NOVEL STRATEGIES TO IMPROVE STABILIZATION OF
ADHESIVE INTERFACES
Outline:
What is hybrid layer
√ Causes of hybrid layer degradation
√ Novel strategies to improve stabilization of adhesive interfaces:
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
Adhesion of composite restorations occurs as a result of hybrid layer
formation …
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)
Causes of hybrid layer degradation
1- Degradation of Adhesive-Dentin Interface
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.
1.2. Chemical/Biochemical Interactions
pulpal pressure results in: pumping dentin fluid through dentinal
tubules
→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.
2- Microleakage
It occurs due to:
2.1 polymerization shrinkage:
(Contraction stresses  bond strength) → marginal gaps → microleakage
→ recurrent caries.
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 ethylmethacrylate:
✓ 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
4.Incomplete resin infiltration
→ leaves unprotected collagen and porosities in the hybrid layer.
Results in :
Incomplete water removal from interfibrillar spaces (between collagen
fibers) →water accumulation → hydrolysis → decreased bond strength
& increased nano leakage.
Consequences of bonding failure:
HYBRIDLAYER STABILIZATION
(1) Changing monomer structure
Aim :
Change the monomer structure to increase the hydrophobicity →
decrease water sorption.
The hydrophobicity of the monomers can be increased by
incorporating:
✓ Urethane group.
✓ Branched methacrylate linkage.
✓ Ethoxylated BisGMA.
(2) MMPs inhibitors
What are MMPs ?
✓ Proteolytic enzymes
✓ synthesized by odontoblasts and trapped within mineralized dentin
matrix.
✓ calcium-and zinc dependent
NB: Exposed dentin collagen express recognizable cleavage sites for
MMPs.
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.
This leads to:
1-loss of catalytic activity of MMPs .
2-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.
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.
a) Glutaraldehyde
*cross-linking by covalent bonds between amino groups of proteins and
the aldehyde groups of glutaraldehyde.
*5% glutaraldehyde for 1 min after acid etching →better bond stability.
* Disadvantage: toxic at high concentrations
b) Hesperidin
(Extracted from citrus fruits) → increase mechanical properties of hybrid
layer & immediate bond strength of self-etching adhesive
c) Riboflavin
*cross-linking agent in used with dental blue light
*Better bond stability.
*Biocompatible
d) Grape seed extract
*(GSE) is a natural cross-linker.
*Inhibit MMPs activity and production.
4-Galardin:
-Synthetic MMP inhibitor
-Attack the active sites and chelate the zinc ion in MMP
-Reduce nano-leakage
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.
(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?
because CQ is adversely affected by presence of acidic monomers in
Self-etch adhesives.
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).
(4)Novel resin formulation
(BisGMA) is the most common crosslinking monomer in dental
adhesives…
➔ Drawbacks: high susceptibility to hydrolysis → affect durability.
Modified formulations:
✓ Silyl-functionalized BisGMA.
✓ Resin containing γ-methacryloxyproyl trimethoxysilane (MPS).
1- Silyl-functionalized BisGMA
Ex: methoxysilyl-functionalized BisGMA.
silyl-BisGMA provide:
✓ higher crosslinking compared to BisGMA/HEMA formulations.
✓ hydrolysis resistance during aqueous aging.
Leading to….
➢ Decreased degradation
➢ Decreased leached HEMA by 90%
➢ Retain mechanical properties
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
(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.
• 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.
❖ ☺ amorphous calcium Phosphate nanoparticles (NACP) up
to 40 wt% provide Ca and P ion without affecting bond
strength.
• Hydroxyapatite
❖ ☺ 7 wt% nano HA improve the immediate micro-tensile
bond strength.
(6)Antibacterial Bond System
Bacteria→ secrete enzymes → demineralization → microleakage
and recurrent caries
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 , possessed 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.
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.
➔ Example for commercially available adhesive:
- G-ænial Bond
*Generally, Self-etch adhesives showed higher antibacterial
activity than total etch adhesives.
(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.
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
(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 .
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
(9) Ethanol wet bonding
Severe drying leads to collagen collapse
→ So, we need moist dentin for 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
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
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.
(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)
(2) Nonspecific Synthetic Cross-Linking Agents :
Cross-linking agents:
√ Stabilizes the structure.
√ Make it more resistant 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.
(4) Cross-Linking Agents of Natural Origin.
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.
(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
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.
(12) nano-adhesive releasing therapeutic ions
- Application of adhesives or pre-treatments doped with antiMMPs → reduce proteolytic enzymes & hydrolysis.
Ex: nano bioactive glasses (BGn) doped with specific functional
and 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.
(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
.
Example:
Poly(urea-formaldehyde) (PUF) microcapsules containing
TEGDMA and N,N-dihydroxyethyl-p-toluidine
(DHEPT)
These capsules are incorporated into a
matrix containing nanoparticles of
amorphous calcium phosphate NACP
to obtain crack-healing, antibacterial, and
remineralization
Thank you