Cumartesi, Eylül 25, 2021

Next Generation Biomimetic Hydroxyapitates

Next Generation Biomimetic Hydroxyapitates

With an emphasis on tooth health, oral care active ingredients have evolved significantly in the past decade. In these days, remineralizers are based on hydroxyapatite (HAP),
the mineral physiologically found in enamel and dentin, and its derivatives.

Tooth remineralization usually relies on two strategies: the first refers to fluoride-based actives, the latter to Ca++ and PO4 – sources.

The tooth is composed of a rich and constantly evolving mineral phase, characterized by the presence of HAP in enamel and dentin, where it represents, respectively, 97%
and 70% of total composition. The remineralization is the process by which the tooth mineral phase is constantly subject to a restoring phase, as a mechanism of physiological
homeostasis and balance against daily demineralization.

“Biomimetic” is a term pointing out the study of the formation, structure or function of biologically produced substances and biological mechanisms and processes, for the
purpose of synthesizing similar products
which mimic natural ones.

The following proposals meet the biomimetic concept through different modalities and efficiently respond to the functional requirements to counteract the onset of events
like caries, hypersensitivity and whitening boosting.

• Biomimetic hydroxyapatite,
• Fluorohydroxyapatite,
• Amorphous calcium phosphate functionalized with citrates, fluoride and carbonate ions.

The biomimetic HAP compositional analysis was carried through X-ray diffraction. Tests were carried out to evaluate its hypersensitivity reduction action through subjective
evaluation, when used in a toothpaste formulation at 5% on 50 subjects, two applications a day, for 28 days.

Subjective evaluation on a toothpaste containing biomimetic HAP at 4% were assessed to quantify its whitening action. In vivo tests were made on a toothpaste containing
biomimetic HAP and fluorhydroxyapatite at 6%, against a control reference containing a benchmark remineralizing active +1,500 ppm of fluoride. After a three day treatment on 45 people with positive anamnesis for hypersensitivity, a tactile stimulus was applied on subjects’ teeth through a blunt probe.

The hypersensitivity score was reported according to VAS (visual analogic scale): the score was given through ratings from 0 to 1 no pain, 2–3 for mild, 4–6 for moderate, and 7–10 for severe pain. SEM images were taken out of ex vivo tests on bovine teeth to observe the functionalized amorphous calcium phosphate (F-ACP) complex behavior.

The images are observable with different resolution (5.0 and 15.0K), the differences between teeth demineralized after acid treatment and after 1–2 week treatments with a toothpaste including 10% of F-ACP solution, to highlight the new mineral phase deposition on the tooth.

biomimetic HAP

surfaces improve  the biocompatibility

Previous studies confirmed that rough surfaces improve the biocompatibility and adhesion of the material, confirming the HAP capability to easily get linked to substrates like tooth biofilm glycoproteins and microlesions. The different surface nature differentiates stoichiometric and biomimetic HAP for their crystalline index, too.

The crystalline phase is more accentuated in the stoichiometric HAP, determining different reactivity: 10 substances with inferior crystalline nature, such as Biomimetic HAP, increase the release of Ca++ and PO4 – ions available for the remineralization cycle, intending for remineralization the capability of releasing such elements in the saliva on a balanced, pH dependent and time-prolonged basis. The Biomimetic HAP reactivity is a key element exploited for bone prosthesis design,11 underscoring its biocomatibility and safety.

Previous studies suggest HAP more efficiently promotes mineral deposition on the tooth in
comparison to benchmark Ca++ and PO4 – based materials. 13 The Biomimetic HAP presented here was subject to several tests to identify its chemical nature and functional features when included in toothpaste.

Below test, shows x-ray diffraction analysis comparison between biomimetic, physiological and stoichiometric HAP. Biomimetic HAP gives peaks comparable to the HAP expressed in the human body, confirming its mimic nature, particularly in relationship to the detection of CO3 – ions in the OH vacant sites.

This pattern is in contrast to the significantly different peaks observed with the stoichiometric form, suggesting significant differences in the compositional background of the product.

biomimetic, physiological and stoichiometric  HAP.

The reactive nature of biomimetic HAP explains its tendency to release in the saliva-remineralizing ions with a pH dependent mechanism: solubility tests highlighted very
low reactivity at pH values around 7.0, and a slow and steady release at values below 5.5, which are critical for demineralization.

Three different approaches in remineralization were taken under evaluation.

The biomimetic HAP with vacancies in OH sites showed suitability for daily oral care routine to promote a smart, balanced and long-lasting remineralization, aimed to prevent dental hypersensitivity, caries onset and promote tooth whitening effect boosting.

Hydroxyapatite, through biomimetic behavior given by its compatibility to the tooth surface in terms of adhesivity, shows great potential for applications on severe tooth microlesions, due to its resistance to acid attack and its enamel strengthening features, representing a state of the art treatment approach against caries and acid attack.

HAP complex, through a patented technology aimed to optimize the actives delivery on the tooth, allows to formulate anhydrous toothpaste specific for immediate tooth remineralization, and is indicated for professional and daily treatments following dental cleaning, or severe hypersensitivity or anti-caries treatments.

HAP complex

Nevin Ormancı