Recent Advances in Dental
Hard Tissue Remineralization:
A Review of
Literature
Mando K Arifa, Rena Ephraim, and Thiruman Rajamani
Int J Clin Pediatr Dent. 2019 Mar-Apr; 12(2): 139–144
INTRODUCTION
Dental caries is a disease affecting the teeth characterized by demineralization
and cavitation
Caries is a cyclic event with periods of demineralizations and remineralization.
When the demineralization process predominates, it leads to cavitation
Demineralisation Remineralisation
Process involves loss of minerals Process is a natural repair
at the advancing front of the mechanism to restore the
lesion with the transport of acid minerals again, in ionic forms,
ions from the plaque . to the hydroxyapatite (HAP)
It occurs at critical ph 5.5 crystal lattice.
It occurs under near-neutral
physiological pH conditions
where calcium and phosphate
mineral ions are redeposited
within the caries lesion
Requirements of an ideal remineralization material are as follows:
i. Diffuses into the subsurface or delivers calcium and phosphate into the
subsurface
ii. Does not deliver an excess of calcium
iii. Does not favor calculus formation
iv. Works at an acidic Ph
v. Works in xerostomic patients
vi. Boosts the remineralizing properties of saliva
fluoride Non fluoride Arginine Electric field- Self-assembling biomimetics
induced peptides
remineralization
Alpha tricalcium Nanoparticles
phosphate (TCP) polydopamine PA
β-TCP
Calcium
Amorphous calcium
phosphate fluoride
nanoparticles
CPP–ACP
Sodium calcium Calcium
phosphosilicate phosphate-
(bioactive glass) based
Xylitol nanomaterials.
Dicalcium phosphate NanoHAP
dehydrate (DCPD) particles
ACP
nanoparticles
Nanobioactive
glass materials
FLUORIDE
Fluoride inhibits demineralization as the fluorapatite crystals formed by the
reaction with enamel apatite crystals, are more resistant to acid attack as
compared to hydroxyapatite crystals.
Fluoride enhances remineralization as it speeds up the growth of the new
fluorapatite crystals by bringing calcium and phosphate ions together.
It inhibits the activity of acid producing carious bacteria, by interfering with
the production of phosphoenol pyruvate (PEP) which is a key intermediate of
the glycolytic pathway in bacteria
Fluoride retains on dental hard tissue and in the plaque which leads to
decrease demineralization and enhances remineralization
Fluoride-containing Dentifrices-
i. Sodium fluoride (NaF2),
ii. Sodium monofluorophosphate (Na2FPO3 ),
iii. Amine fluoride (C27H60F2N2O3 ),
iv. Stannous fluoride (SnF2 ), or combinations of these
Fluoride varnishes
Tablets, lozenges
Mouth rinse
Gels
Foams
CALCIUM PHOSPHATE COMPOUNDS
Major components of hydroxyapatite crystals
Concentrations of calcium and phosphate in saliva and plaque play a key role
in influencing the tooth demineralization and remineralization processes
Remineralisation occurs when Ca:P ratio is 1.6 in plaque
i) β-TCP-
combination of tricalcium phosphate with fluoride can provide greater enamel
remineralization and build more acid-resistant mineral relative to fluoride
alone
But betaTCP is majorly used as bone grafts
e.g. cerasorb, bioResorp
ii) Functionalized TCP
Functionalized TCP is a low-dose calcium phosphate system that is
incorporated into a single-phase aqueous or non-aqueous topical fluoride
formulation.
It provides a barrier that prevents premature TCP–fluoride interactions and
also facilitates a targeted delivery of TCP when applied to the teeth
Available in toothpaste and varnish
E.g. Clinpro 5000 Anti-Cavity Toothpaste and Vanish 5% Sodium Fluoride White
Varnish
DICALCIUM PHOSPHATE DIHYDRATE
(DCPD)
DCPD is a precursor for apatite that readily turns into fluorapatite in the
presence of fluoride
DCPD in a dentifrice increases the levels of free calcium ions in the plaque
fluid, and these remain elevated for up to 12 hours after brushing
Wefel and Harless 1987 showed in vitro study that even a 1-ppm fluoride
solution could successfully and rapidly initiate remineralization of lesions
after three 2-min pretreatment rinses with a DCPD-forming solution
E.g. Pureen® AmLion Toothpaste
Amorphous Calcium Phosphate (ACP)
ACP act as two way delivery system to keep the calcium and phosphorous components
from reacting with each other before use. The sources of calcium and phosphorous are
two salts, calcium sulfate and dipotassium phosphate. When the two salts are mixed,
they rapidly form ACP that can precipitate onto the tooth surface. This precipitated ACP
can then readily dissolve into the saliva and can be available for tooth remineralisation
First described by Aaron S. Posner in 1963
Calcium
sulfate
ACP
precipitate
(crystalline
phase)
Readily dissolve in saliva,
Dipotassiu
m provide calcium and
phosphate phosphorus
Can be used as desensitizing agent
First developed by Dr. Ming in 1999
E,g. Enamelon( ACP+SnF2)
i) ACP-filled Composites-
ACP as a filler encapsulated in a polymer binder was introduced by Skrtic and
Antonucci
Releases calcium and phosphate ions into saliva and deposit into tooth
structures as an apatitic mineral, which is similar to the hydroxyapatite found
naturally in teeth and bone
E.g. Ariston pH control-introduced by Ivoclar- Vivadent Company
ii) ACP-CPP-
developed by Eric Reynolds and co-workers in 2009
CPP(casein phosphopeptide) is a milk derived protein
CPP–ACP when mixed together reacts to form the ACP material that
precipitates onto the tooth structure and elevates calcium levels in the
plaque fluid.
CPP also selectively inhibits the streptococcal species which favours the less
cariogenic species in the plaque
E.g. GC Tooth Mousse Plus™, Recaldent and MI Paste Plus
BIOACTIVE MATERIALS
A bioactive material is defined as a material that stimulates a beneficial
response from the body, particularly bonding to host bone tissue and to the
formation of a calcium phosphate layer on a material surface
Bioglass is a class of bioactive material which is composed of calcium,
sodium, phosphate and silicate.
Bioactive glass particles get deposited on dentine surface and occlude the
dentinal tubules by inducing the formation of carbonated hydroxyapatite-like
materials
NovaMin™(2002 by Dr. Len Litkowski and Dr. Gary Hack) is a bioactive glass
containing 45% SiO , 24.5% Na O, 24.5% CaO, and 6% P O
The new layer is called HCA ( hydroxyl carbonate
apatite layer)
E.g. BioMin
In India NovaMin is available as NUPRO Sensodyne Prophy Paste
NANOMATERIALS
Nanoparticles have better ion release profiles than microparticles.
These materials are often added to restorative materials as inorganic fillers,
such as resin composites to release calcium, phosphate, and fluoride ions for
remineralization of dental hard tissues
i) Calcium Fluoride Nanoparticles
Xu HHK et al. have shown that the addition of nanoCaF increases the
cumulative fluoride release compared to the fluoride release in traditional
glass ionomer cements because the CaF nanoparticle (nano-CaF ) has a 20-
fold higher surface area compared with traditional glass ionomer cements
E.g. Ketac N100 from 3M ESPE.
ii) Calcium Phosphate-based Nanomaterials
nanoparticles of HAP, TCP and ACP as sources to release calcium/phosphate
ions and increase the supersaturation of hydroxyapatite in carious lesions
iii) NanoHA Particles
First made by Sangi company of Japan in 1900
Nano-sized HA (n-HA) is similar to the apatite crystal of tooth enamel in
morphology and crystal structure. So it can be substituted for the natural
mineral constituent of enamel for repair biomimetically.
n-HA particles with a size of 20 nm fits well with the dimensions of the
nanodefects on the enamel surface caused by acidic erosion and the
nanoparticles can strongly attach to the demineralized enamel surface and
inhibit further acid attack.
E.g. Apagard™, Renamel™
XYLITOL
Tooth friendly nonfermantable sugar
alcohol which has been shown to have
noncariogenic as well as cariostatic
effects
It helps in inactivation of S. mutans
and inhibition of plaque's ability to
produce acids and polysaccharides
Stimulate salivary flow which results in
increased buffering capacity against
acids and high mineral content
remineralizes the damaged areas of
enamel
Milburn et al. have shown that fluoride varnish, containing xylitol-coated
calcium and phosphate, had the greatest initial fluoride release in the first
four hours, exceeding 10 times than that of other varnishes
BIOMIMETIC REMINERALIZATION OF THE
DENTIN AND ENAMEL
Biomimetic meaning is relating to or denoting synthetic methods which mimic
biochemical processes.
Biomimetic remineralization aims in attempting to backfill the demineralized
dentin collagen with liquid-like ACP nanoprecursor particles that are
stabilized by biomimetic analogs of noncollagenous proteins
Polydopamines-
oxidative polymerization of dopamine in aqueous solutions spontaneously
forms polydopamine which exhibits a strong adhesive property to collagen
In demineralized dentin, polydopamine binded to collagen fiber act as a new
nucleation site that will be favorable for HA crystal growth.
Proanthocyanidin (PA)
Grape seed extract (GSE) contains Proanthocyanidin (PA) and is reported to
strengthen collagen-based tissues by increasing collagen cross-links
It can form insoluble HA complexes when mixed with a remineralizing
solution
It is mostly combined with CPP amorphous calcium fluoride phosphate (CPP-
ACFP)
Self-assembling Peptide
Self-assembling peptides (P11-4) is used for regenerative treatment of early
caries lesions.
Products contain this peptide as the active ingredient
P11-4 monomers applied to an early caries lesion, diffuse into the subsurface
micropores of the lesion and assemble under high ionic strength into a 3D-
matrix (scaffold), which attracts calcium phosphate from saliva and templates
de novo hydroxyapatite crystal formation around the matrix, i.e., triggering
biomimetic mineralization that enables the regeneration of enamel and
dentin
This process takes several weeks to accomplish remineralization of the
treated lesion
Curolox® Technology is used
Available as Curodont™ Repair (Credentis AG, Windisch, Switzerland)
Electric Field-induced Remineralization
Wu in 2015 introduced this technique to remineralize the completely
demineralized dentin collagen matrix in absence of non collagenous proteins
He used calcium chloride agarose hydrogel, sodium hydrogen phosphate and
fluoride agarose hydrogel at 20 mA for 4 and 12 h in electrophoresis
Arginine Bicarbonate
Arginine bicarbonate is an amino acid complex with particles of calcium
carbonate
Toothpastes are available for caries control and hypersensitivity
Calcium carbonate particles adhere to the surface of the teeth.
Calcium carbonate dissolves slowly, the released calcium is available to
remineralize the mineral while the release of carbonate may give a slight
local pH rise .
Calcium carbonate carrier – SensiStat
The SensiStat technology is made of arginine, bicarbonate, an amino acid
complex, and particles of calcium carbonate, a common abrasive in
toothpaste.
The arginine complex is responsible for adhering the calcium carbonate
particles to the dentin or enamel surface and allows the calcium carbonate to
slowly dissolve and release calcium that is then available to remineralize the
tooth surface.
The SensiStat Technology was developed by Dr. Israel Kleinberg of New York
E.g. Colgate Sensitive Pro-Relief
CONCLUSION
The focus of restorative dentistry has always been towards a conservative
approach, out of which remineralization procedures are the most preferred
and optimal way of regeneration of lost tooth structure
Fluoride treatments are generally used for remineralising procedures but still
now ,continued efforts to increase the efficacy of fluoride is under great
research
Due to advent of new materials like bioglass and biomimetics a new area of
research has developed to that could bring out new materials for
remineralisation
THANK YOU
References
Amaechi, B.T. and Van Loveren, C., 2013. Fluorides and non-fluoride
remineralization systems. In Toothpastes (Vol. 23, pp. 15-26). Karger
Publishers.
Hegde, S., Roma, M. and Shetty, D., 2016. Non-Fluoridated Remineralization
Agents in Dentistry. Journal of Pharmaceutical Sciences and Research, 8(8),
p.884.
Skrtic, D. and Antonucci, J.M., 2016. Polymeric dental composites based on
remineralizing amorphous calcium phosphate fillers. Current trends in
polymer science, 17, p.1.
Xie, Q., Bedran-Russo, A.K. and Wu, C.D., 2008. In vitro remineralization
effects of grape seed extract on artificial root caries. Journal of
dentistry, 36(11), pp.900-906.
Amaechi, B.T., 2015. Remineralization therapies for initial caries
lesions. Current Oral Health Reports, 2(2), pp.95-101.
Wu, X.T., Mei, M.L., Li, Q.L., Cao, C.Y., Chen, J.L., Xia, R., Zhang, Z.H. and
Chu, C.H., 2015. A direct electric field-aided biomimetic mineralization
system for inducing the remineralization of dentin collagen
matrix. Materials, 8(11), pp.7889-7899.
Li, X., Wang, J., Joiner, A. and Chang, J., 2014. The remineralisation of
enamel: a review of the literature. Journal of dentistry, 42, pp.S12-S20.
Reynolds, E.C., 2008. Calcium phosphate‐based remineralization systems:
scientific evidence?. Australian dental journal, 53(3), pp.268-273.
