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Bioactive and biomimetic
material
Presented By: Syed Manzoor Ul Haq
Dept of endodontics KVG dental college
Contents
• Introduction
• Definition
• Applications
• Various Biomimetic And Bioactive Materials
• Conclusion
• Refrences
INTRODUCTION
• In every field of dentistry and medicine, bioactive materials have
been widely used.
• These materials are used for regeneration, repair, and reconstruction
in the field of conservative dentistry and endodontics.
• Used in different forms and composition and act directly on vital
tissue, helping in its healing and repair.
• Directly function because of induction of various growth factors and
different cells.
• Such materials can form a surface layer of an apatite-like substance in
the presence of an inorganic phosphate solution.
• Their applications in dentistry include remineralization of dentin,
maintenance of long-term bonded restorations, and repair of
intrabony defects.
Definition
Biomimetics, term was coined
by Otto Schmitt in the 1950s .
Biomimetic is defined as the
study of the structure and
function of biological systems as
models for the design and
engineering of materials and
machines.
• Karma M, et al. Biomimetics in dentistry. Indian J Dent Edu
A bioactive material is one that
elicits a specific biological
response at the interface of the
material which results in the
formation of a bond between
the tissues and the material.
Hench LL, Splinter RJ, Allen WC, Greenlee TK Jr.; Bonding
mechanisms at the
interface of ceramic prosthetic materials. J Biomed Mater Res.,
1972; 2:117-141
Applications of Bioactive Materials and Molecules
in Dentistry
Root Canal Therapy
• Portland cement or MTA is a bioactive material used for maintaining
pulp and periodontal tissue vitality as part of pulp-capping and
perforation repair procedures.
• Mineral trioxide aggregate is also used as an obturating material after
root canal therapy. It helps in apexification.
Tooth Repair and Regeneration
• Dentin extracellular matrix proteins (ECMPs) contain growth factors
that can promote tooth healing and pulp regeneration.
• Dentonin (peptide) can stimulate reparative mineralization of the
coronal pulp and occlusion of the lumen of the root canal.
• A novel biomaterial (tissue regenerative gel), can promote the
regeneration of tooth tissue.
In Dental Surgery and Craniomaxillofacial
Reconstruction
• Biomaterials, such as Emdogain containing Porcine proteins play an
important role in periodontal regeneration after injury.
• Synthetic bone materials are used for maxillofacial and craniofacial
reconstruction.
• The ideal biomaterial for dental reconstruction should be
biocompatible and also able to maintain volume and can be easily
shaped.
• n-Butyl-2-cyanoacrylate is widely used as a tissue adhesive. It is also
used for filling and repairing bone defects.
Coating of Implants
Dental implants are made from titanium alloys and have a coating of
hydroxyapatite to promote osteogenesis and bone healing.
Hypersensitivity
• A novel bioactive glass-ceramic (biosilicate) is applied in
hypersensitivity cases.
• It is capable of inducing HCA (hydroxyl carbonate apatite) deposition
in open dentinal tubules, and thus occluding the dentinal tubules.
• Hence, biosilicate may be a new way for treating dentin
hypersensitivity.
Biomedical
Stem Cell Therapy
• New methods of stem cells with bioactive materials renovate the
function of injured tissue by replacing dead or damaged cells with
new and healthy cells.
• Dental Tissue Regeneration
• A combination of nanostructure materials, such as biomimetic
matrices and scaffold and stem cells, will certainly increase the
regenerative impact of dental pathological tissues
• Bone Graft
• Bioactive materials, such as osteoconductive matrix, which act as
scaffold to new bone growth, and osteoinductive proteins, which
support mitogenesis of undifferentiated cells combined with
osteogenic cells (mesenchymal stem cells), are capable of forming
bones.
• Drug Delivery
• Mesoporous, which are silica based, are widely used in drug delivery
and bone tissue engineering.
• The adequate combination of the synthesis techniques, additives, and
template systems leads to the improvement of materials that
combine the bioactive behavior with the drug carrier ability.
• Cosmetic Surgery
Collagen is used in soft tissue repair for augmentation in cosmetic
surgery.
• Tissue Engineering
Gelatin is used as a natural polymer, which is derivative of collagen.
Biomolecules released from gelatin are capable of maintaining their
biological activity and help them in tissue engineering
The ideal properties of bioactive material
• Bactericidal And Bacteriostatic
• Sterile
• Stimulate Reparative Dentine Formation
• Sterile And Maintain Pulp Vitality.
Various biomimetic and bioactive materials
are:
• Glass Ionomer Cement (GIC)
• Resin Based Composite
• Smart Dentin Replacement (SDR)
• Ceramic
• Castor Oil Bean Cement
• Calcium Hydroxide
• MTYA1-Ca filler
• Calcium Sulfate
• Calcium Phosphate
• Calcium Enriched Mixture (CEM)
• Mineral Trioxide Aggregate (MTA)
• Calcium Aluminate Cement
• Doxadent
• Ceramir
• Biodentine™
• Theracal
• Bioaggregate (BA)
• Endosequence Root Repair Material (ERRM) putty, ERRM paste RRM
putty fast set (FS) and iroot FS
• Bioceramic Sealers
• Bioceramic Gutta-Percha
• Bioactive Glass (BAG)
• Remineralizing Agents
• Casein phosphopeptide amorphous calcium phosphate (CPP-ACP)
• Demineralized dentin (dDM)
• Enamel matrix derivative (EMD)
• Growth Factors
• Bone Morphgenic Proteins (BMP)
• Platelet Concentrates
• Polyhedral Oligomeric Silsesquioxanes (POSS)
• Metallic Biomaterials
• Implant Biomaterials/Biomimetic Coatings on Implants
• Polymers
• Root Canal Revascularization via Blood Clot
Smart Materials
• A) Smart pressure bandages
• B) Smart suture
• C) Hydrogel
• D) Smart composites containing amorphous calcium phosphate (ACP)-
• E) Cercon
Glass Ionomer Cement (GIC)
• Glass ionomer cement (GIC) which was invented in 1969 is composed
of fluoroaluminosilicate glass powder and water soluble polymer
(acids).
• When powder and liquid is blended, it undergoes hardening reaction
that involves neutralization of the acidic group together with
significant release of fluorides.
• Bioactive formulation (such as 45S5, S53P4) has bioactive glass and
hydroxyapatite.
• The mechanical properties of GIC have been improved with
incorporation of metals such as stainless steel and bio inert ceramics
like zirconia.
• KT-308 (GC Corporation Company, Tokyo, Japan) a GIC sealers,
provides more resistance to coronal ingress of bacteria into the root
canal system.
• Active Gutta-Percha (GP) (Brasseler USA, Savannah, GA,
USA) has GI impregnated Gutta-Percha (GP) cones that
are bondable to GIC based sealer and claims to offer
adhesive bonding of the active GP to intraradicular
dentine
• ZUT (University of Toronto, Ontario, Canada) a
combination of GIC and an antimicrobial silver-
containing zeolite is effective against E.faecalis and
hence can be more effective in treating teeth of
persistent apical periodontitis .
Resin Based Composite
• Introduced by Bowen in 1962, offers wear resistance, color stability,
improved physical properties and radiopacity
Smart Dentin Replacement (SDR)
• Smart Dentine Replacement is a first flowable
composite material.
• Its characterized by low polymerization stress,
low polymerization shrinkage, high depth of cure
and bulk-fill material in increments of up to 4
mm in class i and ii cavities.
Castor Oil Bean Cement
• It consists of 81 to 96% triglyceride of ricinoleic acid and is
considered a natural polyol containing three hydroxyl radicals and can
be used as a pulp-capping material.
Calcium Hydroxide
• In 1928, Calcium Hydroxide was introduced by
Hermann in dentistry.
• It has been widely used as a mineralizing agent
and antimicrobial agent.
• Calcium hydroxide causes release of extracellular
matrix molecules (like dentine phosphoproteins,
dentine sialoproteins), raises expression of
biomolecules, like BMP, and has antimicrobial
and anti-inflammatory action
• Formation of tunnel defects and decrease in dentine strength
following its long term use as intracanal medicament are its
limitations.
• To improve its biological performance, Controlled-release Calcium
hydroxide loaded microcapsules based on polylactic acid (PLA) and
ethyl cellulose (EC) have been developed.
• These formulations prolonged ion release.
MTYA1-Ca filler
It is a resin-based direct pulp-capping agent.
Composition:
 Powder :89.0% microfiller, 10.0% calcium hydroxide, and 1.0% benzoyl
peroxide
 Liquid : 67.5% triethyleneglycol dimethacrylate, 30.0% glyceryl
methacrylate, 1.0% O-methacryloyl tyrosine amide, 1.0%
dimethylaminoethylmethacrylate, and 0.5% camphorquinone
MTYA1-Ca developed dentine bridge formation without formation of a
necrotic layer, revealed to have good physical properties, and was not
inferior to Dycal histopathologically.
Niinuma A. Int Endod J. 1999
Calcium Sulfate
• Calcium sulfate (CS) has been shown to be
completely bio absorbable, osteoconductive,
allow fibroblast migration, do not cause an
inflammatory response
• It also do not elevate serum calcium levels.
• Recently, it has been shown that CS can be
manufactured into a granular composite of CS and
poly-l-lactic acid to decrease the degradation rate.
Calcium Phosphate
• Calcium phosphates plays important role in
biological and pathological mineralization.
• Most commonly used in the form of paste,
cement, ceramics and scaffold.
• It helps in induction of bridge formation with
no superficial tissue necrosis and significant
absence of pulpal inflammation.
The following are calcium phosphate materials
Calcium Enriched Mixture (CEM)
• It contains calcium oxide, sulfur trioxide, phosphorous pentoxide, and
silicon dioxide.
• It might promote differentiation of stem cells and cementogenesis.
• It is also known as NEC (new endodontic cement) and was introduced
by Asgary.
Bio ceramic based material/tricalcium silicate
(calcium silicate based materials)
• MTA which was developed by Mahmoud Torabinejad
at Loma Linda University, consists of 50-75 % (wt.)
calcium oxide and 15-25 % silicon dioxide.
 It has high pH (12.5),
• causes regeneration of the periodontal ligament (PDL)
• dentinal bridge formation
• biomineralisation and stimulation of cell differentiation
• has antimicrobial activity.
 However, difficulty in manipulation and longer setting
time are its limitations
• i). MTA angelus (Aangelus, Londrina, PR, Brazil)
is composed of 80% Portland cement and 20%
bismuth oxide and has setting time of 14
minutes.
• ii) MTA fillapex (angelus solutions odonatological, Londrina, PR, Brazil)
is a calcium silicate-based bio ceramic sealer, created with an attempt
to incorporate physical and chemical properties of a resin-based root
canal sealer and the biological properties of MTA.
• iii). MTA plus (Avalon biomed Inc.,
Bradenton, FL, USA) is a fine powder root
canal sealer with composition similar to
ProRoot MTA .
• iv). Pozzolan cement (Endocem) (Maruchi, Wonju, Korea) is a fast
setting MTA derived material which does not contain any chemical
accelerator.
Calcium Aluminate Cement
• (Binderware, São Carlos, SP, Brazil), was developed by the Federal
University of São Carlos.
• It is composed of oxides of aluminium (Al2O3), calcium, (CaO), silicon
(SiO2), magnesium(MgO) and iron (Fe2O3).
• It allows the control of impurities such as Fe2O3(which promotes tooth
darkening) and is free of MgO and CaO which restricts the undesirable
expansion of the material upon moisture contact.
Doxadent
• It is a calcium aluminate product available in powder liquid form.
• It can be used as a permanent restorative material.
• It consists of alumina, calcium oxide, water, zirconium dioxide and other
alkali oxides.
• When powder and liquid are mixed water dissolves the calcium aluminate
powder leading to the formation of calcium, aluminum and hydroxyl ions
leading to the formation of katoite and gibbsite.
Ceramir
• It is calcium aluminate cement used as a
luting agent.
• It works on the principle of two cements
they are calcium aluminate and glass
ionomer cement.
• This cement helps in luting of permanent
crowns and fixed partial dentures, gold
inlays and onlays, prefabricated metal
and cast dowel and cores, and high-
strength all-zirconia or all-alumina
crowns
Biodentine™
• (Septodont, Saint-Maur-des-Fossés, France),
introduced in 2011.
• It is a bioactive dentin replacement material
having similar properties of dentin and has a
positive effect on vital pulp cells stimulating
tertiary dentin formation
• Powder
• Tri-calcium silicate
• Di-calcium silicate
• Calcium carbonate & oxide
• Iron oxide
• Zirconium oxide
• Liquid
• Calcium chloride
• Hydrosoluble polymer
• When biodentine comes in contact with dentine it results into
formation of the tag-like structures and is called ‘‘Mineral Infiltration
Zone,’’ which may contribute to adhesive properties.
• It has improved- physical properties,
-reduced setting time (12 min)
-induces odontoblast-like cell differentiation
-mineralization
• Mineralization occurs in the form of osteodentine by expressing
markers of odontoblasts & increases TGF-Beta1 secretion from pulpal
cells enabling early mineralization.
• During the setting of the cement Calcium hydroxide is formed. Due to
its high pH, Calcium hydroxide causes irritation at the area of
exposure.
Theracal
• It is a light-cured, resin-modified calcium silicate–filled liner insulating
and protecting the dentin–pulp complex.
• It can be used in direct and indirect pulp capping, as a protective
base/liner under composites, amalgams, cements, and other base
materials.
• When this material was compared with ProRoot MTA and Dycal, it
was found that calcium release was higher and solubility was low.
Bioaggregate (BA)
• Innovative Bioceramix Inc., Vancouver,
BC, Canada) introduced in 2006
• It is delivered as powder form of
nanoparticles containing tricalcium
silicate dicalcium silicate calcium
phosphate monobasic amorphous
silicon dioxide tantalum pentoxide
(radio pacifier) while it’s liquid form
contains deionized water.
• It is aluminum free formulation, thus it stimulates proliferation of
human PDL fibroblasts and aids in periodontal regeneration.
• Used for pulp capping, apexification, root resorption, root perforation
and root end filling material.
Endosequence Root Repair Material (ERRM) putty, ERRM paste
RRM putty fast set (FS) and iroot FS
Endosequence root repair
material (ERRM) (Brasseler USA,
Savannah, GA)
 delivered as
 premixed mouldable putty (iRoot
BP Plus) or
 as a preloaded paste in a syringe
with delivery tips for intracanal
placement.
It contains calcium phosphate
monobasic, calcium silicates,
zirconium oxide and tantalum
oxide.
• Inside dentinal tubules, ERRM forms tag-like structures .
• They are premixed, single component materials which is ready to use
from the syringe or a tiny screw-cap box and does not requires
mixing, thus differentiating it from MTA, bioaggregate and biodentine.
• RRM putty fast set (FS) has the initial setting time of 20 min.
• iRoot FS (Brasseler USA, Savannah, GA) is iRoot series material with
improved handling properties and shorter setting time
Ceramics
Ceramics are nonorganic, nonmetallic, non-polymeric materials
manufactured by compacting and sintering at elevated temperatures.
They are being examined for bone tissue engineering and also have
dental applications.
 Hydroxyapatite (HA), a major inorganic component of bone is a
calcium phosphate based ceramic.
In Novel ceramic bone replacement material Ceraball, new bone
formation first takes place on the scaffold surface.
• Ceraballs may act as a carrier for pluripotent mesenchymal stem
cells, stromal cells and bone marrow
• On the basis of tissue’s response it can be classified as bioactive
(bioglass/glass ceramic), bioresorbable (calcium phosphate) and bio
inert (alumina, zirconia and carbon).
• The implant coating is intended for improving implant surface
biocompatibility profiles and longevity
Bioceramic Sealers
• Endosequence BC sealer
(Brasseler USA, Savannah, GA) or iRoot
SP root canal sealer (Innovative
Bioceramix Inc., Vancouver, BC, Canada) is
premixed bioceramic endodontic sealer
containing tricalcium silicate, zirconium
oxide, dicalcium silicate,calcium phosphate
monobasic, colloidal silica, calcium silicates
and calcium hydroxide
• The iRoot SP possesses high pH,
hydrophilicity, and active calcium
hydroxide release
Bioceramic Gutta-Percha
• These are Gutta-Percha cones impregnated and coated with
bioceramic nanoparticles and are verified with laser for tip and taper
accuracy.
• Such cones with BC sealers allows “three-dimensional” bonded
obturation.
Bioactive Glass (BAG)
• Calcium sodium phosphosilicate is used in cariology, restorative
dentistry and periodontology, air polishing procedures, desensitizing
toothpastes, and as a bonding and bone regeneration material
• Mohn et al mixed BAG particles with 50% bismuth oxide and used it as
root canal filling material. BAG has directly and indirectly pH related
antibacterial effect.
• BAG can be the material of choice for pulp capping & periapical bone
healing because it is biocompatible & has antibacterial property.
Schepers et al, 1991
• BAG produce Less inflammation, dentin bridge formation & no
internal resorption, necrosis or abscess compared to Ca(OH)2
Journal of Dentistry, Tehran University of Medical Sciences, Tehran, Iran(2007)
• Bioactive glass treatment leads to enhanced apatite formation in
dentin. Size of the bioactive glass powder particles influences the rate
of apatite formation with nano bioactive glass powders having faster
apatite forming kinetics
D. Fernando, et al, (2017)
Remineralizing Agents
Casein phosphopeptide amorphous calcium phosphate
(CPP-ACP):
• Subsurface carious lesion can remineralize through diffusion of
calcium and phosphate ions into tooth structure.
• CPP stabilizes calcium and phosphate in solution state and thus acts
as calcium and phosphate reservoir.
• The incorporation of the CPP-ACP
nanoparticles into the cross-linked
matrix of the GIC aids to increase
compressive strength, microtensile
bond strength and enhances release
of calcium, phosphate and fluoride
ions.
• Tooth Mousse™ (Europe and
Australasia) or MI Paste™ (USA and
Japan) contains 10% w/w CPP-ACP
nanocomplexes.
Demineralized dentin (dDM)
• The dentin matrix which are used for implant biomaterial has
osteogenic and chemotactic potential.
• Demineralized bone matrix when comes in contact with mesenchymal
cells it induces chondrogenesis and osteogenesis.
• Incorporation of Galla chinensis extract into dentin matrix may
improve biochemical and biomechanical properties.
Enamel matrix derivative (EMD)
• Enamel matrix derivative is derived from
pig enamel matrix (Emdogain;
Straumann AG, Basel, Switzerland)
• It has been employed in patients with
severe attachment loss through
recruitment of cementoblasts on to the
root-surface to restore functional
periodontal ligament, cementum and
alveolar bone.
Growth factors
• Growth factors are considered as engines that drive wound healing.
Platelet derived growth factor (PDGF) plays key role in chemotaxis of
neutrophils that acts with other growth factors to produce collagen.
• Keratinocyte growth factor (KGF) through keratinocyte differentiation,
plays vital role in wound re-epithelialization.
• Transforming growth factor (TGF) induces extracellular matrix
deposition and collagen formation.
• Fibroblast growth factor (FGF) plays role in fibroblast proliferation,
angiogenesis, and matrix deposition.
• Vascular endothelial growth factor (VEGF) increases vascular
permeability at the capillary level.
• Epidermal growth factors (EGF) acts in an autocrine fashion.
• Kepivance (KGF-2) is used in preventing oral mucositis. Juvista, a
recombinant TGF-b3 may be used as a growth factor enhancer for all
surgically created wounds
Bone Morphgenic Proteins (BMP)
• BMP plays a key role in dental bone grafting and implant placement,
fracture healing and spinal fusion.
• It increases alkaline phosphatase activity, stimulates proteoglycan
synthesis in chondroblasts, collagen synthesis in osteoblasts,
differentiation of neural cells and chemo taxis of monocytes.
Platelet Concentrates
• It was first described by Whitman et all.
• Platelet rich plasma (PRP) is generated by differential centrifugation
and serves as reservoir of critical growth factors such as platelet-
derived growth factor (PDGF), transforming growth factor-b (TGF-B) and
insulin-like growth factor-1 (IGF-1) , thus regulates wound-healing.
• PRP requires biochemical blood handling with addition of
anticoagulants while platelet rich fibrin (PRF) does not.
• A second generation platelet concentrate, Leucocyte and platelet rich
fibrin (L-PRF) was developed by Choukroun et al in France does not
contain any anticoagulant or gellifying agents.
Polyhedral Oligomeric Silsesquioxanes (POSS)
• Biomaterials such as polyhedral oligomeric silsesquioxanes (POSS)
and polyhedral oligomeric silicates (POS) may be fabricated by the
incorporation of POSS molecules to provide a nanoscopic topology
which favors cellular modulation, bioavailability and differentiation.
• Advent of POSS has led to formulation of dental adhesives and
composites with improved mechanical and physical properties.
Metallic Biomaterials
• Metallic biomaterials are mainly used for fabrication of medical
devices for hard tissue replacement such as artificial hip joints, bone
plates and dental implants.
• Stainless steel, cobalt alloys, pure Ti and Ti-6al-4v are mainly used for
biomedical applications.
Implant Biomaterials/Biomimetic Coatings on
Implants
• It includes metals and metallic alloys,
ceramics, natural materials and synthetic
polymers.
• Metals and metallic alloys include titanium,
tantalum and alloy of Ti-Al-Va, Co-Cr-Mb, Fe-
Cr-Ni. Devices made from zirconium,
hafnium and tungsten have been evaluated
recently.
• Hydroxyapatite-coated metal’s coating is
done using robotic techniques for
osteoconductivity.
Polymers
• Polymers like polymethylmethacrylate (PMMA), polyethylene (PE),
polyurethanes are used in dental surgery since decades.
• Polyglycolic acid (PGA), polylactide (PLA), polydioxanone (PDS) are
mainly used as resorbable bone fixation devices or as suture
materials.
• For surgical wound repair fibrin glue is used as tissue adhesive.
• Alginate can be used as growth factor delivery system.
Regenerative endodontics and tissue engineering
• Dental regeneration is a process in humans by which specialized
dental tissues are replaced by the recruitment, proliferation,
migration, and differentiation of dental stem cells.
• Stem cells, scaffolds, and growth factors are 3 key elements for tissue
regeneration.
• Root Canal Revascularization via Blood Clot
In the Root canal revascularization via blood clot in apical region, the
bioceramic material is placed as mid-root/coronal plug, thereby
providing permanent and superior quality seal.
• Jung et al. reported that by activation of MAPK pathway biodentine,
bioaggregate and MTA causes odontoblastic differentiation and mineralization.
• Postnatal stem cell therapy, pulp implantation, scaffold implantation, injectable
scaffold delivery, 3-D cell printing and gene therapy are some regenerative
approaches.
Smart Materials
• It is defined as the class of materials that are highly responsive and
have the inherent capability to sense and react according to changes
in the environment.
• They can be classified as active and passive smart materials.
• Passive smart materials responds to external change without any
external control.
• While active smart materials utilizes a feedback loop to enable them
to function like a cognitive response through an actuator circuit.
A) Smart pressure bandages - Upon
exposure to blood, these bandages
contracts thereby putting pressure on
a wound.
B) Smart suture - It ties itself into the
Perfect knot and possesses shape
memory.
C) Hydrogel - It exhibit plastic contraction upon changes in
temperature, pH, magnetic or electrical field.
D) Smart composites containing amorphous calcium phosphate (ACP)-
Inclusion of ACP into composite resin results into release of calcium
and phosphorous for an extended period and are thus helpful in caries
prevention.
• E) Cercon - smart ceramics - It is
a metal-free biocompatible life
like restoration that has
strength to resist crack
formation.
• The drawbacks of porcelain
fused to metal like unsightly
dark margins and artificial grey
shadows from the underlying
metal are no longer a problem
with Cercon.
Conclusion
• Biomimietic materials functions as root canal sealer, filling materials,
cements and root and crown repair material and possesses features
as like strengthening the root following obturation, good sealing
ability, enhanced biocompatibility and antibacterial properties.
• Contemporary biomaterials have shown ability to overcome the
limitations of traditional materials.
• However, there exists limitations when considering criteria for
categorizing them as ideal materials.
• Several in vitro and in vivo studies have demonstrated good results,
however randomized and double blind studies of sufficient duration
with biomimetic materials have been needed to confirm long term
success.
REFRENCES
• Cohen's Pathways of the Pulp, 11th Edition
• Sonarkar S, Purba R. Bioactive materials in conservative dentistry. Int J
Contemp Dent Med Rev. 2015;2015:4.
• Madfa AA, Al-Sanabani FA, Al-Kudami NH. Endodontic Repair Filling
Materials: A Review Article.
• Bhushan M, Tyagi S, Nigam M, Choudhary A, Khurana N, Dwivedi V.
Bioactive materials: A short review. J. Orofac. Res. 2015 Oct;5:138-41.
• Jefferies S. Bioactive and biomimetic restorative materials: a
comprehensive review. Part II. Journal of Esthetic and Restorative
Dentistry. 2014 Jan 1;26(1):27-39.
Thank you

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Bioactive and biomimitic material

  • 1. Bioactive and biomimetic material Presented By: Syed Manzoor Ul Haq Dept of endodontics KVG dental college
  • 2. Contents • Introduction • Definition • Applications • Various Biomimetic And Bioactive Materials • Conclusion • Refrences
  • 3. INTRODUCTION • In every field of dentistry and medicine, bioactive materials have been widely used. • These materials are used for regeneration, repair, and reconstruction in the field of conservative dentistry and endodontics. • Used in different forms and composition and act directly on vital tissue, helping in its healing and repair. • Directly function because of induction of various growth factors and different cells.
  • 4. • Such materials can form a surface layer of an apatite-like substance in the presence of an inorganic phosphate solution. • Their applications in dentistry include remineralization of dentin, maintenance of long-term bonded restorations, and repair of intrabony defects.
  • 5. Definition Biomimetics, term was coined by Otto Schmitt in the 1950s . Biomimetic is defined as the study of the structure and function of biological systems as models for the design and engineering of materials and machines. • Karma M, et al. Biomimetics in dentistry. Indian J Dent Edu A bioactive material is one that elicits a specific biological response at the interface of the material which results in the formation of a bond between the tissues and the material. Hench LL, Splinter RJ, Allen WC, Greenlee TK Jr.; Bonding mechanisms at the interface of ceramic prosthetic materials. J Biomed Mater Res., 1972; 2:117-141
  • 6. Applications of Bioactive Materials and Molecules in Dentistry Root Canal Therapy • Portland cement or MTA is a bioactive material used for maintaining pulp and periodontal tissue vitality as part of pulp-capping and perforation repair procedures. • Mineral trioxide aggregate is also used as an obturating material after root canal therapy. It helps in apexification.
  • 7. Tooth Repair and Regeneration • Dentin extracellular matrix proteins (ECMPs) contain growth factors that can promote tooth healing and pulp regeneration. • Dentonin (peptide) can stimulate reparative mineralization of the coronal pulp and occlusion of the lumen of the root canal. • A novel biomaterial (tissue regenerative gel), can promote the regeneration of tooth tissue.
  • 8. In Dental Surgery and Craniomaxillofacial Reconstruction • Biomaterials, such as Emdogain containing Porcine proteins play an important role in periodontal regeneration after injury. • Synthetic bone materials are used for maxillofacial and craniofacial reconstruction. • The ideal biomaterial for dental reconstruction should be biocompatible and also able to maintain volume and can be easily shaped. • n-Butyl-2-cyanoacrylate is widely used as a tissue adhesive. It is also used for filling and repairing bone defects.
  • 9. Coating of Implants Dental implants are made from titanium alloys and have a coating of hydroxyapatite to promote osteogenesis and bone healing. Hypersensitivity • A novel bioactive glass-ceramic (biosilicate) is applied in hypersensitivity cases. • It is capable of inducing HCA (hydroxyl carbonate apatite) deposition in open dentinal tubules, and thus occluding the dentinal tubules. • Hence, biosilicate may be a new way for treating dentin hypersensitivity.
  • 10. Biomedical Stem Cell Therapy • New methods of stem cells with bioactive materials renovate the function of injured tissue by replacing dead or damaged cells with new and healthy cells. • Dental Tissue Regeneration • A combination of nanostructure materials, such as biomimetic matrices and scaffold and stem cells, will certainly increase the regenerative impact of dental pathological tissues
  • 11. • Bone Graft • Bioactive materials, such as osteoconductive matrix, which act as scaffold to new bone growth, and osteoinductive proteins, which support mitogenesis of undifferentiated cells combined with osteogenic cells (mesenchymal stem cells), are capable of forming bones.
  • 12. • Drug Delivery • Mesoporous, which are silica based, are widely used in drug delivery and bone tissue engineering. • The adequate combination of the synthesis techniques, additives, and template systems leads to the improvement of materials that combine the bioactive behavior with the drug carrier ability.
  • 13. • Cosmetic Surgery Collagen is used in soft tissue repair for augmentation in cosmetic surgery. • Tissue Engineering Gelatin is used as a natural polymer, which is derivative of collagen. Biomolecules released from gelatin are capable of maintaining their biological activity and help them in tissue engineering
  • 14. The ideal properties of bioactive material • Bactericidal And Bacteriostatic • Sterile • Stimulate Reparative Dentine Formation • Sterile And Maintain Pulp Vitality.
  • 15. Various biomimetic and bioactive materials are: • Glass Ionomer Cement (GIC) • Resin Based Composite • Smart Dentin Replacement (SDR) • Ceramic • Castor Oil Bean Cement • Calcium Hydroxide • MTYA1-Ca filler • Calcium Sulfate
  • 16. • Calcium Phosphate • Calcium Enriched Mixture (CEM) • Mineral Trioxide Aggregate (MTA) • Calcium Aluminate Cement • Doxadent
  • 17. • Ceramir • Biodentine™ • Theracal • Bioaggregate (BA) • Endosequence Root Repair Material (ERRM) putty, ERRM paste RRM putty fast set (FS) and iroot FS
  • 18. • Bioceramic Sealers • Bioceramic Gutta-Percha • Bioactive Glass (BAG) • Remineralizing Agents • Casein phosphopeptide amorphous calcium phosphate (CPP-ACP) • Demineralized dentin (dDM) • Enamel matrix derivative (EMD) • Growth Factors • Bone Morphgenic Proteins (BMP)
  • 19. • Platelet Concentrates • Polyhedral Oligomeric Silsesquioxanes (POSS) • Metallic Biomaterials • Implant Biomaterials/Biomimetic Coatings on Implants • Polymers • Root Canal Revascularization via Blood Clot
  • 20. Smart Materials • A) Smart pressure bandages • B) Smart suture • C) Hydrogel • D) Smart composites containing amorphous calcium phosphate (ACP)- • E) Cercon
  • 21. Glass Ionomer Cement (GIC) • Glass ionomer cement (GIC) which was invented in 1969 is composed of fluoroaluminosilicate glass powder and water soluble polymer (acids). • When powder and liquid is blended, it undergoes hardening reaction that involves neutralization of the acidic group together with significant release of fluorides.
  • 22. • Bioactive formulation (such as 45S5, S53P4) has bioactive glass and hydroxyapatite. • The mechanical properties of GIC have been improved with incorporation of metals such as stainless steel and bio inert ceramics like zirconia. • KT-308 (GC Corporation Company, Tokyo, Japan) a GIC sealers, provides more resistance to coronal ingress of bacteria into the root canal system.
  • 23. • Active Gutta-Percha (GP) (Brasseler USA, Savannah, GA, USA) has GI impregnated Gutta-Percha (GP) cones that are bondable to GIC based sealer and claims to offer adhesive bonding of the active GP to intraradicular dentine • ZUT (University of Toronto, Ontario, Canada) a combination of GIC and an antimicrobial silver- containing zeolite is effective against E.faecalis and hence can be more effective in treating teeth of persistent apical periodontitis .
  • 24. Resin Based Composite • Introduced by Bowen in 1962, offers wear resistance, color stability, improved physical properties and radiopacity
  • 25.
  • 26. Smart Dentin Replacement (SDR) • Smart Dentine Replacement is a first flowable composite material. • Its characterized by low polymerization stress, low polymerization shrinkage, high depth of cure and bulk-fill material in increments of up to 4 mm in class i and ii cavities.
  • 27. Castor Oil Bean Cement • It consists of 81 to 96% triglyceride of ricinoleic acid and is considered a natural polyol containing three hydroxyl radicals and can be used as a pulp-capping material.
  • 28. Calcium Hydroxide • In 1928, Calcium Hydroxide was introduced by Hermann in dentistry. • It has been widely used as a mineralizing agent and antimicrobial agent. • Calcium hydroxide causes release of extracellular matrix molecules (like dentine phosphoproteins, dentine sialoproteins), raises expression of biomolecules, like BMP, and has antimicrobial and anti-inflammatory action
  • 29. • Formation of tunnel defects and decrease in dentine strength following its long term use as intracanal medicament are its limitations. • To improve its biological performance, Controlled-release Calcium hydroxide loaded microcapsules based on polylactic acid (PLA) and ethyl cellulose (EC) have been developed. • These formulations prolonged ion release.
  • 30. MTYA1-Ca filler It is a resin-based direct pulp-capping agent. Composition:  Powder :89.0% microfiller, 10.0% calcium hydroxide, and 1.0% benzoyl peroxide  Liquid : 67.5% triethyleneglycol dimethacrylate, 30.0% glyceryl methacrylate, 1.0% O-methacryloyl tyrosine amide, 1.0% dimethylaminoethylmethacrylate, and 0.5% camphorquinone MTYA1-Ca developed dentine bridge formation without formation of a necrotic layer, revealed to have good physical properties, and was not inferior to Dycal histopathologically. Niinuma A. Int Endod J. 1999
  • 31. Calcium Sulfate • Calcium sulfate (CS) has been shown to be completely bio absorbable, osteoconductive, allow fibroblast migration, do not cause an inflammatory response • It also do not elevate serum calcium levels. • Recently, it has been shown that CS can be manufactured into a granular composite of CS and poly-l-lactic acid to decrease the degradation rate.
  • 32. Calcium Phosphate • Calcium phosphates plays important role in biological and pathological mineralization. • Most commonly used in the form of paste, cement, ceramics and scaffold. • It helps in induction of bridge formation with no superficial tissue necrosis and significant absence of pulpal inflammation.
  • 33. The following are calcium phosphate materials
  • 34. Calcium Enriched Mixture (CEM) • It contains calcium oxide, sulfur trioxide, phosphorous pentoxide, and silicon dioxide. • It might promote differentiation of stem cells and cementogenesis. • It is also known as NEC (new endodontic cement) and was introduced by Asgary.
  • 35. Bio ceramic based material/tricalcium silicate (calcium silicate based materials) • MTA which was developed by Mahmoud Torabinejad at Loma Linda University, consists of 50-75 % (wt.) calcium oxide and 15-25 % silicon dioxide.  It has high pH (12.5), • causes regeneration of the periodontal ligament (PDL) • dentinal bridge formation • biomineralisation and stimulation of cell differentiation • has antimicrobial activity.  However, difficulty in manipulation and longer setting time are its limitations
  • 36. • i). MTA angelus (Aangelus, Londrina, PR, Brazil) is composed of 80% Portland cement and 20% bismuth oxide and has setting time of 14 minutes.
  • 37. • ii) MTA fillapex (angelus solutions odonatological, Londrina, PR, Brazil) is a calcium silicate-based bio ceramic sealer, created with an attempt to incorporate physical and chemical properties of a resin-based root canal sealer and the biological properties of MTA.
  • 38. • iii). MTA plus (Avalon biomed Inc., Bradenton, FL, USA) is a fine powder root canal sealer with composition similar to ProRoot MTA .
  • 39. • iv). Pozzolan cement (Endocem) (Maruchi, Wonju, Korea) is a fast setting MTA derived material which does not contain any chemical accelerator.
  • 40. Calcium Aluminate Cement • (Binderware, São Carlos, SP, Brazil), was developed by the Federal University of São Carlos. • It is composed of oxides of aluminium (Al2O3), calcium, (CaO), silicon (SiO2), magnesium(MgO) and iron (Fe2O3). • It allows the control of impurities such as Fe2O3(which promotes tooth darkening) and is free of MgO and CaO which restricts the undesirable expansion of the material upon moisture contact.
  • 41. Doxadent • It is a calcium aluminate product available in powder liquid form. • It can be used as a permanent restorative material. • It consists of alumina, calcium oxide, water, zirconium dioxide and other alkali oxides. • When powder and liquid are mixed water dissolves the calcium aluminate powder leading to the formation of calcium, aluminum and hydroxyl ions leading to the formation of katoite and gibbsite.
  • 42. Ceramir • It is calcium aluminate cement used as a luting agent. • It works on the principle of two cements they are calcium aluminate and glass ionomer cement. • This cement helps in luting of permanent crowns and fixed partial dentures, gold inlays and onlays, prefabricated metal and cast dowel and cores, and high- strength all-zirconia or all-alumina crowns
  • 43. Biodentine™ • (Septodont, Saint-Maur-des-Fossés, France), introduced in 2011. • It is a bioactive dentin replacement material having similar properties of dentin and has a positive effect on vital pulp cells stimulating tertiary dentin formation
  • 44. • Powder • Tri-calcium silicate • Di-calcium silicate • Calcium carbonate & oxide • Iron oxide • Zirconium oxide • Liquid • Calcium chloride • Hydrosoluble polymer
  • 45. • When biodentine comes in contact with dentine it results into formation of the tag-like structures and is called ‘‘Mineral Infiltration Zone,’’ which may contribute to adhesive properties. • It has improved- physical properties, -reduced setting time (12 min) -induces odontoblast-like cell differentiation -mineralization
  • 46. • Mineralization occurs in the form of osteodentine by expressing markers of odontoblasts & increases TGF-Beta1 secretion from pulpal cells enabling early mineralization. • During the setting of the cement Calcium hydroxide is formed. Due to its high pH, Calcium hydroxide causes irritation at the area of exposure.
  • 47. Theracal • It is a light-cured, resin-modified calcium silicate–filled liner insulating and protecting the dentin–pulp complex. • It can be used in direct and indirect pulp capping, as a protective base/liner under composites, amalgams, cements, and other base materials. • When this material was compared with ProRoot MTA and Dycal, it was found that calcium release was higher and solubility was low.
  • 48. Bioaggregate (BA) • Innovative Bioceramix Inc., Vancouver, BC, Canada) introduced in 2006 • It is delivered as powder form of nanoparticles containing tricalcium silicate dicalcium silicate calcium phosphate monobasic amorphous silicon dioxide tantalum pentoxide (radio pacifier) while it’s liquid form contains deionized water.
  • 49. • It is aluminum free formulation, thus it stimulates proliferation of human PDL fibroblasts and aids in periodontal regeneration. • Used for pulp capping, apexification, root resorption, root perforation and root end filling material.
  • 50. Endosequence Root Repair Material (ERRM) putty, ERRM paste RRM putty fast set (FS) and iroot FS Endosequence root repair material (ERRM) (Brasseler USA, Savannah, GA)  delivered as  premixed mouldable putty (iRoot BP Plus) or  as a preloaded paste in a syringe with delivery tips for intracanal placement. It contains calcium phosphate monobasic, calcium silicates, zirconium oxide and tantalum oxide.
  • 51. • Inside dentinal tubules, ERRM forms tag-like structures . • They are premixed, single component materials which is ready to use from the syringe or a tiny screw-cap box and does not requires mixing, thus differentiating it from MTA, bioaggregate and biodentine. • RRM putty fast set (FS) has the initial setting time of 20 min. • iRoot FS (Brasseler USA, Savannah, GA) is iRoot series material with improved handling properties and shorter setting time
  • 52. Ceramics Ceramics are nonorganic, nonmetallic, non-polymeric materials manufactured by compacting and sintering at elevated temperatures. They are being examined for bone tissue engineering and also have dental applications.  Hydroxyapatite (HA), a major inorganic component of bone is a calcium phosphate based ceramic. In Novel ceramic bone replacement material Ceraball, new bone formation first takes place on the scaffold surface. • Ceraballs may act as a carrier for pluripotent mesenchymal stem cells, stromal cells and bone marrow
  • 53. • On the basis of tissue’s response it can be classified as bioactive (bioglass/glass ceramic), bioresorbable (calcium phosphate) and bio inert (alumina, zirconia and carbon). • The implant coating is intended for improving implant surface biocompatibility profiles and longevity
  • 54. Bioceramic Sealers • Endosequence BC sealer (Brasseler USA, Savannah, GA) or iRoot SP root canal sealer (Innovative Bioceramix Inc., Vancouver, BC, Canada) is premixed bioceramic endodontic sealer containing tricalcium silicate, zirconium oxide, dicalcium silicate,calcium phosphate monobasic, colloidal silica, calcium silicates and calcium hydroxide • The iRoot SP possesses high pH, hydrophilicity, and active calcium hydroxide release
  • 55. Bioceramic Gutta-Percha • These are Gutta-Percha cones impregnated and coated with bioceramic nanoparticles and are verified with laser for tip and taper accuracy. • Such cones with BC sealers allows “three-dimensional” bonded obturation.
  • 56. Bioactive Glass (BAG) • Calcium sodium phosphosilicate is used in cariology, restorative dentistry and periodontology, air polishing procedures, desensitizing toothpastes, and as a bonding and bone regeneration material • Mohn et al mixed BAG particles with 50% bismuth oxide and used it as root canal filling material. BAG has directly and indirectly pH related antibacterial effect.
  • 57. • BAG can be the material of choice for pulp capping & periapical bone healing because it is biocompatible & has antibacterial property. Schepers et al, 1991 • BAG produce Less inflammation, dentin bridge formation & no internal resorption, necrosis or abscess compared to Ca(OH)2 Journal of Dentistry, Tehran University of Medical Sciences, Tehran, Iran(2007) • Bioactive glass treatment leads to enhanced apatite formation in dentin. Size of the bioactive glass powder particles influences the rate of apatite formation with nano bioactive glass powders having faster apatite forming kinetics D. Fernando, et al, (2017)
  • 58. Remineralizing Agents Casein phosphopeptide amorphous calcium phosphate (CPP-ACP): • Subsurface carious lesion can remineralize through diffusion of calcium and phosphate ions into tooth structure. • CPP stabilizes calcium and phosphate in solution state and thus acts as calcium and phosphate reservoir.
  • 59. • The incorporation of the CPP-ACP nanoparticles into the cross-linked matrix of the GIC aids to increase compressive strength, microtensile bond strength and enhances release of calcium, phosphate and fluoride ions. • Tooth Mousse™ (Europe and Australasia) or MI Paste™ (USA and Japan) contains 10% w/w CPP-ACP nanocomplexes.
  • 60. Demineralized dentin (dDM) • The dentin matrix which are used for implant biomaterial has osteogenic and chemotactic potential. • Demineralized bone matrix when comes in contact with mesenchymal cells it induces chondrogenesis and osteogenesis. • Incorporation of Galla chinensis extract into dentin matrix may improve biochemical and biomechanical properties.
  • 61. Enamel matrix derivative (EMD) • Enamel matrix derivative is derived from pig enamel matrix (Emdogain; Straumann AG, Basel, Switzerland) • It has been employed in patients with severe attachment loss through recruitment of cementoblasts on to the root-surface to restore functional periodontal ligament, cementum and alveolar bone.
  • 62. Growth factors • Growth factors are considered as engines that drive wound healing. Platelet derived growth factor (PDGF) plays key role in chemotaxis of neutrophils that acts with other growth factors to produce collagen. • Keratinocyte growth factor (KGF) through keratinocyte differentiation, plays vital role in wound re-epithelialization. • Transforming growth factor (TGF) induces extracellular matrix deposition and collagen formation.
  • 63. • Fibroblast growth factor (FGF) plays role in fibroblast proliferation, angiogenesis, and matrix deposition. • Vascular endothelial growth factor (VEGF) increases vascular permeability at the capillary level. • Epidermal growth factors (EGF) acts in an autocrine fashion. • Kepivance (KGF-2) is used in preventing oral mucositis. Juvista, a recombinant TGF-b3 may be used as a growth factor enhancer for all surgically created wounds
  • 64. Bone Morphgenic Proteins (BMP) • BMP plays a key role in dental bone grafting and implant placement, fracture healing and spinal fusion. • It increases alkaline phosphatase activity, stimulates proteoglycan synthesis in chondroblasts, collagen synthesis in osteoblasts, differentiation of neural cells and chemo taxis of monocytes.
  • 65. Platelet Concentrates • It was first described by Whitman et all. • Platelet rich plasma (PRP) is generated by differential centrifugation and serves as reservoir of critical growth factors such as platelet- derived growth factor (PDGF), transforming growth factor-b (TGF-B) and insulin-like growth factor-1 (IGF-1) , thus regulates wound-healing. • PRP requires biochemical blood handling with addition of anticoagulants while platelet rich fibrin (PRF) does not. • A second generation platelet concentrate, Leucocyte and platelet rich fibrin (L-PRF) was developed by Choukroun et al in France does not contain any anticoagulant or gellifying agents.
  • 66. Polyhedral Oligomeric Silsesquioxanes (POSS) • Biomaterials such as polyhedral oligomeric silsesquioxanes (POSS) and polyhedral oligomeric silicates (POS) may be fabricated by the incorporation of POSS molecules to provide a nanoscopic topology which favors cellular modulation, bioavailability and differentiation. • Advent of POSS has led to formulation of dental adhesives and composites with improved mechanical and physical properties.
  • 67. Metallic Biomaterials • Metallic biomaterials are mainly used for fabrication of medical devices for hard tissue replacement such as artificial hip joints, bone plates and dental implants. • Stainless steel, cobalt alloys, pure Ti and Ti-6al-4v are mainly used for biomedical applications.
  • 68. Implant Biomaterials/Biomimetic Coatings on Implants • It includes metals and metallic alloys, ceramics, natural materials and synthetic polymers. • Metals and metallic alloys include titanium, tantalum and alloy of Ti-Al-Va, Co-Cr-Mb, Fe- Cr-Ni. Devices made from zirconium, hafnium and tungsten have been evaluated recently. • Hydroxyapatite-coated metal’s coating is done using robotic techniques for osteoconductivity.
  • 69. Polymers • Polymers like polymethylmethacrylate (PMMA), polyethylene (PE), polyurethanes are used in dental surgery since decades. • Polyglycolic acid (PGA), polylactide (PLA), polydioxanone (PDS) are mainly used as resorbable bone fixation devices or as suture materials. • For surgical wound repair fibrin glue is used as tissue adhesive. • Alginate can be used as growth factor delivery system.
  • 70. Regenerative endodontics and tissue engineering • Dental regeneration is a process in humans by which specialized dental tissues are replaced by the recruitment, proliferation, migration, and differentiation of dental stem cells. • Stem cells, scaffolds, and growth factors are 3 key elements for tissue regeneration. • Root Canal Revascularization via Blood Clot In the Root canal revascularization via blood clot in apical region, the bioceramic material is placed as mid-root/coronal plug, thereby providing permanent and superior quality seal.
  • 71. • Jung et al. reported that by activation of MAPK pathway biodentine, bioaggregate and MTA causes odontoblastic differentiation and mineralization. • Postnatal stem cell therapy, pulp implantation, scaffold implantation, injectable scaffold delivery, 3-D cell printing and gene therapy are some regenerative approaches.
  • 72. Smart Materials • It is defined as the class of materials that are highly responsive and have the inherent capability to sense and react according to changes in the environment. • They can be classified as active and passive smart materials. • Passive smart materials responds to external change without any external control. • While active smart materials utilizes a feedback loop to enable them to function like a cognitive response through an actuator circuit.
  • 73. A) Smart pressure bandages - Upon exposure to blood, these bandages contracts thereby putting pressure on a wound. B) Smart suture - It ties itself into the Perfect knot and possesses shape memory.
  • 74. C) Hydrogel - It exhibit plastic contraction upon changes in temperature, pH, magnetic or electrical field. D) Smart composites containing amorphous calcium phosphate (ACP)- Inclusion of ACP into composite resin results into release of calcium and phosphorous for an extended period and are thus helpful in caries prevention.
  • 75. • E) Cercon - smart ceramics - It is a metal-free biocompatible life like restoration that has strength to resist crack formation. • The drawbacks of porcelain fused to metal like unsightly dark margins and artificial grey shadows from the underlying metal are no longer a problem with Cercon.
  • 76. Conclusion • Biomimietic materials functions as root canal sealer, filling materials, cements and root and crown repair material and possesses features as like strengthening the root following obturation, good sealing ability, enhanced biocompatibility and antibacterial properties. • Contemporary biomaterials have shown ability to overcome the limitations of traditional materials.
  • 77. • However, there exists limitations when considering criteria for categorizing them as ideal materials. • Several in vitro and in vivo studies have demonstrated good results, however randomized and double blind studies of sufficient duration with biomimetic materials have been needed to confirm long term success.
  • 78. REFRENCES • Cohen's Pathways of the Pulp, 11th Edition • Sonarkar S, Purba R. Bioactive materials in conservative dentistry. Int J Contemp Dent Med Rev. 2015;2015:4. • Madfa AA, Al-Sanabani FA, Al-Kudami NH. Endodontic Repair Filling Materials: A Review Article. • Bhushan M, Tyagi S, Nigam M, Choudhary A, Khurana N, Dwivedi V. Bioactive materials: A short review. J. Orofac. Res. 2015 Oct;5:138-41. • Jefferies S. Bioactive and biomimetic restorative materials: a comprehensive review. Part II. Journal of Esthetic and Restorative Dentistry. 2014 Jan 1;26(1):27-39.

Notes de l'éditeur

  1. A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase).