In-depth occlusion of dentine tubules via the application of (poly-L-aspartic acid)­strontium and phosphate/fluoride to treat dentine hypersensitivity.

Dentine hypersensitivity (DH) is a common oral health issue and occlusion of the exposed dentinal tubules (DTs) is regarded as the most effective therapeutic treatment nowadays. However, it is still difficult to develop easy and effective strategies for deep occlusion of DTs. In this study, we develop a strategy for occluding DTs deeply and compactly via simple application of occlusion media including (poly-L-aspartic acid)­strontium (PAsp­strontium) and phosphate/fluoride. The bonding of strontium ions to poly-L-aspartic acid formed a positively charged PAsp­strontium complexes. After application of 15 min each, the PAsp­strontium and phosphate/fluoride rapidly penetrated into the DTs in turn via the electrostatic interaction, then occluded the DTs with crystals up to a depth of 150 µm. The occlusion within DTs was resistant to abrasive and acidic challenges. The occlusion media performed better than commercial desensitizers Duraphat and Gluma. Moreover, this strategy possessed sufficient biocompatible and excellent performance in vivo. The application of occlusion media would shed light on in the management of DH.

Polyelectrolyte-Cation Complexes Using PAsp-Sr Complexes Induce Biomimetic Mineralization with Antibacterial Ability.

Remineralized dentin with an antibacterial ability is still a significant challenge in dentistry. Previously, a polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for rapid collagen mineralization. In the present study, the expansion concept of the PCCP process is explored by replacing the calcium with other cations, such as strontium. The results of transmission electron microscopy (TEM), 3D stochastic optical reconstruction microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and high-resolution TEM with selected area electron diffraction demonstrate that biomimetic mineralization of collagen fibrils and demineralized dentin could be fulfilled with Sr&F-codoped hydroxyapatite (HAp) after they are treated with poly-aspartic acid-strontium (PAsp-Sr) suspension followed by a phosphate&fluoride solution. Moreover, dentin remineralized with Sr&F-codoped HAp exhibits in vitro and in vivo antibacterial ability against Streptococcus mutans. The cytotoxicity and oral mucosa irritation tests reveal excellent biocompatibility of mineralization mediums (PAsp-Sr suspension and phosphate&fluoride solution). The demineralized dentin's mechanical properties (elastic modulus and microhardness) could be restored almost to that of the intact dentin. Hence, the expansion concept of the PCCP process that replaces calcium ions with some cationic ions along with fluorine opens up new horizons for generating antibacterial remineralized dentin containing ions-doped HAp with excellent biocompatibility via biomimetic mineralization technology.

Reversion of ACP Nanoparticles into Prenucleation Clusters via Surfactant for Promoting Biomimetic Mineralization: A Physicochemical Understanding of Biosurfactant Role in Biomineralization Process.

Amphiphilic biomolecules are abundant in mineralization front of biological hard tissues, which play a vital role in osteogenesis and dental hard tissue formation. Amphiphilic biomolecules function as biosurfactants, however, their biosurfactant role in biomineralization process has never been investigated. This study, for the first time, demonstrates that aggregated amorphous calcium phosphate (ACP) nanoparticles can be reversed into dispersed ultrasmall prenucleation clusters (PNCs) via breakdown and dispersion of the ACP nanoparticles by a surfactant. The reduced surface energy of ACP@TPGS and the electrostatic interaction between calcium ions and the pair electrons on oxygen atoms of C-O-C of D-α-tocopheryl polyethylene glycol succinate (TPGS) provide driving force for breakdown and dispersion of ACP nanoparticles into ultrasmall PNCs which promote in vitro and in vivo biomimetic mineralization. The ACP@TPGS possesses excellent biocompatibility without any irritations to oral mucosa and dental pulp. This study not only introduces surfactant into biomimetic mineralization field, but also excites attention to the neglected biosurfactant role during biomineralization process.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

In-Depth Occlusion of Dentinal Tubules and Rapid Remineralization of Demineralized Dentin Induced by Polyelectrolyte-Calcium Complexes.

Dentin hypersensitivity (DH) is triggered by external stimuli irking fluid flow through exposed dentinal tubules (DTs). Three commercially available desensitizing agents as control in this study only achieve limited occlusion depths of ≈10 µm in the DTs as well as scarce remineralization of demineralized dentin matrix. Herein, polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for managing DH that demineralized dentin with exposed DTs is rubbed with ultrahighly concentrated polyelectrolyte-calcium suspension (4 g L-1 -5.44 m) followed by phosphate solution (3.25 m), each 10 min, leading to heavy remineralization of demineralized dentin and compact occlusion of the DTs over 200 µm after 1 day of in vitro and in vivo incubation. For the first time, it is demonstrated that the PCCP process relies on the pH-dependent electrostatic attraction between electropositive polyelectrolyte-calcium complexes and electronegative inwalls of DTs comprised of collagen fibrils and hydroxyapatite crystals under alkaline condition. The PCCP process might shed light on a promising dentin desensitizing strategy for DH management via rapid in-depth DT occlusion and remineralization of demineralized dentin.

A Hydroxypropyl Methylcellulose Film Loaded with AFCP Nanoparticles for Inhibiting Formation of Enamel White Spot Lesions.

OBJECTIVE: This study investigated the effects of mineralizing film consisting of hydroxypropyl methylcellulose (HPMC) and amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs). MATERIAL AND METHODS: The AFCP nanoparticles and mineralizing film were prepared via nanoprecipitation and solvent evaporation, respectively. They were characterized with Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectrometry (ICP-AES), and fluoride ion selective electrode. Thirty-two human enamel slices (4 mm × 4 mm × 1.5 mm) were highly polished and randomly assigned to four groups: negative control (no treatment); pure HPMC film; mineralizing film; GC Tooth Mousse Plus® (contains 10% CPP-ACP and 0.2% NaF). Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, Micro-CT, SEM/EDX, and nanoindentation. RESULTS: The mineralizing film could sustain release of Ca, P and F ions over 24 h and maintain AFCP nanoparticles in metastable state over 8~12 h. During 4 weeks of pH cycling, the mineralizing film group exhibited least color change (∆E), mineral loss and lesion depth (120 ± 10 µm) among four groups (p < 0.05). SEM findings revealed that the porosities among enamel crystals increased in negative control and pure HPMC film groups after pH cycling, whereas in mineralizing film group, the original microstructure of enamel was well conserved and mineral deposits were detected between enamel prisms. Mineralizing film group demonstrated a least reduction of nanomechanical properties such as elastic modulus of 77.02 ± 6.84 GPa and hardness of 3.62 ± 0.57 GPa (p < 0.05). CONCLUSION: The mineralizing film might be a promising strategy for prevention and management of WSLs via inhibiting enamel demineralization and promoting enamel remineralization.

Therapeutic Management of Demineralized Dentin Surfaces Using a Mineralizing Adhesive To Seal and Mineralize Dentin, Dentinal Tubules, and Odontoblast Processes.

Dentin hypersensitivity is attributable to the exposed dentin and its patent tubules. We proposed the therapeutic management of demineralized dentin surfaces using a mineralizing adhesive to seal and remineralize dentin, dentinal tubules, and odontoblast processes. An experimental self-etch adhesive and a mineralizing adhesive consisting of the self-etch adhesive and 20 wt % poly-aspartic acid-stabilized amorphous calcium phosphate (PAsp-ACP) nanoparticles were prepared and characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy. After 60 acid-etched midcoronal dentin disks were treated with distilled water (control), a desensitizing agent (Gluma), the experimental self-etch adhesive, and the mineralizing adhesive, dentin permeability was measured and mineralization was evaluated by Raman, FTIR, XRD, TEM, and selected-area electron diffraction, irrespective of abrasive and acidic challenges. In vitro cytotoxicity of the adhesive and the mineralizing adhesive was assessed by Cell Counting Kit-8. The mineralizing adhesive possessed excellent biocompatibility. We proposed a hybrid mineralization layer composed of the light-cured mineralizing adhesive and the mineralized dentin surfaces, as well as interiorly mineralized resin tags and odontoblast processes inside of the dentinal tubules. This hybrid mineralization not only reduced dentin permeability but also resisted abrasive and acidic attacks.