Immunological and Regenerative Implications of Corrosion of Dental Materials (IMUNODENT)

Immunological and Regenerative Implications of Corrosion of Dental Materials in Children and Adolescents

During orthodontic treatment intraoral corrosion results with release of nickel and titanium ions from orthodontic appliances in surrounding tissues. Those transported in the saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Nickel is one of the strongest contact allergens, present in numerous dental alloys. The aim of this project is to investigate the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistance of gingivitis to therapy, and bacterial resistance to antibiotics) and changes in performance of orthodontic appliances with repercussion on regeneration of bone and periodontal tissues.

Study Overview

• Status: Completed
• Conditions: Gingivitis; Caries; Enamel
• Intervention / Treatment: Combination product: Exposure to oral antiseptics or enamel remineralisation agent

Detailed Description

Tooth movement with appliances based on nickel and titanium has got great osteogenic potential and can regenerate deficient parts of alveolar bone and gingiva and rehabilitate compromised occlusal relations and a patient's masticatory function. Due to the extended duration of this therapy, different procedures are carried out and materials are applied for prevention and regeneration of damaged enamel and oral mucosa. The oral cavity may be considered a galvanic cell in which dental alloys act as electrodes, while saliva and oral preventive and regenerative agents act as electrolites. The interaction causes corrosion, reduction of elasticity and increase of stiffness of appliances, which may in turn result in excessive forces, a disruption of tissue regeneration and irreparable damage of tooth roots, surrounding alveolar bone, periodontal ligament, gingiva and pulp.

During the extended exposion, released corrosive products in surrounding tissues and those transported in saliva and blood may cause a series of side effects from hypersensitivity reactions and soft tissue proliferation to cyto and genotoxicity. Today, allergies are ever more frequent and arise earlier in life. A specific group are children and young adolescents in pubertal growth, a period in which the immune system develops. Nickel is one of the strongest contact allergens, present in numerous dental alloys. Nickel allergy is occurs in up to 28.5% of population and cannot be deemed as low potential risk anymore.

In contrast, titan was considered a biocompatible material of no allergic potential. However, there is an increase in the frequency of presentations of different hypersensitivity reactions to titan, especially in patients with pacemakers. Numerous patients with hip endoprostheses, stents, dental implans and orthodontic appliances are exposed to titan. Titan allergy may be the cause of unexplained cases of failure and rejection of dental implants. Nickel and titan could cause bacterial resistance to antibiotics which may complicate treatment of a series of infections that are more frequent in children and adolescents.

Regulations for safety of medical products regulate safety issues of materials through mandatory laboratory testing and expertise. However, the testing of interactions of these materials with newly formed materials for prevention of damage and regeneration of orodental tissues is not obligatory prior to the start of their commercial use. Such testing should be conducted by independent scientific insitutions and not by producers with direct commercial interest.

The aim of this project is to investigate:

1. the corrosion of dental materials and appliances based on nickel and titan (in saliva and due to interaction with probiotics, remineralising agents and antiseptics)
2. the immune potential of nickel and titan ions (development of allergies, changes in cariogenic potential of dental plaque, resistency of gingivitis to therapy, and bacterial resistance to antibiotics)
3. the effect of nickel and titan ions cellular level
4. changes in performance of dental appliances with repercussion on regeneration of bone and periodontal tissues.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Croatia
  • Rijeka, Croatia, 51000
    • University of Rijeka Faculty of Dental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with fixed orthodontic appliances
• must be able to do a mouthwash

Exclusion Criteria:

• patients allergic to fluoride agents and chlorhexidine gluconate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high concentration enamel remineralisation agent; first month brushing teeth three times per day: twice per day with high-fluorides gel (Mirafluor K gel cola 6150 ppm F pH 5.1) and once per day without toothpaste and fluoride gel next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm)	Combination product: Exposure to oral antiseptics or enamel remineralisation agent
Experimental: oral antiseptic; first month brushing teeth without toothpaste three times per day and using oral antiseptic chlorhexidine mouthwash (Curasept ADS 212 a 200ml 0,12%) twice per day next two months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm)	Combination product: Exposure to oral antiseptics or enamel remineralisation agent
No Intervention: Control; regular oral hygiene without exposure to oral antiseptic or high concentration enamel remineralisation agent three months brushing teeth three times per day with toothpaste containing low concentration of fluorides (1450 ppm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction of oral bacterial flora to oral antiseptics and dental remineralisation agents	Detection of change of count of Streptococcus mutans, sorbinus and salivarius and total bacterial count assesed by qPCR in the dental plaque before and after intervention in patients with fixed orthodontic appliances.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dental arch shape	Measuring anterior and posterior dental arch width (in millimeters), anterior depth and depth to width ratio in orthodontic patients wearing uncoated nickel-titanium 0.020''x0.020'' archwire on the day of putting the archwire and on the day of removing it.	90 days
Oral hygiene	Assessing accumulation of dental biofilm with Modified Silness and Loe Plaque Index (0-3; 0=no plaque and 3=continuous line of dental bacterial plaque more than 1 millimetre).	210 days
pH of dental biofilm	Measuring pH of dental biofilm (colorimetric test with pH scale range from 4 to 7).	210 days
Gingivitis	Assessing extent of gingivitis by Full Mouth Bleeding Score (percentage).	210 days
Corrosion of dental alloy	Potential of corrosion, passive film breakdown and repassivation (mV)	90 days
Surface roughness of dental alloy	Surface roughness assessed by Atomic Force Microscopy (nm)	90 days
Friction of dental alloy	Friction coefficient (no units)	90 days
Forces produced by dental alloy	Load and unload forces measured by three-point bend test (N)	90 days
Hardness of dental alloy	Vickers Pyramid Number (HV)	90 days
Stifness of dental alloy	Young's modulus and yield strength (GPa)	90 days
Elasticity of dental alloy	Modulus of resilience and springback ratio (MJ/m-3)	90 days

Collaborators and Investigators

• Sponsor: University of Rijeka
• Collaborators: Croatian Science Foundation
• Investigators: Principal Investigator: Stjepan Spalj, PhD, University of medicine Rijeka

Publications and helpful links

General Publications

• Belasic TZ, Pejova B, Curkovic HO, Kamenar E, Cetenovic B, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Angle Orthod. 2021 Jul 1;91(4):528-537. doi: 10.2319/052620-480.1.
• Zibar Belasic T, Zigante M, Perkovic V, Uhac M, Spalj S. Comparison of dental and periodontal condition of patients unexposed and exposed to metal orthodontic appliance. Book of Abstracts of the 7th international Congress of School of Dental Medicine University of Zagreb, Rovinj, Croatia, 21.-22.05.2021. Acta Stomatol Croat. 2021;55:213-6.
• Zibar Belasic T, Zigante M, Uhac M, Karlovic S, Jelovica Badovinac I, Spalj S. Influence of intraoral application of antiseptics and fluorides during orthodontic treatment on biomechanics of remodeling of dental arches. 8th Virtual World Congress of Dental Students - Abstract book. Zagreb, Croatia, 2020. p. 2.
• Cindric L, Mohar Vitezić B, Zigante M, Spalj S, Markova Car E. Changes of bacterial profile of dental biofilm during orthodontic treatment and influence of fluorides and chlorhexidine. South Eur J Orthod Dentofac Res. Conference proceedings - 1st Congress of the Faculty of Dental medicine, University of Rijeka, Croatia, October 1st-3rd 2020. Rijeka, Hrvatska, 2020. p. 55.
• Zibar Belasic T, Pejova B, Otmacic Curkovic H, Kamenar E, Cetenovic B, Spalj S. Intraoral application of antiseptics and fluorides during orthodontic treatment does not affect significantly corrosion and mechanical characteristics of nickel-titanium alloy in orthodontic appliances. Prvi kongres Fakulteta dentalne medicine Sveučilišta u Rijeci, Rijeka, 1-2.10.2020. Knjiga sažetaka. South Eur J Orthod Dentofac Res 2020;7:56.
• Zibar Belasic T, Mohar Vitezic B, Zigante M, Spalj S, Markova Car E. Supragingival biofilm composition changes during orthodontic treatment and chlorhexidine use. Book of Abstracts 97th Annual Congress of the European Orthodontic Society, Limassol, Cipar, 30.05.-03.06.2022.

Helpful Links

• all data concerning research project are available at link (Immune and regenerative implications of corrosion of dental materials in children and adolescents)
• all data concerning new project are available at link (Environmental factors and microbiological interactions in the structure of dental biofilm)

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Oral antiseptics; remineralisation agents
• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Gingivitis; Anti-Infective Agents; Anti-Infective Agents, Local
• Other Study ID Numbers: IP-2014-09-7500

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO