Mehmet Sarikaya, et al.
New Biogenic Dental Product Rebuilds Tooth
Enamel, Treats Cavities
A team of scientists at the University of Washington has developed
a new dental product that uses protein amelogenin-derived peptides
to remineralize tooth enamel and treat cavities...
The study authors accomplished this by capturing the essence of
amelogenin — a protein crucial to forming the hard crown enamel —
to design amelogenin-derived peptides that biomineralize and are
the key active ingredient in the new technology....
“These peptides are proven to bind onto tooth surfaces and recruit
calcium and phosphate ions,” said study co-author Deniz Yucesoy, a
doctoral student at the University of Washington.
The peptide-enabled technology allows the deposition of 10 to 50
micrometers of new enamel on the teeth after each use...
“Remineralization guided by peptides is a healthy alternative to
current dental health care,” said study’s lead author Professor
Mehmet Sarikaya, from the Department of Chemical Engineering and
the Department of Oral Health Sciences at the University of
ACS Biomater. Sci. Eng, March 9, 2018;
Biomimetic Tooth Repair: Amelogenin-Derived
Peptide Enables In Vitro Remineralization of Human Enamel.
Sami Dogan et al.
White spot lesions (WSL) and incipient caries on enamel surfaces
are the earliest clinical outcomes for demineralization and
caries. If left untreated, the caries can progress and may cause
complex restorative procedures or even tooth extraction which
destroys soft and hard tissue architecture as a consequence of
connective tissue and bone loss. Current clinical practices are
insufficient in treating dental caries. A long-standing practical
challenge associated with demineralization related to dental
diseases is incorporating a functional mineral microlayer which is
fully integrated into the molecular structure of the tooth in
repairing damaged enamel. This study demonstrates that small
peptide domains derived from native protein amelogenin can be
utilized to construct a mineral layer on damaged human enamel in
vitro. Six groups were prepared to carry out remineralization on
artificially created lesions on enamel: (1) no treatment, (2) Ca2+
and PO43– only, (3) 1100 ppm fluoride (F), (4) 20?000 ppm F, (5)
1100 ppm F and peptide, and (6) peptide alone. While the 1100 ppm
F sample (indicative of common F content of toothpaste for
homecare) did not deliver F to the thinly deposited mineral layer,
high F test sample (indicative of clinical varnish treatment)
formed mainly CaF2 nanoparticles on the surface. Fluoride,
however, was deposited in the presence of the peptide, which also
formed a thin mineral layer which was partially crystallized as
fluorapatite. Among the test groups, only the peptide-alone sample
resulted in remineralization of fairly thick (10 µm) dense
mineralized layer containing HAp mineral, resembling the structure
of the healthy enamel. The newly formed mineralized layer
exhibited integration with the underlying enamel as evident by
cross-sectional imaging. The peptide-guided remineralization
approach sets the foundation for future development of biomimetic
products and treatments for dental health care.
REAGENTS AND METHODS FOR MINERALIZATION OF TOOTH ENAMEL
Inventor(s): SARIKAYA et al.
Reagents and methods for whitening and remineralizing
teeth using biomineralizing peptides are described.
Accumulation of various chromogcns/discolorants, for example, food
and tobacco that come into contact daily onto tooth surfaces and
their subsequent penetration into deeper regions (dentin), cause
tooth discoloration. Furthermore, the process of aging, disease,
trauma, certain medications, certain congenital conditions, and
environmental effects can also cause teeth to become discolored.
Although discolored teeth do not cause health problems, since
bright white teem arc usually considered to be cosmetically
desirable, there is a great deal of interest in developing
compositions and methods for whitening teeth.
There arc several techniques for whitening or bleaching of teeth.
Professional whitening methods, also known as "in-clinic"
whitening strategics, arc considered presently as the most
effective methods. These in-clinic whitening strategies typically
involve the application of high-concentration peroxide products
(up to 35%) and other abrasive chemicals to the discolored area.
These peroxide species penetrate the stained area (up to
underlying dentin layer) and dissolve the accumulated discoloring
agents through an oxidation process. To achieve desired effects
more quickly, such oxidation reactions on teeth arc often assisted
with external laser light application, which heats up the reaction
site and thereby increases the rate oxidation reaction.
Furthermore, utilization of titanium dioxide up to 10% is often
preferred to facilitate these photo- catalytic reactions. Other
in-clinic whitening techniques involve superficially removing the
enamel layer with abrasive instruments or pumice followed by
treatment with additional caustic agents.
There arc several drawbacks of these in-clinic techniques. First
of all, the abrasive chemicals and peroxide agents causes enamel
demoralization and results with teeth sensitivity. In most cases
sorc/injurcd gums as well as bad taste of the product itself cause
much discomfort to the patients. Further, patients arc required to
make a clinic appointment to get this medical service.
Other existing products for at-home use contain considerably lower
concentrations of active oxidizing agents and, thus, arc generally
less effective than in- clinic whitening strategics and products.
Therefore, dramatic whitening effect can only be achieved by the
repeated applications of these reagents for several weeks. These
treatments often assisted with bleaching trays (night-guard) in
order to better localize bleaching products and, thereby, maximize
the whitening effect However, even though these at home products
contain active whitening agents in lower concentrations, similar
side effects as those associated with professional treatments arc
very common. In addition, there arc paint-on, at-home whitening
products, also known as "tooth varnishes", as well as whitening
strips intended to eliminate the need for dental trays. However,
these products require more frequent applications, usually 3-timcs
in a day, to complete whitening procedure. Finally, among the
variety of at-home use products, whitening toothpastes and gels
are the least effective form of whitening products due to their
short contact time with the tooth surfaces. Although bleaching
agent additives augment the effectiveness, the whitening effect is
primarily as a result of removal of surface stains via mechanical
action of brushing and other polishing ingredients (for example,
Dental caries is one of the major public health problems and it is
a highly prevalent disease among the global population. Incipient
caries and white spot lesions (WSL) as well as hypersensitivity,
arc the earliest clinical evidence of enamel dcmincralization and
dental caries. Dental caries occurs when tooth enamel is exposed
to acid produced by cariogenic bacteria. As a result, acid
diffuses into surface enamel and dissolves hydroxyapatite (HAp)
mineral. Due to its non-rcgenerative nature, enamel is unable to
heal and repair itself post-dcmincralization. Traditionally,
fluoride (F) has been used as the key agent in prevention of
caries. Fluoride functions primarily via topical mechanisms. It is
believed that fluoride forms a thin layer of new but harder
mineral, namely fluorapatitc (FAp) which is incorporated into the
existing HAp mineral on the tooth surface. There is a trend of
enhancing the rcmincralization effect of fluoride with calcium and
phosphate supplementation in high risk individuals. Although
controversial, the use of fluoride products remains the primary
treatment modality for caries prevention and rcmincralization,
with major limitations regarding the efficacy of these products
for the reversal or prevention of dental caries. Fluoride delivery
systems, therefore, arc not sufficient to overcome the high caries
risk especially in younger and elderly population.
There is presently an unmet need for tooth whitening and
mineralization methods and products that reduce or eliminate the
need for concentrated, abrasive oxidizing agents and attendant
side effects such as dcmincralization-associatcd tooth sensitivity
and gum line injuries.
SUMMARY OF THE INVENTION
Herein we provide methods and compositions for whitening teeth
where the natural color of teeth is restored and improved upon by
generating newly formed thin mineral layer on discolored tooth
surface using one or more biomineralizing polypeptides. Herein we
also provide methods and compositions for mineralizing teeth.
In a first aspect, the present application provides a method for
whitening teeth, comprising administering to a subject in need
thereof an amount effective to whiten the teeth of a
biomineralizing polypeptide. In some embodiments, the method for
whitening teeth comprises administering to a subject in need
thereof an effective amount of a composition comprising a
biomineralizing polypeptide. In some embodiments, the
biomineralizing polypeptide comprises an amino acid sequence
selected from the group consisting of:
(PGYIN(L/F)SYE(K/N) SHSQAIN(T/V)DRTA)|.,0(ADP5; SEQ ID NO: 13), or
a functional equivalent thereof. In some embodiments, the
biomineralizing polypeptide comprises the amino acid sequence
(PGYINFSYENSHSQAINVDRTA)i-io (ADP5H; SEQ ID NO: 15), or a
functional equivalent thereof. In some embodiments, the
biomincralizing polypeptide comprises the amino acid sequence...
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