Abstract

Based on natural principles, we developed a novel toothpaste, containing morphogenetically active amorphous calcium polyphosphate (polyP) microparticles which are enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550 ± 120 nm), prepared by co-precipitating soluble Na-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a base toothpaste at a final concentration of 1% or 10%. The “a-polyP/RA-MP” ingredient significantly enhanced the stimulatory effect of the toothpaste on the growth of human mesenchymal stem cells (MSC). This increase was paralleled by an upregulation of the MSC marker genes for osteoblast differentiation, collagen type I and alkaline phosphatase. In addition, polyP, applied as Zn-polyP microparticles (“Zn-a-polyP-MP”), showed a distinct inhibitory effect on growth of Streptococcus mutans, in contrast to a toothpaste containing the broad-spectrum antibiotic triclosan that only marginally inhibits this cariogenic bacterium. Moreover, we demonstrate that the “a-polyP/RA-MP”-containing toothpaste efficiently repairs cracks/fissures in the enamel and dental regions and reseals dentinal tubules, already after a five-day treatment (brushing) of teeth as examined by SEM (scanning electron microscopy) and semi-quantitative EDX (energy-dispersive X-ray spectroscopy). The occlusion of the dentin cracks by the microparticles turned out to be stable and resistant against short-time high power sonication. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP microparticles enriched with retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity. While the polyP microparticles function as a sealant for dentinal damages and inducer of remineralization processes, the retinyl acetate acts as a regenerative stimulus for collagen gene expression in cells of the surrounding tissue, the periodontium.

Highlights

  • Teeth, as complex organs, are composed of two separate specialized hard tissues, dentin and enamel; they form an integrated attachment unit with bone via the specialized, periodontal ligament.Teeth are ectodermal organs that develop through sequential and reciprocal interactions between oral epithelial cells and the cranial neural crest derived mesenchymal cells

  • The results summarized in the present study show that the amorphous polyphosphate (a-polyP)-containing toothpaste efficiently repairs cracks in the enamel, reseals dentinal tubules of the dentin and efficiently inhibits growth of S. mutans; we termed this formula “dentoResealTM”

  • 2 mL retinyl acetate oil were dissolved in 100 mL ethanol and added to 20 g of the Ca2+ -polyP microparticles

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Summary

Introduction

As complex organs, are composed of two separate specialized hard tissues, dentin and enamel; they form an integrated attachment unit with bone via the specialized, periodontal ligament.Teeth are ectodermal organs that develop through sequential and reciprocal interactions between oral epithelial cells (ectoderm) and the cranial neural crest derived mesenchymal cells. As complex organs, are composed of two separate specialized hard tissues, dentin and enamel; they form an integrated attachment unit with bone via the specialized, periodontal ligament. Ameloblasts form the enamel, while the mesenchymal cells form all the other differentiated cells, such as the dentin forming odontoblasts. Teeth enamel and dentin are composed of biogenic apatite, but lack cells. Enamel and dentin are primarily composed of hydroxyapatite (HA) crystals. Enamel almost exclusively consists of an inorganic matrix (96% (w/w)) with only very little organic constituents (proteins and lipids) and of water (4%, (w/w)); the latter components occupy the gaps along the apatite crystals. In enamel the HA crystals have a hexagonal morphology and are bundled to form ≈4 μm diameter rods. The overall calcium and phosphorus (as phosphate) content of the teeth ranges between 34% to 39% (w/w) and

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