Bioaktivni dentalni materijali - modulacija aktivne matrice radi unapređenja kliničke učinkovitosti i redukcije oštećenja DNK


Keywords: amorphous calcium phosphate (ACP); composite resins; fluorides; genotoxicity tests; orthodontics; polymerization.

Doctoral thesis of the research assistant Magda Trinajstić Zrinski; co-mentors professor Stjepan Špalj and Davor Želježić, will be completed within this project.

Caries is the most common, and also the most significant global public health issue at children and adolescents. Early caries in the shape of the white spot lesions of enamel is the most often side-effect of the orthodontic treatment. Due to the orthodontic appliances, which are often fixed to the teeth for a long period of time, it is more difficult to maintain satisfactory oral hygiene and regularly remove dentobacterial plaque. Good oral hygiene maintenance is possible, but is compromised in three quarters of the patients, due to the poor compliance. In order to avoid problems caused by the unsatisfactory patient cooperation, research and development is being shifted toward the modulation of the commercial and experimental composite dental materials with bioactive substances (fluorides, amorphous calcium phosphate (ACP)) which would be released through the prolonged time and had protective effect on enamel, but also enable the reparation of the initial enamel lesions through the remineralization. Poor oral hygiene causes disbalance in the pH of the oral cavity, which weakens the individual protective and reparative potential which leads to the damage of the hard dental tissues, but also affects the release of the biohazardous components of the adhesives (monomers, endocrine-mimetic pseudo estrogen bisphenol A). Composites modulated by bioactive materials (biomaterials) are being used for the restauration of the lost hard dental tissues and attachment of the orthodontic appliances for the teeth. They exhibit the bonding strength comparable to the conventional composites, but their efficiency in enamel remineralization has not been proven yet, although the latest research indicates the possible protective role. On the other hand, fluorides exhibit cytotoxic effect generating the oxidative stress, damage of the outer mitochondrial membrane and disturbance in the cell metabolism. Remineralization properties were also noticed for the ACP, currently investigated in experimental composites, who’s cytotoxic and genotoxic effects are still insufficiently explored.

Research on the subject of biocompatibility in orthodontics was mainly associated with the corrosion of the metallic parts of the orthodontic appliances, as well as the cytoxicity and genotoxicity in vitro. Research group from our Department of Orthodontics gave its contribution to this scientific field, mainly in research of the interaction of the alloys with the remineralizing agents based on the fluorides and casein-phospho-peptide-amorphous calcium phosphate (CPP-ACP), financed by the Croatian Science Foundation and the University of Rijeka grants. Our research up to date showed that adjuvant remineralizing solutions in form of gels and antiseptic mouthwashes induce more corrosion of the metal components of the fixed orthodontic appliances, accompanied by the increased leaching of the potentially allergenic nickel and titanium ions. Research area of the team from Department of Orthodontics by the means of this research project expands their interest to the non-metallic components of the orthodontic materials with adjuvants with protective and reparatory potential at initial carious lesions. Previous studies on cytotoxicity of the composite materials used for the adhesion of the orthodontic appliances onto the teeth showed unwanted effects of the certain commercial materials, however, preparation of the specimens in those studies did not simulate clinical setting. Research on the genotoxicity of the orthodontic composite adhesives are still insufficient. The research on genotoxicity of the materials is necessary for the assessment of the biocompatibility and safety for the patients. Considering the facts: the orthodontic composite adhesives stay in the patients’ mouth for a prolonged period of time; the well-known toxicity of the bis-methacrylic monomers; problems associated with light curing; fluoride content in some commercial materials; development of the experimental composites with the remineralizing adjuvant ACP, the assessment of the genotoxicity is necessary for determination of its possibly damaging biological effect.

Research which will be conducted during the duration of this grant will include different kinds of the organic phase of the composites and adjuvants of various bioactive substances, which influence the degree of conversion of the monomer into polymer. The hypothesis is that genotoxicity Is not primary dependent on the time-related degree of conversion during various light curing time (in duration of either 10 or 20 seconds), where smaller degree of conversion would be associated with higher genotoxicity; rather, it is associated with the materials’ composition, its’ organic and inorganic components, as well as addition and type of bioactive substances. This research will determine whether materials with higher share of carbonyl and carboxyl groups with unsaturated bonds at near end have greater potential to create epoxides and also greater genotoxicity. It will be determined whether both commercial and experimental orthodontic composite materials cause the DNA chain breakdown and micronuclei formation. The influence of the inert glass filling and bioactive filling materials on the degree of conversion and biocompatibility of commercial and experimental composite adhesives will be established through this research.

It is planned to conduct the Testing of the properties, protective and reparatory potential of orthodontic adhesive materials modulated with experimentally added fluorides, the ability to repeatedly recharge the adhesive in order to prolong time of effective activity, as well as the influence of the modulation on the alteration of clinical properties of the adhesives.

Influence of the disrupted balance of the pH of the oral cavity also affects the release of the biohazardous components of the adhesives (monomers, endocrine-mimetic pseudo estrogen bisphenol A, …); the qualitative and quantitative analysis of the released compounds will be conducted by the means of the liquid chromatography.

Modulation of the existing and experimental composite adhesives represents new step in translation of the current research into development and creation of the new dental materials for the clinical use, accompanied by the testing of all aspects which are important for the development of the new materials, in order to achieve the highest degree of biocompatibility.

Istraživački tim
Magda Trinajstić Zrinski
Stjepan Špalj
Miljanić Snežana
Želježić Davor
Marović Danijela
Contardo Luca
Dalibor Broznić
Peroš Kristina
Višnja Katić

Višnja Katić dr. dent. med.

Medicinski fakultet
Medicinski fakultet
Medicinski fakultet

prostorija: Krešimirova 40 /I.kat, ordinacija br.4

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