Genotoxicity Assessment of Dental Implants in Gingival Epithelial Cells

NCT ID: NCT04540991

Last Updated: 2020-09-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-10

Study Completion Date

2022-04-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Genotoxicity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

implant placement

Intervention Type PROCEDURE

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.

gingiva former placement

Intervention Type PROCEDURE

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.

Collecting gingival epithelial cellsusing the swab technique

Intervention Type DIAGNOSTIC_TEST

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).

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-.

Group Type ACTIVE_COMPARATOR

implant placement

Intervention Type PROCEDURE

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.

gingiva former placement

Intervention Type PROCEDURE

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.

Collecting gingival epithelial cellsusing the swab technique

Intervention Type DIAGNOSTIC_TEST

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).

Interventions

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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.

Intervention Type 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.

Intervention Type PROCEDURE

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).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Daniel Jerković

OTHER

Sponsor Role lead

Responsible Party

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Daniel Jerković

DMD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Daniel Jerkovic, DMD

Role: PRINCIPAL_INVESTIGATOR

University of Split, School of Medicine

Locations

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School of Medicine, University of Split

Split, , Croatia

Site Status

Countries

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Croatia

References

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Other Identifiers

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003-08/20-03/0005

Identifier Type: -

Identifier Source: org_study_id

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