REMINERALISING AGENTS

GUIDED BY
Dr. KARUNAKAR
Dr. RAJI VIOLA SOLOMON
Dr. SHANTHIPRIYA

PRESENTED BY
T.PALLAVI
PG 1st YEAR
CONTENTS

 INTRODUCTION
 HISTORY
 STRUCTURE AND COMPOSITION OF HARD TISSUES OF TEETH
i. ENAMEL
ii. DENTIN
iii. CEMENTUM
 ROLE OF CALCIUM AND PHOSPHATE IN TEETH
 DEFINITION OF DEMINERALISATION AND REMINERALISATION
 FACTORS AFFECTING DE/REMINERALISATION
 DISTURBANCES IN MINERAL METABOLISM
 RATIONALE OF DEMINERALISATION AND REMINERALISATION
 DEMINERALISATION PROCESS
 REMINERALISATION PROCESS
 CHALLENGES POSED FOR REMINERALISING AGENTS
 IDEAL REQUIREMENTS OF REMINERALISING AGENTS
 REMINERALISING AGENTS
 RECENT ADVANCES IN REMINERALISING AGENTS
 CLINICAL SIGNIFICANCE
 REVIEW OF LITERATURE
 CONCLUSION
 REFERENCES
 INTRODUCTION

 Dental caries is one of the most common preventable childhood disease and
people are susceptible to the disease throughout their lifetime.
 Caries in Latin means, ‘rotten’
 It is the primary cause of oral pain and tooth loss.
 Though it can be arrested and potentially reversed in its early stages, it is often
not self-limiting and without proper care, caries can progress until the tooth is
destroyed .
 It is a multifactorial disease that starts with microbiological shifts within the
complex biofilm and is affected by
 Dental caries pathophysiology is not simply
a continual cumulative loss of tooth
minerals.
 It is rather a dynamic process characterized
by alternating periods of demineralization
and remineralization.
 Not all mineral loss from tooth structure
leads to

dental caries disease.

 HA Crystals at the tooth surface regularly go through natural periods of

mineral loss (demineralization) mineral gain (remineralization),

 HISTORY

 1980s - fluoride can cause remineralization of demineralized enamel

 Fazzi et al (1997) - demonstrated the formation of fluorapatite crystals
 Duggal et al - Reduced acid solubility of fluorapatite because of lower
carbonate content.
 Signs of toxicity shown by high fluoride content in systemic fluoride and
dentifrices which led to development of nontoxic fluoride alternatives as
effective remineralizing agents.
 The phenomenon of remineralization was first described by Head in 1909
 supported by Sounder and Schoonover in 1914 by invitro rehardening of
softened dentin
 In early 1960 - MASSLER, FUSAYAMA & BRANSTORM were the first who dealt
with the science of De / Remineralization.
STRUCTURE AND COMPOSITION OF
HARD TISSUES OF TEETH
ENAMEL
 Dental enamel is the highly mineralised tissue .

COMPOSITION:

COMPONENTS

 calcium phosphate in the form of hydroxyapatite

crystals.
 Small amounts of carbonate, Mg, K, Na and F
 Amelogenins - 90%
 Non-amelogenins - 10%
 Amelogenins are removed during enamel’s
development
 non amelogenin proteins persist in fully
mineralized tissue
 These substitutions in the crystal surface are beneficial to the tooth surface
because the new, matured tooth surface is less soluble and more resistant to
caries challenges.
 DENTIN

 Dentin provides the bulk and general form of the tooth

 is characterized as a hard tissue with dentinal tubules throughout its
thickness.

BY WEIGHT BY VOLUME COMPONENTS

Inorganic material – 70% Inorganic material - 45 % hydroxyapatite

Organic material- 20% Organic material – 33% type I collagen with

fractional inclusions of
glycoproteins,
proteoglycans and
phosphoproteins
Water – 10% Water – 22%
 CEMENTUM

 Cementum is the mineralized dental tissue covering the anatomic roots of

human teeth.
 It begins at the cervical portion of the tooth at the cemento enamel junction
and continues to the apex.
 Chemical composition is based on dry weight
 45% to 50% inorganic substances and
 50% to 55% organic material and water.
when the cementum or dentin is exposed to the oral environment after gingival recession.

A similar posteruptive maturation process is expected to occur on exposed root surfaces

Cementum is typically lost quickly as a result of wear forces such as toothbrushing and
scaling/root planning.

The highly porous and soluble newly exposed dentin undergoes similar demineralization
and remineralization cycles, thus creating a much less porous dentinal surface containing
larger amounts of minerals, particularly calcium, phosphate, and fluoride.

This increases crystal size and concentration ,significantly reduces the permeability and
caries susceptibility of the root surface, as happens in enamel.
 ROLE OF CA AND P IN TEETH

 Calcium, phosphate, and fluoride ions play an important role in the battle
between demineralization and remineral­ization processes
 They accordingly modify the susceptibility of tooth to caries progression .
 During demineralization, calcium release precedes phosphate release from
enamel, dentin, and cementum.
 Therefore, using calcium rather than phosphate to suppress the
demineralization process would be effective.
 DEFINITIONS

DEMINERALISATION:
 Demineralization is the process of removing minerals ions from HA crystals of hard
tissues, for example, enamel, dentin, cementum, and bone.
 Demineralization is defined as the process of removing minerals, in the form of
mineral ions from dental enamel.
- Silverstone (1977)
REMINERALISATION:
 It is the process whereby partially demineralized enamel is repaired through the
recrystallization of tooth enamel mineral salts
-(Silverstone 1977)
 Remineralization is defined as the process whereby calcium and phosphate ions are
supplied from a source external to the tooth to promote ion deposition into crystal
voids in demineralized enamel to produce net mineral gain.
The Role of Remineralizing Agents Used in Dentistry: An Update Then and Now Dr. Shakir Hussain Rather, Dr. Sajedabanu Kazi, Dr.
Safikabanu Kazi
 Both processes occur on the tooth surface, and a
substantial number of mineral ions can be lost
without destroying its integrity .

 Lacking of the integrity of HA latticework,

however, produces cavities.
 Demineralization is a reversible process; hence, the
partially demineralized HA crystals in teeth can
grow to their original size if they are exposed to oral
environments that favor remineralization
Contributing Factors to DM / RM Balance

Destabilizing factors Protective factors

Diet plaque = plaque acids Salivary buffering capacity

 in salivary flow Ca2+ and PO43-

 buffering Buffering & Rm

Acidic saliva
Fluoride contact - topical
Erosive acids
FACTORS EFFECTING DE/REMINERALISATION
1.ROLE OF ORAL ENVIRONMENT
 Role of plaque
 Role of saliva
 Role of diet
2.ROLE OF FLOURIDES/REMINERALISING AGENTS
3. ROLE OF ANTICARIOGENIC RESTORATIVE MATERIALS
4. ROLE OF DRUGS/XEROSTOMIA/AGE/SYSTEMIC DISORDERS AND OTHERS
DENTAL PLAQUE
Firmly adherent bio-film formed by microbial
colonization of pellicle.

Composition:
Two main compartments
 Extracellular phase- contains an aqueous phase called the plaque fluid
which is in direct contact with enamel & responsible for chemical
reactions at this interface.
 Cellular phase – major component is protein IgA, IgG, salivary proteins
& plasma type proteins are present
Role of Plaque
 Participates in repair & protection of enamel surface.
 Negative charge of enamel surface when immersed in saliva - immediately neutralized
by a layer of ions of opposite charge.
 Layer-called the Hydration layer or “Stern Layer”,
 consists mostly of calcium (90%) and phosphate (10%).
 Composition varies with the pH, ionic strength and the type of ions present in the
solution
Role Of Saliva
 Prevention of dental caries
 Provides calcium, phosphate, proteins, lipids, antibacterial substances, and buffers.
 if there is normal salivary flow (>0.7 ml/minute)\

 lower the risk of cavity formation

THE CRITICAL pH

The ‘critical pH’ is the pH at which a solution is just saturated with respect to a particular
mineral. For the HA crystal, it is approximately 5.5–6, below which the enamel disintegrates.

As the fluid surrounding the tooth becomes  acidic

a point is reached when it ceases to be supersaturated and

any further  in pH results in mineral dissolution.

 STEPHANS CURVE
 Critical pH for hydroxyapatite = 5.3- 5.5
 Critical pH for fluorapatite = 4.5
 Fluorapatite is less soluble than
hydroxyapatite.
 “critical pH” for dentin is = 6.2 – 6.7
ROLE OF DIET
 Frequent ingestion of sucrose – provides stronger potential for colonisation
by S.mutans , enchancing demineralisation
 Mature plaque exposed to this frequent sucrose rapidly metabolises to
organic acids

prolonged decline in Ph
Role of Fluorides/remineralising agents
 Reduce dental caries.
 By inhibiting mineral loss at the crystal surfaces and by enhancing the rebuilding or
remineralization of calcium and phosphate in a form more resistant to subsequent
acid attack.
ROLE OF DRUGS/XEROSTOMIA/AGE/SYSTEMIC
DISORDERS AND OTHERS
 Salivary flow and oral clearance rate influence the removal of food debris
and microorganisms.
 Decreased secretion of saliva (xerostomia or dry mouth) can occur due to:
 Certain drugs like antihistaminics, antidepressants, antihypertensives,
antipsychotic drugs, hypnotics, anticholinergics and diuretics.
 Withdrawal of the drug is followed by a return to normal salivation.
 Therapeutic irradiation of head and neck
 From prolonged stress

 Certain systemic conditions like diabetes mellitus, Sjogrens syndrome, liver

and pancreatic disturbances.
 With an individual's advancing age, the proportional volume of fat and
fibrovascular tissue increases in both the parotid and submandibular glands, while
the proportional volume of acini is reduced.
 No changes were observed in the number of duct.
 Thus, with increasing age, more and more of the functional parenchyma will be
replaced by connective tissue and fat and as a result salivary flow decreases.
 CLINICAL RELEVANCES:
 When saliva flow is reduced, oral health problems such as demineralization and
dental caries may develop.
 In these patients usage of remineralising agents are benefical.
ROLE OF ANTICARIOGENIC RESTORATIVE
MATERIALS
 Traditional glass ionomer cements
 high viscosity GICs,
 cermet cements,
 Resin modified glass ionomer cements (RMGICs)
 nanoionomer cements,
 compomers,
 glass carbomers,
 giomers; and
 composite resins contain fluorides
and they exhibit anticariogenic property.
 CLINICAL SIGNIFICANCE
 These restorative materials release an adequate amount of fluoride into the
oral environment and
 increase the level of fluoride in saliva, plaque and hard dental tissues
 Fluoride released from restorative materials effectively prevent the formation
of secondary caries.
DISTURBANCES IN MINERAL METABOLISM

 Tooth enamel is composed primarily of hydroxyapatite (HA)—

Ca10(PO4)6(OH)2 
 Oral fluid is a rich reservoir of calcium, phosphate, and fluoride minerals.
 According to the law of saturation, a dynamic equilibrium  exists between
the mineral contents of the tooth and the oral fluid
 The mineral content in the HA crystal = the oral fluid.
 At ‘neutral pH,’ the HA crystal dissolves minimally and

releases the (Ca2+), (PO43−) and (OH−) ions into the solution.
 If the solution, for instance, is the oral fluid that already contains the same
minerals, it becomes ‘supersaturated’, resulting in the ‘precipitation’ of the
minerals back onto the tooth enamel.
 At ‘acidic pH,’

(PO4)3−and (OH−) + (H+) (tooth–biofilm )

HPO42− and H20.
 In a severe acidic environment

(H+) + HPO42− H2PO42−, a more acidic ion.

 Thus oral fluid becomes ‘undersaturated’ with respect to the phosphate ions
(PO4 3−).
 This leads to the ‘dissolution’ of HA crystals in an attempt to resaturate the oral
fluid. This dissolution reaction is described as follows:
 Thus, it is evident that the dissolution of the HA crystals occurs at a certain
acidic pH, which is referred as being ‘below the critical pH of HA.’
RATIONALE FOR DEMINERALISATION AND
REMINERALISATION
 The chemical reactions of de- and remineralization are also explained in
relation to the ‘ion activity product’ (IAP in the solution) vs. ‘Ksp’ (Solubility
product constant of enamel
 The IAP denotes the product of the activity of the ions released into the
solution during dissolution and is expressed with regards to HA crystals as

(Ca2+)10 × (PO43−)6 × (OH−)2.

 IAP = (Ca2+)10(PO43)6(OH)2
 The Ksp for HA at 37 degree C is 7.41 × 10−60mmol/l
 When the IAP = Ksp,
 the solution is in equilibrium with the solid and is said to be saturated with respect to
the solid .
 Demineralization occurs when IAP in the solution < Ksp, and remineralization
occurs when IAP in the solution > Ksp.
 This reaction leads to release of mineral ions into the solution.
 Ca10(PO4)6(OH)2 + 14 H+ → 10 Ca+ + 6 H2PO4+ H2O
 The subsurface lesion is reversible via a remineralization process
 This is by the increase in oral fluid calcium and phosphate that drives the remineralization process.
 Sugars (sucrose, glucose, fructose) are converted to acids in the biofilm.
 When the pH decreases to below 5.5, undersaturation happens with respect to hydroxyapatite (HA),
resulting in mineral dissolution.
 Enamel demineralization and remineralization in the
presence of (F) Fluoride in dental biofilm:
 It is interesting to note that the entire demineralization and remineralization
process is limited to only few millimeters of superficial enamel.
 The ‘subsurface’ enamel is always in a demineralized state with a minimum of
0.03 mm of intact surface enamel.
 The reason for this is the inadequate penetration of the mineral ions during
precipitation.
 DEMINERALISATION PROCESS

Teeth are composites comprised of the phosphate-based mineral HA in the enamel, collagen
in the dentine, and living tissues.

Exposed to food, drink, and the microbiota of the mouth, teeth have developed a high
resistance to localized demineralization

This resistance is chiefly due to the enamel layer that covers the crown of the teeth.

Chemical dissolution of teeth is caused by acidic attack through two primary means: dietary
acid consumed through food or drink and microbial attack from bacteria present in the
mouth.

During an acidic attack, or a typical demineralization regime, chemical dissolution of both the
organic and inorganic matrix components takes place.
 REMINERALISATION PROCESS

saliva is considered one of the most important biological factors for neutralizing effects of acid exposure.

saliva acts as a constant source for calcium and phosphate

that helps in maintaining supersaturation with respect to tooth minerals,

therefore inhibiting tooth demineralization during periods of low pH, and

they promote tooth remineralization when the pH returns to neutral state

 Furthermore, when saliva secretion is stimulated, a rapid rise in pH to above neutrality occurs.

As a result a complex of calcium phosphate and glycoprotein called salivary precipitin is formed.

This complex is readily incorporated into dental plaque.

Due to its high solubility of calcium phosphate in salivary proteins (eight to ten times higher than calcium phosphate in tooth),

it serves as a sacrificial mineral, ie, reducing demineralization.

It also acts as a source of calcium and phosphate ions that are required for remineralization of decalcified tooth.

Saliva constantly delivers fluoride to the tooth surface; salivary fluoride is a key player in preventing tooth demineralization and
enhancing remineralization .
CHALLENGES POSED BY REMINERALIZING AGENTS

 There are several challenges to establishing the clinical effectiveness of

remineralization agents:
1. must demonstrate a benefit over and above an established and highly
effective agent, namely, fluoride.
2. must provide a remineralizing benefit in addition to the natural
remineralizing properties of saliva.
3. Should not favour calculus formation.
Ideal Requirements of Remineralizing Material
 Should deliver calcium and phosphate into the sub‑ surface
 Should not deliver an excess of calcium
 Should not favor calculus formation
 Should work at an acidic pH to stop demineralization during a carious
attack
 Should be able to work in xerostomic patients as saliva cannot effectively
stop the carious process
 Should be able to boost the remineralizing properties of saliva
 The novel materials should be able to show some benefits over fluoride.
 INDICATIONS
 Caries reduction in high-risk patients as an supplemental preventive therapy
 In patients with gastric reflux or other disorders to reduce dental erosion. •
 For reduction of decalcification in orthodontic patients
 Enamel repair in white-spot lesions
 Fluorosis or sensitive teeth before and after teeth whitening
 REMINERALISING AGENTS
Fluoridated Non Fluoridated
✓ Fluoride toothpaste  CPP-ACP
✓ TiF4  Bioactive Glass
✓ CPP-ACFP  Tricalcium Phosphate
 ACP Technology
 Self Assembling Peptide
 Dicalcium Phosphate Dihydrate
 Nanohydroxyapetite
 Sucrose free Polyol Gum •
 Biomimetically modified MTA
 Anti plaque agents
 Electric field induced
Remineralization
 Theobromine
 Arginine
 Oligopeptides
 Polydopamine
 Proanthocyanidin
 Fluorides

and restraint the

microbial
helps in development
remineralization, and metabolism
more corrosive
safe than
it promotes the hydroxyapatite
development of
Fluoride is fluorapatite,
known for its
anti-caries
effect
AVAILABILITY

 They are supplied in the form of dentifrices and rinses.

 Professionally, they are used in the form of varnishes, solutions, gels and fluoride
releasing restorative materials.
MECHANISMS OF ACTION OF FLUORIDE IN
CARIES REDUCTION
1. Increase enamel resistance or reduction in enamel solubility
2. Increased rate of post eruptive maturation
3. Remineralization of incipient lesions
4. Fluoride as inhibitor of demineralisation
5. Interference with plaque microbes
6. Modification in tooth morphology
Fluoride at optimal levels has a definite anticaries effect which is a boon to preventive
dentistry.
 MECHANISM OF ACTION

When enamel is exposed to ionic fluoride,

it may be taken up with the formation of either fluorhydroxyapatite or calcium fluoride.

Ca10(PO4)6(OH)2 + F– + H+→Ca10(PO4)6(OH)F + H2O

The fluorhydroxyapatite formed will be situated in the outermost layers of enamel and

form an integral part of the tissue that is only lost if the entire mineral is worn away or
dissolved entirely.
 'Non-acidic' type

 Neutral Fluoride solutions,

 Fluoride tablets,
 Duraphat,
 Elmex,
 which have sufficient Fluoride content to react with the outer enamel
 and produce sufficient Ca2+ ions by dissolution of the solid tooth structure
 so that CaF2 and some Fluorohydroxyapatite (FAP) is precipitated.
 ACIDIC TYPE

 acidulated phosphate fluoride solutions,

 Fluor Protector,
 some toothpastes and
 acidic mouth rinses.
 These produce Ca2+ by etching the enamel surface directly because of the
low pH and precipitate CaF2 and FAP on the surface.
A)Personally used Fluorides
 Fluoride Dentrifices and Mouthrinses

 Dentrifices contain 0.1% fluoride and uptake of this fluoride in etched enamel or in
incipient lesions enhances remineralization.
INDICATIONS:

 Fluoride mouthrinses are advised for school children over 5 years of age,
 person with high caries susceptibility
 patients with orthodontic and prosthetic appliance
FLUORIDE TOOTH PASTE

Regular brushing of teeth with a fluoride

containing toothpaste can reduce dental
caries incidence.

contain 500–1500 ppm fluoride either in

the sodium fluoride (NaF) form or in the
complex monofluorophosphate form.

when MFP meets the oral fluids and tissues

and when it diffuses into plaque.

The MFP molecule hydrolysis occurs and

is caused by phosphatases

Therefore, by using an adequately

fluoridated toothpaste , this assists
remineralization of any hard tooth tissues.
B)Professionally applied Fluorides
 Fluoride Solutions- The topical solutions of fluoride used are 2% sodium fluoride, 8%
stannous fluoride and 1.23% of acidulated phosphate fluoride solutions.
 Initially a prophylaxis is done followed by drying and isolation of each quadrant and
this 2% sodium fluoride is applied for 3-4 minutes.

 This procedure is called Knutson’s technique which is done at 3, 7, 10 and 13 years.

 Calcium fluoride reservoir is formed in this technique.

 8% SnF2 is applied for 2 minutes and when this solution reacts with enamel, tin
phosphate, calcium fluoride and tin-fluoride-phosphate are formed.

 1.23% of acidulated phosphate fluoride solutions leads to demineralization of enamel

and hence forms calcium fluoride and releases phosphate. Phosphate shifts the
equilibrium leading to formation of hydroxyapatite and fluorapatite.
Fluoride Releasing Restorative Material
 Glass ionomer cement releases fluoride which is found to be incorporated in enamel
cavity walls and bacteria inhibiting acid production .
 Further fluoride recharge ability of glass ionomer cement helps in long term inhibition
of caries.
 The recharging ability of this cement fully depends on the hydrogel layer over glass
filler.
 Certain studies reported a “burst” of fluoride release, with high early release for 1 to 2
days, followed by a rapid decline
 can be recharged with extrinsic fluoride in the form of fluoride solution, varnish,
fluoridated dentrifice or fluoride mouthrinses
 Compomers

 Compomers contain polyacid-modified monomers with fluoride-releasing

silicate glasses and are formulated without water.
 Compomers release fluoride by a mechanism similar to that of glass and
hybrid ionomers, but the amount of fluoride release and its duration are less
than those of glass and hybrid ionomers.
 Also, compomers do not recharge from fluoride treatments
 GIOMERS
 Giomer restoratives are a hybridization of glass ionomer and resin
composite.
 They have the fluoride-release and recharge properties of glass-ionomer
cements along with excellent esthetics, easy polishability, and strength of
resin composites.
 Yap et al found that while giomer released fluoride, it did not have an initial
“burst” type of release like glass ionomers.
 CPP-ACFP
 There is a synergism in remineralising
potential
CPP-ACP + F
MECHANISM:

CPPs enhances efficacy of fluoride as a remineralizing agent

by keeping fluoride ions in solution

by forming fluoroapetite.
 Jayarajan J et al (2011) conducted an in vitro study and found that
remineralization efficacy of
 CPP-ACFP containing paste (Tooth Mousse Plus) > CPP-ACP containing paste
(Tooth Mousse)
Llena C et al (2015) evaluated the effects of (CCP- ACP) and (CPP-ACFP) versus fluoride
varnish

on the remineralisation of enamel white spot lesions (WSLs)

over a 12-week follow-up period

in patients aged between 6 and 14 years and

the DIAGNOdent values were significantly less in CPP-ACFP group at 4 weeks.

Also, CPP-ACFP show no significant effect in pit and fissure caries but have a specific smooth
surface caries effect.
 TiF4 Technology

 Titanium ion readily hydrolyze H2O to expel proton (H+) and render the
solution of low pH value.

H2 O Ti (H+) + O2
 Titanium ion imparts oxygen a strong tendency to form titanium phosphate
complex.
 The bond thus formed is not easily substituted even at low pH (pH 1) by
protons (H+), which renders the altered tooth surface demineralization
resistant
Non fluoride remineralizing agents
 Why to go for nonfluoride strategies
1. Fluoride is highly effective on smooth-surface caries, but its effect is limited on pit
and fissure caries.

2. A high-fluoride strategy cannot be followed to avoid the potential for adverse

effects (e.g., fluorosis) due to overexposure to fluoride.

3. Toxicity of fluoride increases with inadequate nutrition

4. Although fluoride had a profound effect on the level of caries prevalence, it is far
from a complete cure.
5. The anti-fluoride lobby which is mounting pressure poses certain legal limitations to
the use of fluorides.
6. Certain countries do not have fluoridated products.
NON FLUORIDATED REMINERALSING AGENTS
 The following classification will be used for discussing nonfluoride remineralization
strategies.
According to the mode of action

Agents which
Those neutralizing
interact with tooth Anti-plaque agents
the bacterial acid.
enamel
Agents which
interact with tooth
enamel
Casein Phosphor Peptide - Amorphous
Calcium Phosphate (CPP-ACP)
 Casein, a bovine milk phosphor-protein and is a natural food component.
 interact with calcium and phosphate
 It was discovered by Prof. Reynolds at the School of Dental Science at the University
of Melbourne in Australia

CPP are
then
produced from
aggregated purified by
a tryptic digest
with calcium ultrafiltration
of the milk
phosphate and
protein casein,
when delivered in a mouthrinse

The CPP-ACP technology has

demonstrated

To significantly increase the levels of

calcium and phosphate ions

in supragingival plaque

and promote the remineralization of

enamel subsurface lesions
 Mechanism of action

Calcium phosphate is normally insoluble that is, forms a crystalline structure at neutral pH.

CPP keeps the calcium and phosphate in an amorphous, noncrystalline state

As CPP have the ability to bind and stabilize calcium and phosphate in solution, as well as to bind to dental plaque and
tooth enamel.

In this amorphous state, calcium and phosphate ions can enter the tooth enamel

CPP stabilize ACP, localize ACP in dental plaque, thereby maintaining a state of supersaturation with respect to tooth
enamel, reducing demineralization and enhancing remineralization

The CPPs have been shown to keep fluoride ions in solution, thereby enhancing the efficacy of the fluoride as a
remineralizing agent

The high-concentration of calcium and phosphate ions in dental plaque have been extensively researched and proven to
reduce the risk of enamel demineralization and promote remineralization of tooth enamel
CLINICAL APPLICATIONS
 Used for both primary and permanent teeth.
 Fluoride-free regular Tooth Mousse is a safe product to use in babies’
 teeth especially young children under 2 years of age with early childhood caries.
 Used for patients with special needs such as those with intellectual impairment,
developmental and physical disabilities, cerebral palsy, Down syndrome
 problems such as those undergoing radiation therapy.
 Used for high caries-risk patients in an attempt to remineralize early enamel
lesions, early childhood caries, stabilize carious lesions awaiting treatment and
root surface caries.
 Used in cases of molar incisor hypomineralization (MIH).
 This is done for remineralizing hypoplastic molars and
 remineralization of white spot lesions (enamel opacities and some cases of
mild Fluorosis).
 Used in patients with orthodontic appliances for the purpose of caries
prevention and prevention/remineralization of white spot lesions.
 Used to reduce dentinal sensitivity by occluding patent tubules.
 Used as a substitute for toothpaste in those allergic to commercial
toothpastes
Commercially available products
 Amorphous Calcium Phosphate
 The ACP technology was
developed by Dr. Ming S.
Tung.
 In 1999, ACP was
incorporated into
toothpaste called
Enamelon and later
reintroduced in 2004 as
Enamel Care toothpaste
COMMERCIALLY AVAILABLE PRODUCTS WITH ACP

 Enamel Care
 Mentadent Replenishing White
 Day White ACP
 Enamel Pro prophy paste
 NANOHYDROXYAPATITE

 Hydroxyapatite is the main constituent of the dental tissues representing in enamel and
dentine the 95wt% and 75wt%, respectively.

 Poorly crystalline HA nanocrystals, have

advantages Disadvantages
• Has excellent biological properties of bioresorption properties under
HA, physiological conditions.
• such as nontoxicity and
• lack of inflammatory and immunizer
responses
 Bioresorption can be modulated by modifying its degree of crystallinity,

 achieved by the implementation of innovative synthesis with a nanosize crystals

control

 A concentration of 10% nano-hydroxyapatite (nHA) is considered to be optimal for

remineralization of early enamel caries.

 Also nHA has the potential to remineralize erosive enamel lesions caused by exposure
to soft beer and other aerated beverages.
 Toothpastes containing n-HA revealed higher remineralizing effects compared to
amine fluoride toothpastes with bovine dentine.

 An elevated Ca concentration in the remineralizing solution was also observed after a

single treatment with the nHA dentifrice
 PROENAMEL

 Despite its name, Pronamel™ (GlaxoSmithKline, Middlesex, UK) is not considered a

remineralizing agent per se, and it does not contain any calcium compounds.

 The results of studies conducted show that pronamel reduces enamel erosion from
acidic challenges from diet, fruit juices.
 After treatment with the demineralizing solution followed by Pronamel, both
interprismatic and prismatic enamel structures still appear evident
 Calcium carbonate carrier (SensiStat)

 The SensiStat technology was developed by Dr. Israel Kleinberg of New York.

 The technology was first incorporated into Ortek’s Proclude desensitizing Prophy
Paste and later in Denclude.

 Commercially available sensistat products

 • ProClude
 • DenClude
 A prime reaction is that the highly soluble arginine bicarbonate component of
SensiStat surrounds, or is surrounded by particles of the poorly soluble calcium
carbonate component.
 Because of the adhesive properties of the composition forms a paste-like plug that
not only fills the open tubules but also adheres to the dentinal tubule walls.
 So, reacts with the calcium and chemically contiguous with the
It is alkaline in nature phosphate ions of the dentinal Forms the plug dentinal walls and, therefore,
fluid more secure.

 Subsequent testing of the plug by exposure to strong external acids has confirmed that it is firm. This composition
has received US FDA approval
 To conclude, SensiStat can be used to treat early surface demineralizations, and halt development to frank caries
that requires restoration.
Self-Assembling Peptide

 Recent developments in research have revealed the role of treatment with

peptide where it proved a combined effect of increased mineral gain and
inhibition of mineral loss from the tooth.
 Single application of P11-4 is beneficial in the treatment of early caries
lesions.
MECHANISM OF ACTION

under defined environmental conditions

β sheet forming peptides P11-4 self-assembles themselves to form

three-dimensional scaffolds

The anionic groups of the P11-4 side chains attract Ca++ ions,
inducing the precipitation of hydroxyapatite in situ

nucleate the hydroxyapatite de novo

facilitates mineralized tissue regeneration,

thus mimicking the action of enamel matrix proteins during tooth

development.
 TRICALCIUM PHOSPHATE

which results in
It fuses beta
a enhance the
created with a TCP and
is a new hybrid “functionalized” fluoride
milling sodium lauryl
material calcium and a remineralization
technique sulfate or
“free” efficacy.
fumaric acid
phosphate
Moistened by saliva
 Trimetaphosphate ion

It involves adsorption of the agent to the enamel surface,

Creates barrier coating that is effective in preventing or retarding reactions of the crystal surface
with its fluid environment, and
TMP assists the diffusion of calcium ions to the inner of enamel
or reduced their loss to the solutions
hence reducing demineralization
during acid challenge.
 Sucrose-free polyol gum

 Xylitol is a non- cariogenic five -carbon sugar alcohol

 found naturally in plants
 used as a substitute for sugar.
 It is believed to be a “tooth-friendly”
 Xylitol coating inhibits early reaction and results in sustained remineralizing
ions release.
 It act as a carrier for calcium required for remineralization.
 When exposed to saliva, xylitol dissolves. As a result, phosphate and calcium
ions gets free which form protective fluorapatite on the teeth
 Xylitol can be best used soon after eating and clearing the mouth by
swishing with water.
 Grape Seed Extract

contains proanthocyanidin

is an antioxidant and which interacts

microbial cell membrane proteins, and
lipids resulting in lysis of cell membrane
thereby resulting in arrest of
root caries.

inhibits the
glucosyltransferase enzyme
produced by S mutans

resulting in inhibition of Dental Caries.

potent substitute for fluorides for the

prevention of root caries in elderly
patients.
MISWAK
 Salvadora persica
 contains nearly 1.0 μg/g of total fluoride and was found to release
significant amounts of calcium and phosphorus into water (Char et al., 1987
).
 contains benzylisothiocyanate (BITC) has exhibited broad-spectrum
bactericidal activity (Pulverer, 1969) and was found to inhibit the growth and
acid production  of Streptococcus mutans
 Tannins were found to inhibit the action of glucosyltransferase, thereby
reducing plaque
 The pungent taste and chewing effects of miswak may increase saliva
secretion in the mouth, thereby increasing its buffering capacity  thereby
raising the plaque pH.
 All these prevent demineralization and promote remineralization.
Commercially available herbal containing
dentrifices
 Bioactive Glass

 Bioglass was invented by Dr. Larry Hench in1960s.

 The NovaMin Technology was created by Dr. Len Litkowski and Dr. Gary
Hack
 a very fine Bioglass 45S5 particulate called NovaMin is a trade name for
bioactive glass
FUNCTIONS:
 It acts as a biomimetic mineralizer matching the body’s own mineralizing
traits
 also affecting cell signals in a way that benefits the restoration of tissue
structure and function
 has antimicrobial activity towards Steptococous mutans and Streptococcus
sanguis.
 aids in remineralization of tooth structure especially in patients with systemic
problems
MECHANISM OF ACTION

interacts with saliva and

discharges sodium, calcium, and

phosphorous particles into the spit

these are accessible for

remineralization of the tooth
surface.
They discharge particles
and change into HCA for
as long as about
fourteen days.

At last, these particles will totally

change into HCA.
ADVANTAGES
 Caries can also result from inadequate saliva, without which fluoride is of
limited value.
 Thus, individuals who experience reduced calcium, phosphate and fluoride
ions caused by hyposalivation can benefit from the use of bioactive glass.
Commercially available products
 DenShield Conditioner with NovaMin,
 NuCare-Prophylaxis Paste with NovaMin,
 Oravive,
 NuCare-Root NovaMin
 SootheRx
 DICALCIUM PHOSPHATE DIHYDRATE

Incorporation of dicalcium phosphate dihydrate in a dentifrice

upsurges the levels of free calcium ions in plaque fluid and

they remain elevated for up to 12 hours after brushing in comparison to

conventional dentifrices.

The interaction of DCPD and fluoride forming fluorapatite may provide a

potentially encouraging remedy for remineralization of caries lesions in vivo.
 REMIN PRO
It is a water based cream containing calcium, phosphate in the hydroxyapatite form.

In addition, fluoride and xylitol have also been included in this product.

Hydroxyapatite fills the superficial enamel lesions and tiniest irregularities that arise from erosion.

Fluoride gets converted to fluorapatite when it comes in contact with saliva; thus, strengthens the tooth and renders it more
resistant to acid attacks.

Xylitol reduces the harmful effects of bacteria and their metabolic product lactic acid.

Usage of Remin Pro after bleaching showed a considerable increase in microhardness, which was comparable with GC tooth
mousse.

It is credited to the presence of 1450ppm fluoride, which is 61% higher than GC tooth mousse.
 Biomimetically Modified MTA

 For remineralization of dentin, biomimetic analogs in modified MTA provides

a potential delivery system.
 It widens MTA applications in dentistry as it release biomimetic analogs from
set MTA.
 When availability is compromised, polyphosphate in the MTA serve as a
supplementary phosphate source.
THEOBROMINE
 Member of the xanthine family which is seen in cocoa (240 mg/cup) and
chocolate (1.89%)
 enhance crystalline growth of the enamel.
 Amaechi et al evaluated the remineralisation potential of sodium fluoride
dentifrice and theobromine and a significantly higher amount of
mineralization was seen with theobromine and fluoride toothpaste relative to
artificial saliva.
 Grace Syafira et al. have shown an increased enamel microhardness after
treatment with theobromine on the enamel surface.
 Meanwhile, Nasution AI noticed the increase in enamel surface hardness by
the application of fluoride is higher than the theobromine.
Electric Field-induced Remineralization

This technique was introduced by Wu (Reminova Ltd )

for remineralization of completely demineralized dentin collagen matrix and

to reduce the mineralization time

relies on the use of an electric current to reverse tooth decay by boosting remineralization.

The use of tiny electric current of few microamperes that cannot be felt by the patient pushes
the minerals into the tooth to repair the clean defect.

This process requires no injection, no drilling of tooth, and no filling materials and triggers the
remineralization from the deeper portion of the lesion.
 OZONE

 Ozone is derived from Greek word “ozein“.

 It is a gas allotrope discovered by Christian Friedrich Schönbeinin in 1840.
 Ozone is a chemical compound consisting of three oxygen atoms (O3 ,
triatomic oxygen).
 Ozone therapy has proven to be effective with a wide range of dental
applications, including prosthodontics, endodontics, periodontics, surgical
procedures, and preventive dentistry.
FUNCTIONS:
 for sterilization of cavities, root canals, periodontal pockets, and herpetic
lesions.
 stimulate remineralization of incipient caries
 Ozone can kill bacteria in carious lesions,
 help in oxidizing organic material within the carious dentin,
 helps in opening of channels inside dentin
 leading to penetration of calcium and phosphate ions and remineralisation.
 Ozone is a toxic gas especially for pulmonary tract.
 Therefore for its use in medicine one must avoid its toxicity with the help of
special instruments like precise ozone generator equipped with well-
standardised photometer, appropriate monitor, ozone destructor and an
emergency air depurator
 Those neutralising bacterial acids

 Other strategies to combat demineralization include neutralizing bacterial acid using

calcium carbonate as plaque pH buffering effect and sodium bicarbonate to provide
an alkaline oral environment.
 Alternatively, calcium containing agents like calcium lactate, calcium
glycerophosphate, and calcium phytate can be used.
 They act by increasing plaque calcium and phosphate levels
 Also, toothpastes containing chlorophyll, ammoniated toothpaste, and anti-enzyme
pastes can be used
Antiplaque agents
Anti-microbials and antibiotics-
 A variety of antibiotics and antimicrobials are used to combat dental plaque.

 Many types of mouthrinse active ingredients have been evaluated for their plaque-
reducing effectiveness and ability to reduce mutans streptococci, including
chlorhexidine, essential oils, triclosan, cetylpyridinium chloride, sanquinarin, sodium
dodecyl sulfate, and various metal ions (tin, zinc, copper)
 Chlorhexidine applied as a rinse partially reduces some bacteria but not others that are
hiding within the biofilm

 Xylitol delivered by gum or lozenge appears to be effective clinically in reducing

cariogenic bacteria and caries levels

 but novel systems that deliver therapeutic amounts when needed would be a major
advance, especially for young children
 Laser induced enamel remineralization

 For caries prevention, in order to alter the composition or solubility of dental

hard tissues, the laser light must be strongly absorbed and converted
efficiently to heat without damage to underlying or surrounding tissues
 specific wavelengths must be chosen where absorption is high in regions
which correspond to specific components in dental hard tissues, such as
hydroxyapatite and water which are the main targets of enamel
remineralization.
 Many laser systems like CO2, Er:YAG, Er,Cr:YSGG, Nd:YAG and diodes have
shown promising results in enamel remineralization
high-power lasers Low Level Lasers
CO2 (Diodes with 660nm-980nm
erbium lasers (Er:YAG) wavelengths)
are effective in white spot lesion
prevention
MECHANISM OF ACTION:
 absorb water from the
hydroxyapatite of tooth tissues  inhibition of enamel diffusion through
 can modify the crystalline the modification of organic matrix
structure,  organic blocking’
 High-energy laser treatment has  preserves and modifies the organic
been used to melt the enamel and matrix to obliterate the diffusion
to ‘seal’ the surface for caries channels in enamel
prevention. ADVANTAGES
DISADVANTAGES:  relatively inexpensive,
 potentially damage the gingival or  small, and
pulpal tissues  portable
 fine enamel cracks, which were
starting points for acid attack
COLD PLASMA
 Cold plasmas are gaseous media generated at low pressure
 In contrast to laser beams, which propagate linearly and are prone to being
scattered, cold plasma can penetrate into irregular cavities and fissures.
Moreover, it kills only pathogens in bacterial plaque without damaging the oral
tissues

MECHANISM OF ACTION:
 modification of surface properties such as the electrochemical charge
 amount of oxidation, as well as attachment of surface-bound chemical groups.
 such as hardness, resistance to physical abrasion, wettability, and affinity
towards specific molecules
 EMDOGAIN

 EMDgel is a commercially available mixture of EMD dissolved in PGA carrier.

 It was first used in 1999 by the Swedish Company Biora
 EMDgel, may promote remineralisation of initial enamel carious lesions,
 initiating crystal nucleation, guiding and supporting crystal growth, protecting
the mineral phase, binding mineral ions, and modulating growth rate
 EMDgel as a whole did not exert a clear remineralisation effect, in contrast to
the widely used anticaries agent fluoride
POLY(AMIDO AMINE)
 Dentin is composed of HA, organic matrix, and water.
 Collagen fibrils are the main component of the demineralized dentin.
 However, the nucleation rate of collagen fibrils is far too slow without the use of
nucleation template materials
 Non-collagenous proteins (NCPs), although composing of only about 3% of the organic
components of dentin, play a vital role in the modulation of the biomineralization process
 NCPs are regarded as the nucleation templates within the collagen fibrils, which can
control the hierarchical growth of HA
 In mature dentin, however, NCPs lose the ability to initialize remineralization
 amelogenin is a wellknown example, act as nucleation templates in the biomineralization
process of enamel
 PAMAM are highly branched polymers with internal cavities and a large
number of reactive terminal groups.
 Several different generations of PAMAM with different structures were
synthesized.
 The first and second generations of PAMAM are linear molecules,
 while the third and higher generations are sphere molecules with a larger
number of functional groups
MECHANISM OF ACTION
 PAMAM–COOH acted as the organic nucleation template to induce biomimetic
new-grown crystals on the demineralized enamel.
 PAMAM–COOH absorbed Ca and P ions within collagen fibrils to induce
intrafibrillar remineralization.
 PAMAM–PO3H2 was absorbed on demineralized enamel surface tightly and
produced an enamel prism-like structure,
 PAMAM–PO3H2 bound tightly to dentin collagen fibrils, and induced effective
regeneration of demineralized dentin
 In addition, PAMAM–NH2 induced the regeneration of minerals on both collagen
fibril surface and demineralized dentin surface

 SMART COMPOSITES
 These are light-activated, nano-filled restorative materials.
 Amorphous calcium phosphate is used as a filler phase in bioactive polymeric
composites.
 Such composites release calcium, fluoride, and hydroxyl ions when intraoral pH
values drop below the critical pH of 5.5 and
 prevents the demineralization of the tooth surface and also aids in
remineralization.
 These ions are then deposited into tooth structures as apatitic mineral, which is
similar to the hydroxyapatite (HAP) found naturally in teeth and bone
Probiotic bacteria

 Examples of probiotics that have the ability to confer oral health benefits for the host include Lactobacillus
(eg, salvarius,reuteri, and rhamnosus) and Bifidobacterium that are part of normal oral flora .
 The use of probiotic products found a potential use as alternative strategy for the prevention of enamel
demineralization
MECHANISM OF ACTION:

biotherapy for prevention or treatment of dental caries and periodontal diseases

by reducing the number of pathogenic bacteria (S. mutans) or

inhibiting the expression of S. mutans virulence genes,

for example, GtfB and LuxS140,145 and therefore alter or reduce biofilm formation
Dispensing Methods
 Remineralizing agents can be incorporated into different products for
application.
 Commonly used vehicles are restorative materials, pit-and-fissure sealants,
dentifrices, chewing gums, and rinses.
 Clinical applications

White spot lesions:

 DEFINITION:WSL has been defined as “subsurface enamel porosity from
carious demineralization” that presents itself as “a milky white opacity . . .
when located on smooth surfaces.”
Treatment options:
 xylitol gum
 casein derivates
 fluoride toothpastes, gels, varnishes, and mouth rinses; antimicrobials;
Experiences of oral health: before, during and after becoming a regular user of GC
Tooth Mousse Plus® Alexandra Sbaraini* , Geofrey G. Adams and Eric C. Reynolds

 AIM:The aim of this study was to identify how participants oral health status changed after
introducing TMP into their oral hygiene routine.
 Results: Participants described their experiences of oral health and disease, before, during and after
introducing TMP into their daily oral hygiene routine.

 Conclusions: Participants valued having a comfortable mouth with strong teeth, which did not
require repeated restorations. Seeing concrete results in their mouths and experiencing a more
comfortable mouth boosted adherence to daily applications of TMP, which was maintained over
time
Comparative Evaluation of Combined Remineralization
Agents on Demineralized Tooth Surface A Aras, S Celenk1 ,
MS Dogan, E Bardakci
 Objectives: The aim of this in vitro study was to evaluate the effects of
casein phosphopeptides (CPP)‑ACPF, NovaMin+ fluoride‑containing
toothpaste and Xylitol+ fluoride containing cream on demineralized areas on
the enamel surface.
 Conclusions: Remineralization was provided in all treated groups, according
to the data obtained from all tests.
 NovaMin was more effective in increasing acid resistance.
 It was also found that all three experimental groups were effective in
increasing the surface hardness,
 but CPP‑ACPF and NovaMin are more effective than Xylitol.
 Enamel remineralization assessment after treatment
with three different remineralizing agents using surface
microhardness: An in vitro study Shishir Shetty, Mithra
N Hegde, Thimmaiah P Bopanna

 Aim: The aim of this study is to evaluate the enamel remineralization after
treatment with three different remineralizing agents using surface microhardness
assessment.

 The groups treated with remineralizing agents were subjected to pH cycling over
a period of 28 days. This was followed with assessment of surface
microhardness (Micro Vickers Hardness tester, Matsuzawa Co., Ltd, Toshima,
Japan).
 Results: There was an improved enamel remineralization in the group,
remineralized using CPP-ACPF in comparison with the other groups.
 Conclusion: Casein phosphopeptide with fluoride is a promising material for
remineralization of enamel subsurface lesions
 CONCLUSION

 Evidence suggests that initial noncavitated lesions can be remineralized using

appropriate technologies, both fluoride and nonfluoride based

 Saliva plays an important role in the remineralization. Also, it is important that the
control of caries be dealt with biofilm control.

 The nonfluoride remineralization strategies will be of benefit to many.

 Because of changes in dietary habits, lifestyle, and longer life expectancy, there is an
increasing prevalence of enamel and dentin erosion, dental caries and other factors
which affect the health of dental tissues.

 With these nontoxic alternative remineralization strategies, we would be able to re-

establish the health of oral tissues without being under the risk of fluoride toxicity if
ingested at high levels, in particular in children
 REFERENCES
 The Chemistry of Caries: Remineralization and Demineralization Events with Direct Clinical Relevance
Carlos Gonzalez-Cabezas, DDS, MSD, PhD
 Laser induced enamel remineralization: A systematic review Chandrashekar M Yavagal, Viplavi V Chavan
and Puja C Yavagal
 Remineralizing Agent -Then and Now -An Update Naveena Preethi P* , Nagarathana C and Sakunthala
BK
 Joshi SR, Gowri Pendyala D, Mopagar Viddyasagar D, Padmawar N, Nara A, Joshi P. Remineralizing
agents in dentistry: A review.
 Aras A, Celenk S, Dogan MS, Bardakci E. Comparative evaluation of combined remineralization agents
on demineralized tooth surface. Niger J Clin Pract 2019;22:1546-52.
 Effect of Three Different Pastes on Remineralization of Initial Enamel Lesion: An in Vitro Study Vyavhare
S*/ Sharma DS**/ Kulkarni VK
 Dental remineralization via poly(amido amine) and restorative materials containing calcium phosphate
nanoparticles Kunneng Liang1,2, Suping Wang2,3, Siying Tao1 , Shimeng Xiao1,2, Han Zhou2 , Ping
Wang2 , Lei Cheng1,2, Xuedong Zhou1 , Michael D. Weir2 , Thomas W. Oates2 , Jiyao Li1 and Hockin
H. K. Xu
 The Clinical Applications of Tooth MousseTM and other CPP-ACP Products in
Caries Prevention: Evidence-Based Recommendations
 White Spot Lesions: Formation, Prevention, and Treatment Samir E. Bishara
and Adam W. Ostby
 Dental caries - A complete changeover (Part I)Carounanidy Usha and
Sathyanarayanan R
 Arjan Vissink, DDS, PhD, Frederik Karst Lucien Spijkervet, DDS, PhD, Arie Van
Nieuw Amerongen, PhD Aging and saliva: A review of the literature
 State of the Art Enamel Remineralization Systems: The Next Frontier in Caries
Management Nebu Philip School of Dentistry, University of Queensland,
Brisbane, QLD, Australia