Effect of Metallic Particles on the Progression of Peri-Implantitis
Effect of Metallic Micro- and Nanoparticles on the Progression of Peri-Implantitis and Their Interaction With the Microbiota
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.
Visão geral do estudo
Status
Condições
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Contactos e Locais
Contato de estudo
- Nome: Octavi Camps Font, DDS MS PhD
- Número de telefone: +34 934 024 269
- E-mail: ocamps@ub.edu
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Método de amostragem
População do estudo
Descrição
Inclusion Criteria: To be considered eligible for participation in this study, patients must fulfil all the following criteria:
- Written informed consent duly completed and signed for participation in the study and the use of biological samples.
- Male or female patients aged 18 years or older.
- 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.
- Patients in full possession of their mental faculties and capable of understanding and providing written informed consent prior to enrolment in the study.
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:
- 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.
- Candidate for surgical or non-surgical peri-implantitis treatment involving the collection of peri-implant granulation tissue and/or biofilm samples.
Control Group:
- Candidate for implant therapy, with the placement of at least one dental implant included in the treatment plan.
- Candidate for implant placement using a static computer-guided surgical approach.
- 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:
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:
Presence of uncontrolled periodontal disease, defined as probing depths
≥5 mm with concomitant bleeding on probing or probing depths ≥6 mm.
- Immunocompromised patients.
- History of radiotherapy or chemotherapy.
- Presence of uncontrolled systemic diseases.
- Presence of systemic conditions known to affect bone metabolism.
- Current treatment with medications known to alter bone metabolism.
- History of oral cancer.
- Use of systemic antibiotics within the previous 6 months.
- Current smokers consuming ≥20 cigarettes per day.
- 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).
- Participation in any other clinical study within the 4 weeks preceding enrolment.
- Surgical or non-surgical peri-implantitis treatment at the selected implant site within the 12 months preceding enrolment.
- Pregnant or breastfeeding women.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
Coortes e Intervenções
Grupo / Coorte |
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Peri-implantitis
Inclusion Criteria Adult patients (≥18 years old) diagnosed with peri-implantitis according to the definition established by the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions (Berglundh et al., 2018).
Implants presenting bleeding on probing and/or suppuration, increased probing depth, and progressive bone loss compared with previous records.
When previous records are unavailable, implants will be included if they present bleeding and/or suppuration on gentle probing, probing depth ≥ 6 mm, and a bone level ≥ 3 mm apical to the most coronal portion of the implant's rough surface.
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Control: prior to implant placement
To be considered eligible for participation in this study, patients must fulfil all the following criteria:
In addition, participants must meet the criteria for being part of the control group:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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Concentration of metallic elements (Ti, Al, V, Mo and Cr) in tissue samples (ppb).
Prazo: Day 1
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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).
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Day 1
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Microbial species richness and evenness within each sample (alpha diversity).
Prazo: Day 1
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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.
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Day 1
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Microbial composition between samples from different clinical conditions (beta diversity).
Prazo: Day 1
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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.
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Day 1
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Percentage of TiO₂ Nanoparticles in Each Morphological Category
Prazo: Day 1
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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: %.
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Day 1
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Mean Diameter of TiO₂ Nanoparticles
Prazo: Day 1
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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).
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Day 1
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Intracellular distribution of TiO₂ nanoparticles.
Prazo: Day 1
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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.
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Day 1
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Rate of peri-implant bone loss progression (mm/year)
Prazo: Day 1
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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).
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Day 1
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Macrophage polarisation (M1 versus M2 phenotype)
Prazo: Day 1
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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.
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Day 1
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Number of TiO₂ Nanoparticles per Tissue Sample
Prazo: Day 1
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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.
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Day 1
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Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
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Presence of Plaque at the Selected Implant
Prazo: Day 1
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Plaque will be clinically assessed at six sites around the selected implant in participants with peri-implantitis.
At each peri-implant site, plaque will be recorded dichotomously as present or absent.
Results will be reported as the presence or absence of plaque at each of the six assessed sites.
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Day 1
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Probing Depth (PPD, mm)
Prazo: Day 1
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Depth of peri-implant sulcus measured at six sites per implant using standardized probing force (20-25 g).
Unit of Measure: millimeters (mm)
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Day 1
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Bleeding and/or Suppuration on Probing (BoP/SoP)
Prazo: Day 1
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Presence of bleeding and/or suppuration elicited within 30 seconds after gentle probing at six sites per implant using a standardized periodontal probe.
Unit of Measure: Categorical (Present/Absent)
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Day 1
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Radiographic Marginal Bone Loss (mm)
Prazo: Day 1
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Radiographic marginal bone level measured in millimeters as the distance from the implant reference point designed to be in intimate contact with the bone to the most coronal bone-to-implant contact on standardized periapical radiographs.
Unit of Measure: Millimeters (mm)
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Day 1
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Width of Keratinized Mucosa (KM, mm)
Prazo: Day 1
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Distance from the mucosal margin to the mucogingival junction at the buccal aspect of the implant, measured using a periodontal probe.
Unit of Measure: Millimeters (mm)
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Day 1
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Accessibility for Oral Hygiene Using an Interdental Brush
Prazo: Day 1
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Accessibility for oral hygiene will be clinically assessed at the selected implant in participants with peri-implantitis.
The peri-implant area will be classified as accessible when an interdental brush can be used to access the area for plaque removal and as non-accessible when the prosthetic design or surrounding structures prevent such access.
Unit of Measure: Categorical (Yes/No)
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Day 1
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Accessibility for Oral Hygiene Using an Interdental Brush
Prazo: Day 1
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Accessibility for oral hygiene will be clinically assessed at the selected implant in participants with peri-implantitis.
The peri-implant area will be classified as accessible when an interdental brush can be used to access the area for plaque removal and as non-accessible when the prosthetic design or surrounding structures prevent such access.
Unit of Measure: Categorical (Yes, No)
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Day 1
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History of Periodontitis
Prazo: Day 1
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A previous diagnosis of periodontitis will be determined by reviewing the participant's clinical history and dental records, based on the 2018 EFP/AAP classification criteria (interdental clinical attachment loss ≥1 mm at ≥2 non-adjacent teeth, or buccal/oral clinical attachment loss ≥3 mm with probing depth >3 mm at ≥2 teeth, and/or radiographic evidence of alveolar bone loss).
In patients treated for periodontitis, the endpoints of periodontal treatment will be taken into account, allowing probing depths up to 5 mm in the absence of bleeding on probing (BoP) or up to 4 mm in its presence.
Unit of Measure: Categorical (Present/Absent).
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Day 1
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Implant Surface
Prazo: Day 1
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Type of implant surface according to the manufacturer's specifications.
Unit of Measure: Categorical (Treated, Untreated)
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Day 1
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History of supportive periodontal maintenance
Prazo: Day 1
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Adherence to supportive periodontal maintenance therapy (≥2 professional maintenance visits per year) following periodontal treatment will be determined from the participant's clinical history and self-report.
Unit of Measure: Categorical (Present/Absent)
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Day 1
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Implant surface
Prazo: Day 1
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The surface treatment of the dental implant placed will be recorded from manufacturer specifications and surgical records.
Unit of Measure: Categorical (anodised; acid-etched; acid-etched and sandblasted).
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Day 1
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Prosthetic restoration type
Prazo: Day 1
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The type of prosthetic restoration supported by the implant will be recorded from clinical and prosthetic records.
Unit of Measure: Categorical (single crown; partial prosthesis; full-arch prosthesis; overdenture; screw-retained; cement-retained).
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Day 1
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Prosthetic framework material
Prazo: Day 1
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The material of the prosthetic framework will be recorded from clinical and laboratory records.
Unit of Measure: Categorical (titanium; zirconia; cobalt-chromium alloy).
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Day 1
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Age (years)
Prazo: Day 1
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Participant age at baseline (T0), calculated as the interval between the date of birth and the enrollment date.
Unit of Measure: Years, months, and days.
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Day 1
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Sex
Prazo: Day 1
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Self-reported sex of the participan.
Unit of Measure: Categorical (Male, Female, Other, Prefer not to disclose)
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Day 1
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Colaboradores e Investigadores
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 14/2025
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