peri-implantitis group. High-resolution transmission electron microscopy (TEM) will be used to visualise the particles, and energy-dispersive X-ray spectroscopy (EDS/EDX) will confirm their elemental composition. The number of identified TiO₂ nanoparticles in each tissue sample will be quantified using ImageJ image-analysis software and reported as the number of nanoparticles per sample.

Time frame: Day 1

Effect of Metallic Particles on the Progression of Peri-Implantitis

Overview

Conditions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts