NOVEL STRATEGIES
TO IMPROVE
STABILIZATION OF
ADHESIVE INTERFACES
Presented by: Pansai Ashraf
Supervised by: prof. Amal Ezz-Eldin
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√ What is hybrid layer
√ Causes of hybrid layer degradation
√ Novel strategies to improve stabilization of adhesive
interfaces:
Outline:
1- Changing the monomer structure
2-MMPs Inhibitors + Peptide engineering.
3- Enhancing the monomer degree of conversion
4-Novel resin formulation
5 -Adhesives with remineralization functions
6-Antibacterial Bond System
7-Strategically linking biology & engineering
8- Removal of Proteoglycans hydrogel in interfibrillar spaces
9- Ethanol wet bonding concept
10- Biomodification of Dentin
11- Clinical technique to improve adhesive stability
12-Nano-adhesive releasing therapeutic ions
13- Self healing adhesives
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Longevity of composite
restorations depends on
adhesion between tooth
substrate and restorative
materials.
….As a result, Failure in
adhesion leads to restoration
failure.
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Adhesion of composite restorations occurs as a
result of hybrid layer formation …
So,
What is hybrid layer?
Hybrid means→ composed of different materials or phases.
* It is a layer of dentin penetrated by a bonding agent forming resin tags.
(dentin collagen + bonding agent )
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1- Degradation of Adhesive-Dentin Interface
Causes of
hybrid layer
degradation
1.1.Proteolytic Enzymes
*Matrix metalloproteinases especially MMP-8, and cysteine cathepsins attack type
I collagen (the most abundant type of dentin collagen).
*These enzymes are activated by:
√ proteinases, chemical agents, low pH, heat treatment and mechanical stress .
√ Acid-etchants and bacterial acids.
√ Incomplete resin infiltration
NB: Exposed dentin collagen express binding sites for MMPs and cathepsins.
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1.2. Chemical/Biochemical Interactions
pulpal pressure results in: pumping dentin fluid through dentinal tubules
Causes of
hybrid layer
degradation
→hydrolysis of hydrophilic resins→ reducing sealing ability & bond durability.
methacrylate adhesives contain ester bonds subjected to chemical and/or
enzymatic hydrolysis.
Human saliva contains cholesterol esterase →degrade dimethacrylates.
1.3. Mechanical Loading
Masticatory forces can affect the bonding interface.
Masticatory forces → tooth bending → gap formation → microleakage and
recurrent caries.
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2. Microleakage
It occurs due to:
2.1 polymerization shrinkage:
(contraction stresses  bond strength) → marginal gaps → microleakage → recurrent
caries.
Causes of
hybrid layer
degradation 2.2 Bacterial enzymes:
Ex:
Collagenases →increase nano-leakage
Lactic acid →activate MMPs
3. Hydrolysis of resin by water sorption
Adhesives with hydrophilic monomers like HEMA (Hydroxy ethyl-methacrylate:
✓ Enhances the wettability and impregnation of adhesives to dentin.
✓ Increase hybrid layer permeability →increase water sorption→ separations
between hydrophilic and hydrophobic polymerized resins →bond degradation
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Causes of 4.Incomplete resin infiltration
hybrid layer
leaves unprotected collagen and porosities in the hybrid layer.
degradation
Results in :
Incomplete water removal from interfibrillar spaces (between collagen fibers) →water
accumulation → hydrolysis → decreased bond strength & increased nano leakage.
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Consequences of bonding failure:
microleakage
postoperative
sensitivity
staining
recurrent
caries
Restoration failure
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HYBRIDLAYER
STABILIZATION
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1- Changing monomer
structure
The hydrophobicity of the monomers can be
increased by incorporating:
✓ Urethane group
✓ Branched methacrylate linkage
✓ Ethoxylated BisGMA
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2- MMPs inhibitors
NB:
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MMPs
inhibitors
1- chlorhexidine :
Cationic-anionic reaction
☺has a +ve charge.
☺electrostatically binds to –ve charged catalytic sites of MMPs.
☺blocks active sites.
☺Chelates with zinc or calcium in catalytic domain.
loss of catalytic activity of MMPs
with better bond durability☺
2- Alcohols:
⁎alcohols can inhibit MMPs by forming a covalent bond between MMP’s catalytic zinc and alcohol’s
oxygen atom.
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MMPs
inhibitors
3-Protein cross-linking:
Cross-linker function
1-produce conformational changes in MMPs 3D structure
2-hinder molecular mobility → interfere with enzyme activity.
3-Stabilize hybrid layer → improve bond strength.
Ex: Glutaraldehyde, Hesperidin, Riboflavin, Grape seed extract & tannic acid.
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Glutaraldehyde
*cross-linking by
covalent bonds
between amino
groups of proteins
and the aldehyde
groups of
glutaraldehyde.
Hesperidin
Riboflavin
*natural photo initiator
(extracted from citrus
fruits) → increase
mechanical properties of
hybrid layer &
immediate bond
strength of self-etching
adhesive
*cross-linking agent
used with dental blue
light
Grape seed extract
*(GSE) is a natural
cross-linker.
*better bond stability.
*Inhibit MMPs
activity
*biocompatible
and production.
*5% glutaraldehyde
for 1 min after acid
etching →better bond
stability.
* disadvantage: toxic
at high concentrations
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MMPs
inhibitors
4-Galardin:
1-Synthetic MMP inhibitor.
2-Attack the active sites and
chelate the zinc ion in MMP.
3-Reduce nano-leakage.
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MMPs
inhibitors
5-Peptide engineering :
✓ Strong inhibition of MMP-8 by small metal binding
peptide (metal abstraction peptide MAP).
✓ MAP is a small peptide capable of robbing transition
metal ions, ex: Zn from chelators.
✓ MAP is grafted into amine-containing polymers.
✓ MAP bind to zinc at the catalytic domain of MMP-8.
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3- Enhancing the monomer degree of conversion
Monomer degree of conversion can be improved by:
1-Water-soluble photo-initiators → resist cleavage by esterase.
2-Photo-initiators that are compatible with the hydrophobic and hydrophilic parts of adhesive.
3-Increasing the light-curing time.
EX: sulfinates or sulfonates are added to SEA:
Why?
CQ is adversely affected by presence of acidic monomers in SEA
How do they act?
✓ promote the photopolymerization of self etch adhesive SEAs → improve the DC & μTBS.
✓ promote polymerization by scavenging oxygen (O2 is an inhibitor).
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4- Novel resin formulation
Modified formulations:
✓ Silyl-functionalized BisGMA.
✓ Resin containing γ-methacryloxyproyl trimethoxysilane (MPS).
(BisGMA) is the most common
crosslinking monomer in dental
adhesives…
1- Silyl-functionalized BisGMA
Ex: methoxysilyl-functionalized BisGMA.
➔ Drawbacks: high susceptibility to
hydrolysis → affect durability.
silyl-BisGMA provide:
✓ Higher crosslinking compared to BisGMA/HEMA .
✓ Higher hydrolysis resistance.
Leading to….
➢ Decreased degradation
➢ Decreased leached HEMA by 90%
➢ Retain mechanical properties
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Novel resin formulation
2- Resin containing γ-methacryloxyproyl trimethoxysilane (MPS)
→ Has intrinsic self-strengthening properties
Basis:
photoacid-induced sol-gel reaction + free
radical photo-polymerization reaction of methacrylate
Mechanism:
➢ light curing → free radical polymerization of methacrylate monomers
(HEMA, BisGMA, and MPS).
➢ After that, photoacid-induced sol-gel reaction continues ″without light ″
➢ After 48 h, 65% of silyl groups undergo hydrolysis
➢ After exposure to water or lactic acid→ the hydrolysis continues, and new
crosslinked points are formed.
*Also, the silanol groups react with the hydroxyl groups of
HEMA or BisGMA forming covalent bonds (Si−O−C).
Example for commercially available adhesive :
Clearfil Porcelain Bond Activator → can be mixed with the
adhesive
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5- Adhesives with remineralization functions
✓ NB: Protease and cariogenic bacteria cause demineralization of dentin in
hybrid layer..
 Remineralizing adhesives action mechanism:
✓ Promote microcracks healing and acids neutralization by raising the pH.
✓ Provide alkaline ions like Ca and P → acids neutralization .
✓ Promote the epitaxial growth of the remaining HA crystals in partially demineralized dentin.
Example for commercially available adhesive :
fluoride-releasing adhesives (OptiBond Solo and Reactmer Bond)
This can be achieved by addition of bioactive glass (BAG), calcium phosphate , and HA.
✓ Source of Ca and P ions.
✓ Allow deposition of calcium phosphate on crystals surfaces.
✓ Protect collagen fibrils → MMPs is fossilized by the crystal growth.
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Bioactive glass
☺ anti-microbial activity→
increase the pH by release of
alkaline ions: Na+ or K+
exchanged with H+ or H3O+
ions.
☺ Inhibit MMP due to
alkaline ions (MMP act at pH 7).
calcium phosphate
☺ α tricalcium phosphate (-TCP)
nanofiller improve bond
strengths.
Hydroxyapatite
☺ 7 wt% nano HA improve
the immediate micro-tensile
bond strength.
☺ amorphous calcium
Phosphate nanoparticles (NACP)
up to 40 wt% provide Ca and P
ion without affecting bond
strength.
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6-Antibacterial Bond System
Bacteria
secrete enzymes
demineralization
microleakage and recurrent caries
antibacterial
primer
√ Bacteriostatic effect
√ Inhibit recurrent caries at adhesive interface
Antibacterial
agents
antibacterial
Bonding agent
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Examples:
1- Silver nanoparticles (NAg):
Ag ion role:
a) inhibit bacterial enzymes .
b) alter bacterial DNA leading to cell death.
2-Chitosan
-Antibacterial agent that can be incorporated in dental adhesives
-But: bond strength decreases as chitosan content increases .
Ex: methacrylate-modified chitosan primer , possess both hydrophilic and hydrophobic features, and can
interact with the restorative material and tooth structure.
→ A higher value of bond strength was recorded at chitosan 0.2 % compared to 2.5 %.*
3- Quaternary Ammonium Salts (QAS) :
√ Positively-charged → bind to negatively-charged bacteria cell → alter membrane permeability
→ cytoplasmic leakage → bacterial death.
* Effect of chitosan nanoparticles on microtensile bond strength of resin composite to dentin: An in vitro study.2020.
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Examples:
4- Chlorohexidine (CHX):
√Antibacterial agent even at low concentration (0.05–0.2%).
√ Inhibit bacterial proteolytic enzymes.
√ Electrostatically binds to demineralized dentin.
√ Can be added to the primer or bond.
5- Doxycycline (DOX):
√ A tetracycline derivative
√ Inhibit cariogenic bacteria such as S. mutans & Lactobacillus
Ex:
- Doxycycline (DOX)-encapsulated nanotubes incorporated into the dentin bonding agent
Provide sustained release of DOX → inhibit MMPs & cariogenic bacteria.
Evaluation of the micro-mechanical strength of resin bonded-dentin interfaces submitted to short-term degradation strategies. 2012.
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• Example for commercially
available adhesive:
→ G-ænial Bond
*Generally, Self-etch adhesives showed
higher antibacterial activity than total etch
adhesives.
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7- Strategically linking biology & engineering
1- Proton Sponge Adhesives:
✓ Recurrent caries results from cariogenic plaque at restoration margins.
✓ Cariogenic plaque→ (pH < 5) →acid demineralization & enzymatic degradation
of methacrylate ester groups in adhesives.
✓ degradation of methacrylate ester groups produces carboxylic acids, → the same
functional group in lactic acid → induce caries.
✓ Cariogenic plaque at restoration margin can be reduced by neutralizing the
acidic microenvironment.
This can be done by :
Incorporating a neutralizing agent→ act as a neutralizing proton sponge.
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Strategically linking biology & engineering
Incorporating amine-containing monomers:
Ex: 2-(dimethylamino) ethyl methacrylate (DMAEMA) → buffering effect .
But ….
Drawback → leaching of amine-containing cytotoxic species.
So… the alternative strategy involves the use of biomolecules.
2-Modulating pH with biomolecules:
❖ Lysine- based dental adhesives
Essential amino acid
Act as a weak base
Antibacterial properties
→Buffer the micro-environment without leaching amine-containing cytotoxic species.
❖ arginine-based dental adhesives
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8- Removal of Proteoglycans hydrogel in interfibrillar
spaces
▪ Dentin → collagen + glycosaminoglycan / proteoglycan.
▪ GAGs /proteoglycans → bind to collagen → prevent adhesive
infiltration into interfibrillar spaces → accumulation of water in HL.
▪ Moreover, GAGs (ex: Chondroitin sulfate) → highly polar and -ve
charged → high tendency to attract water into interfibrillar spaces.
▪ Water → hydrolysis & degradation .
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Removal of Proteoglycans hydrogel in interfibrillar spaces
Removal of proteoglycans by enzymatic treatment:
Examples:
✓ Chondrotiniase
✓ Trypsin
→ It was found that, removal of PGs (chondrotin sulphate) leads to:
√ Change surface energy
√ help in water displacement
√ improved resin infiltration
√ improve TBS
√ reduce nano-leakage
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9- Ethanol wet bonding
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9- Ethanol wet bonding
Problems of water wet bonding ???
Water tree formation …
Acts as a semi-permeable membrane → osmotic effect
and fluid movement → trapped moisture → ↓ composite curing
→ hydrolysis and degradation at interface.
this can be overcome by:
Ethanol wet bonding
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Ethanol wet bonding
✓ This technique replaced water wet technique.
✓ It is used to dehydrate the exposed collagen without collapsing.
✓ The water in DT is replaced by ethanol.
 In addition;
✓ Ethanol dissolves hydrophobic resin such as TEGDMA
(Tri Ethyl Glycidyl Di Methacrylate) making them more hydrophilic.
✓ When HEMA is used as a primer; HEMA/alcohol, it shows better infiltration
compared to HEMA/water.
-------------------------------------------------------------------------------------------------
Advantages
1-Better dentin wettability.
2-Better bond penetration and sealing with DT.
3-Better bond durability.
Disadvantages
1-Technique sensitive
2-Additional steps & more time
Etch with 37%
phosphoric
acid (15 sec.)
Rinse and
leave moist
with water
Add 99.5%
ethanol on
moist surface
Add bonding
agent before
ethanol
evaporation
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Ayar et.al 2014 found that;
Ethanol-wet-bonding increase
the Microtensile bond strength
from 17.4 MPa to 28.7 Mpa
compared to Water wet bonding.
Effect of ethanol-wet-bonding technique on resin–enamel bonds. Journal of Dental Sciences. 2014.
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10-Biomodification of Dentin
Dentin biomodification improves mechanical properties through nonenzymatic
collagen cross-linking.
(1) Physical Agents.
Using photo-oxidative techniques.
By the action of (UV) light requires → the presence of oxygen free radical (reactive & unstable).
Ex:
Vitamin B2 (riboflavin)
✓ Source of oxygen free radicals,
✓ Activated by UV light → induce covalent bonds formation between the amino group of
✓ glycine of collagen and the carbonyl groups of hydroxyproline of side chains
→ cross-linking of collagen
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Biomodification of Dentin
(2) Nonspecific Synthetic Cross-Linking Agents :
Cross-linking agents
√ Stabilizes the structure.
√ Increase resistance to enzymatic degradation.
Ex:
1) Glutaraldehyde 5%
2) Carbodiimide (EDC) 0.1; 0.3, 0.5 M: Less cytotoxic→ activation → reacts with the
amino groups in collagen→ cross linking
⁎Limitation: release of urea → delay cross-linking (1h) → limit the clinical use.
(3) Biomimetic Remineralization:
The use of amorphous calcium phosphate nanoprecursors for biomineralization of dentin.
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Biomodification of Dentin
(4) Natural Cross-Linking agent.
Antioxidant materials
√ Promote cross-linking with collagen
√ Inhibit MMPs.
Ex:
Grape seeds derivative (oligomeric proanthocyanidin).
limitations:
1-Long application times (10 min to 1h) not clinically applicable.
2-Reduced degree of conversion (inhibiting polymerization).
3- Brown pigmentation in dentin.
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11- Clinical technique to minimize nano-leakage &
improve adhesive stability
1-Prolonged Curing Time
-extending curing time beyond 20 seconds results in:
√improve polymerization
√improve degree of conversion
√reducing the permeability
2- scrubbing action
Scrubbing action of self-etch adhesives results in:
Improve smear layer removal→ improve resin infiltration → improve enamel and dentinal bonding
→less nano-leakage
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3- Multiple layer adhesive application
Hashimoto et al. (2006) found that:
➢ Bond strength can be improved by applying three -coats of adhesive.
➢ Increasing the number of coats → minimize nano-leakage.
NB: Application of several coats without curing→ better resin impregnation
→minimize adhesive thickness
4-High-pressure air blowing
➢ Enhance solvent evaporation & resin penetration.
➢ More extended resin tags →Improve Bond strength.
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12- nano-adhesive releasing therapeutic ions
- Application of adhesives or pre-treatments doped with anti-MMPs → reduce
proteolytic enzymes & hydrolysis.
Ex: nano bioactive glasses (BGn) doped with therapeutic ions, such as Ag, F, Fe,Ca, and Cu.
1- Incorporation of bioactive glass doped with fluoride within adhesives results in:
✓ Better remineralization.
✓ Better MMP inhibition.
compared to bioglass
2- Incorporation of bioactive glass doped with copper CuBGn (2%) within adhesives results in:
✓ Induce remineralization.
✓ Inhibit MMP without affecting the bond strength.
Multi-functional nano-adhesive releasing therapeutic ions for MMP deactivation and remineralization. 2018
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13- Self healing adhesives
✓ Act by closing micro- or nanocracks.
✓ nanocapsules/ microcapsules filled with healing agent→
Crack → rupture of nanocapsules/ microcapsules →
release of their content → contacts the catalyst in the
matrix → polymerization → healing .
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12- Self healing adhesives
Example:
Poly(urea-formaldehyde) (PUF) microcapsules
containing TEGDMA and N,N-dihydroxyethyl-ptoluidine (DHEPT)
These capsules are incorporated into a matrix
containing nanoparticles of amorphous calcium
phosphate NACP to obtain crack-healing, antibacterial,
and remineralization
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