Genotoxicity Assessment of Dental Implants in Gingival Epithelial Cells

September 1, 2020 updated by: Daniel Jerković

Due to the strong correlation between genotoxicity and carcinogenesis, it is necessary to clarify the potential genotoxic effects of titanium dental implant systems. As most dental materials release small amounts of several elements into the oral cavity, proper regulations have to guarantee that the concern from genotoxicity/mutagenicity of dental materials is annulated or at the lowest possible level. Thus, further biocompatibility records are needed in order to evaluate the comprehensive risks of these compounds. In a view of the above-mentioned data, the aim of this in vivo study is to evaluate genotoxic and cytotoxic potential of implants and gingiva formers from two different implant systems in gingival epithelial cells.

Exfoliated gingival cells will be taken from 80 participants before and after 90 days of dental implant insertion, and 21 days following gingiva former placement. DNA damage will be analyzed using the micronucleus test. Tested dental implants will be Ankylos and Dentium, with corresponding gingival former.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Patients are divided into two groups depending on the dental implant system used in the therapy. Ankylos dental implants (Dentsplay Sirona, Charlotte, USA) are used in the first group of patients and Dentium SuperLine (Dentium Co., Seoul, Korea) in the second group.

The implants are placed in accordance with each implant system manufacturer's instructions and the treatment were performed according to the patient's standards and indications. Surgical procedures on all patients are performed by the same operator with the same surgical approach, protocol and instrumentation.

The surgeries are performed under local anesthesia and systemic antibiotics were given according to standard procedure. To ensure post-surgical oral hygiene, patients are advised to rinse the oral cavity with chlorhexidine until the day of sutures' removal. The sutures are removed10 day after implantation. The implants are healing by being submerged for 12 weeks based on the surgeon's clinical judgment, indications given and the need and preference of the patients. After healing, gingiva formers are placed.

Sample collection and a micronucleus assay in gingival epithelial cells To reduce individual variations, patients are observed longitudinally and each subject is served as their own control. Samples of gingival epithelial cells are collected from each participant's implementation site using the swab technique at three different time points: a control swab is taken just before the placement of the dental implant (T0); the second swab is taken 90 days after implantation meaning immediately before placement of the gingiva former (T1); and the third swab is taken 21 days after placement of the gingiva former (T2).

One hour before the sampling, the participants abstain from consuming any food and drinks. After rinsing of the oral cavity 3 times with tepid water to remove exfoliated cells, a T0 swab is taken by gently brushing the gingiva around place indicated for implant placement and later T1 and T2 around implant with a cytobrush (Cytobrush Plus; GmbH. Dietramszell-Linden, Germany). The samples are subsequently applied to coded laboratory glass slides.

The cells applied to microscopic slides are allowed to air-dry and fixed in methanol (80% v/v) at 4°C for 20 minutes. Staining is conducted with 5% Giemsa solution for 10 minutes. Afterward, the slides are rinsed with aqua distillate and air dry. The slides are examined under Olympus CX40 light microscope (Olympus. Tokyo. Japan) with 400× magnification, and each micronucleus and other nuclear anomalies are additionally verified under 1000× magnification. Two replicate slides are prepared for each subject and 1000 epithelium cells per preparation were analyzed for each sampling time.

Nuclear anomalies, such as micronucleus, karyorrhexis (nuclear disintegration indicating apoptosis), karyolysis (dissolution of the nucleus mostly indicating necrosis and apoptosis), pyknosis (nuclear shrinkage due to apoptosis), condensed chromatin (DNA complexed with proteins and apoptosis), nuclear buds (precursors of micronuclei, or high density of DNA repair complexes) and broken eggs (nuclei that appear cinched, binucleated cells (indicating impaired velocity of cell proliferation)) are estimated and qualified.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Split, Croatia, 21000
        • School of Medicine, University of Split

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • absence of a single tooth in the mandibular molar or premolar region
  • belonging to ASA I or ASA II group
  • absence of titanium hypersensitivity
  • absence of prosthetic restoration/replacement or orthodontic appliances in the oral cavity, -absence of oral precancerous lesions
  • no history of radiation in the head and neck area
  • absence of bisphosphonates and corticosteroids used in therapy.

Exclusion Criteria:

  • presence of systemic disease (e.g. uncontrolled diabetes, oral mucosal diseases, untreated gingivitis and periodontitis, endodontic lesions)
  • pocket depths ≥ 4 mm on adjacent teeth
  • bruxism
  • poor oral hygiene
  • pregnant and lactating women
  • taking of antibiotics in the last three months
  • taking any other pharmaceutics that have been proved to elevate DNA damage,
  • underwent medical radiation diagnostics
  • using mouthwash that contain alcohol
  • history of radiation in the head and neck area.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ankylos dental implant group
Patients are divided into two groups depending on the dental implant system used in the therapy. Ankylos dental implants (Dentsplay Sirona, Charlotte, USA) areused in the first group of patients.
Procedure: implant placement
The implants are placed in accordance with each implant system manufacturer's instructions and the treatment were performed according to the patient's standards and indications. Surgical procedures on all patients are performed by the same operator with the same surgical approach, protocol and instrumentation.
Procedure: gingiva former placement
Gingiva former are placed in accordance with each implant system manufacturer's instructions and the treatment were performed according to the patient's standards and indications. Surgical procedures of oppeninf implant cower and gingiva former placement on all patients are performed by the same operator with the same surgical approach, protocol and instrumentation.
Diagnostic test: Collecting gingival epithelial cellsusing the swab technique
Samples of gingival epithelial cells are collected from each participant's implementation site using the swab technique at three different time points: a control swab is taken just before the placement of the dental implant (T0); the second swab is taken 90 days after implantation meaning immediately before placement of the gingiva former (T1); and the third swab is taken 21 days after placement of the gingiva former (T2).
Active Comparator: Dentium SuperLine implant group
Patients are divided into two groups depending on the dental implant system used in the therapy. Dentium SuperLine implants (Dentium Co., Seoul, Korea) is used in the second group of patients-.
Procedure: implant placement
The implants are placed in accordance with each implant system manufacturer's instructions and the treatment were performed according to the patient's standards and indications. Surgical procedures on all patients are performed by the same operator with the same surgical approach, protocol and instrumentation.
Procedure: gingiva former placement
Gingiva former are placed in accordance with each implant system manufacturer's instructions and the treatment were performed according to the patient's standards and indications. Surgical procedures of oppeninf implant cower and gingiva former placement on all patients are performed by the same operator with the same surgical approach, protocol and instrumentation.
Diagnostic test: Collecting gingival epithelial cellsusing the swab technique
Samples of gingival epithelial cells are collected from each participant's implementation site using the swab technique at three different time points: a control swab is taken just before the placement of the dental implant (T0); the second swab is taken 90 days after implantation meaning immediately before placement of the gingiva former (T1); and the third swab is taken 21 days after placement of the gingiva former (T2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cytotoxic and/or genotoxic
Time Frame: 1 year
Evaluation of the cytotoxic and genotoxic alterations in gingival epithelial cells after application of titanium-based dental implant system
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daniel Jerković

Investigators

  • Principal Investigator: Daniel Jerkovic, DMD, University of Split, School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2020

Primary Completion (Anticipated)

March 20, 2021

Study Completion (Anticipated)

April 25, 2022

Study Registration Dates

First Submitted

September 1, 2020

First Submitted That Met QC Criteria

September 1, 2020

First Posted (Actual)

September 7, 2020

Study Record Updates

Last Update Posted (Actual)

September 7, 2020

Last Update Submitted That Met QC Criteria

September 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 003-08/20-03/0005 (Other Identifier: University of Split School of Medicine)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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