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One step to forward- Biomaterials
Dr. Kyaw Tint
Associate Professor
Department of Prosthodontics
University of Dental Medicine, Yangon
Today presentation includes
• Introduction….
• Bone Substitute
• Membrane- Resorbable &Non-resorbable
• Titanium- Fixture, Mesh
• Zarconium
• Nanotechnology- General, Clinical
Biomaterial
• Definition -material exploited in contact with
living tissues, organisms,or microorganisms
- can be derived either from nature or
- synthesized in the laboratory
- using a variety of chemical approaches
- utilizing metallic components, polymers,
ceramics or composite materials
• Ideally, a biomaterial
- should be non-toxic, non-irritant, have no
carcinogenic or allergic potential and,
- if used as a filling material, should be
harmless to the pulp
Scope
• The field of biomaterials science encompasses
all classes of material, i.e. polymers, ceramics,
glasses and metals,
• and a wide range of branches of surgery:
dental, ophthalmic, orthopaedic, cardiovascular
and so on.
Biomaterials are used in:
• Joint replacements
• Bone plates
• Bone cement
• Artificial ligaments and tendons
• Dental implants for tooth fixation
• Blood vessel prostheses
• Heart valves
• Skin repair devices (artificial tissue)
• Cochlear replacements
• Contact lenses
• Breast implants
• Drug delivery mechanisms
• Sustainable materials
• Vascular grafts
• Stents
• Nerve conduits
• Surgical sutures, clips, and staples for wound
closure
Biocompatibility
• Biocompatibility is related to the behavior of
biomaterials in various environments under
various chemical and physical conditions.
• For example, a material may elicit little or no
immune response in a given organism, and
may or may not able to integrate with a
particular cell or tissue.
Biocompatibility
• not a property of a material per se; the
material needs to elicit an appropriate
response,
• distinct from that of inertness, which would
imply a complete absence of response from
the body (e.g GP points)
Biopolymers
• Produced by living organisms.
• e.g- Cellulose and starch, proteins and peptides,
and DNA and RNA in which the monomeric units,
respectively, are sugars, amino acids, and
nucleotides.
Biomaterial as scaffold
• When the damage is so extreme that it is
impossible to use the patient’s own cells,
artificial tissue cells are grown. The difficulty is
in finding a scaffold that the cells can grow and
organize on.
• The characteristics of the scaffold must be that
it is biocompatible, cells can adhere to the
scaffold, mechanically strong and
biodegradable.
Bone Substitutes
• collagen is the building block of the organic
matrix—a triple helix with diameter of 1.5 nm.
• the hydroxyapatite crystals are platelets that
have a diameter of approximately 70– 100 nm
and thickness of 1 nm. They originally nucleate
at the gaps between collagen fibrils.
Bone constituents
What are..
• Osseoinduction is the ability to promote de novo
bone formation remote from the host bone even
within noncalcified tissues
• Osseoconduction is the property of promoting bone
growth from the surrounding host bone onto the
surface of the graft material, using the graft as a
framework
Autogenous bone grafts
Availability
Sterility
Biocompatibility
Osseoinductive potential
Osseoconductive potential
Ease of use
Autogenous bone graft
Autogenous bone graft
The ideal characteristics of a
substitute bone graft material
Sterile
Non-toxic
Non-immunogenic
Osteoinductive or osteoconductive
Favorable clinical handling
Resorption and replacement by host bone
Synthetic Available in sufficient quantities
Low in cost
Allograft (Allogenic grafts)
• Bone derived from cadavers
• The graft may be freezedried or decalcified
freeze-dried bone allograft (DFDBA),
• A good source of bone morphogenetic protein
• They are osteoconductive, providing a
framework for new bone growth
• Available in varying thicknesses of 20–700 μm,
Xenograft
Deproteinized bovine bone mineral
• Similar properties to human cancellous bone
• As a purely mineral(Calcium) graft it is
osseoconductive
• Mixed with the patient’s blood and packed
into the defect
• As a filler to increase the volume of
autogenous graft material
Alloplastic graft materials
• no risk of cross-infection
• but may still give rise to an antigenic response
• as a framework for bone formation on their
surface and are therefore osseoconductive
• They include:
- Hydroxyapatite , Calcium Phosphate
- Tricalcium Phosphate (TCP), Bioactive Glasses
- Calcium Carbonate
Alloplast: Bioactive Glass Nanoparticles
• Bioactive glasses were first developed by
Hench et al. in 1969
• in different forms, such as bulk, powder,
composites, and porous scaffolds.
• able to bond to mineralized bone tissue in
physiological environment
Composition and synthesis of
bioactive glass nanoparticles
• The sol-gel-derived bioactive glasses, the
composition of 60% SiO2, 36% CaO, and
4% P2O5 (by weight) has a high level of
bioactivity,
• The synthesis of bioactive glass uses typical
precursors like tetraethyl orthosilicate (TEOS),
calcium nitrate (CN), and triethylphosphate
(TEP).
Bioactive glass in dentistry
• use as bone grafts, implant coatings, bone
cements, toothpaste, and various other
applications in dentistry.
• e.g-Bioglass, Perioglass
• Bioactive glasses are known for
osteoconductivity and bonding to bone
through the release of ions and formation of a
layer of apatite
New alloplast: Bioactive glass + Polymers
• The combination of biodegradable polymers and
bioactive ceramic creates a new type of material
for tissue engineering applications
• Several synthetic or natural polymers, such as
polyvinyl alcohol (PVA), chitosan, polyethylene
glycol (PEG), gelatin, collagen,
poly(caprolactone) (PCL), and polyurethanes, are
used to construct nanocomposites for tissue
engineering applications
Membranes
Non-resorbable membranes for
Guided bone regeneration
• expanded polytetrafluoroethylene (PTFE,
Gore-Tex™)
• requires removal at second-stage surgery
• The creation and maintenance of a volumetric
defect is critical and this may be improved by
reinforcing PTFE membranes with titanium
strips
Non-resorbable membrane
Resorbable membranes for Guided
bone regeneration
• Made of synthetic polymers such as
polylactate and polyglycolic acid, as well as
collagen membranes
• Resorbable materials should be functional for
between 3 and 6 months after insertion
GTR &
GBR
Titanium
• The alpha (α) alloys have a hexagonal closely
packed (hcp) crystallographic structure, while
the beta alloys (β) have a body-centred cubic
(bcc) form
• Aluminium is an alpha-phase stabilizer and
increases the strength of the alloy, while it
decreases its density.
• On the other hand, vanadium is a beta-phase
stabilizer
Efforts to promote osteointegration
It is better to know
Mesenchymal Stem Cells
Origin of mesenchymal stemm
cells
• While originally identified in the bone marrow
• MSCs have been extracted from numerous
tissues including adipose , heart, dental pulp ,
peripheral blood, and cord blood.
• One of the major properties of MSCs is their
ability to differentiate into various cells….
• like adipocytes , chondrocytes, osteoblasts ,
neurons, muscles , and hepatocytes in vitro
after treatment with induction agents
Migration, adhesion, and proliferation
• stimulated in vitro by many growth factors
including Platelet-derived growth factor
(PDGF) , Epidermal growth factor (EGF) ,
Vascular endothelial growth factor (VEGF) ,
Transforming growth factor (TGF-β) , Bone
morphogenetic protein-2 (BMP-2) and BMP-4
• plasma clot serves as storage to fibrin
molecules and release system for a variety of
bioactive factors
Migration, adhesion, and proliferation
• After MSCs recruitment in the injured site,
cells adhere on the local extracellular matrix
as well as on the implant surface beginning an
extensive proliferation in order to build up
new tissue.
Differentiation
• Under the influence of these growth factors,
MSCs switch to osteoblastic cells
• In some cases, implants are encapsulated by
fibrous tissue due to the proliferation and
differentiation of MSCs into fibroblastic cells
Implant failure
from chemical point of view
• titanium implants may adsorb hydrogen from
the biological environment, consequently
becoming more brittle and prone to fracture
• Green et al. suggested that galvanic corrosion
between non-precious metal alloy
restorations supported on titanium implants
might initiate a cytotoxic reaction
Implant fracture
Titanium mesh
Lateral ridge augmentation
with additional cortical
perforation, titanium mesh,
nano-HA bone substitution,
reentry after 6 months,
removal of titanium mesh,
gained alveolar ridge
Zarconia
Zarconia
• Ceramics, particularly the yttrium-stabilized
tetragonal polycrystalline zirconia (Y-TZP),
exhibit improved mechanical properties that
make them suitable substrates for the
fabrication of dental implants
• Yttria- a greyish-white metal resembling the
rare earth elements (Y)- atomic no. 39
Zarconia
• Flexural strength -800 to 1000 Mpa
• Fracture strenth- 512 N versus 410.7 N
• Melting point- > 2370 ´C
• Alloying pure zirconia with stabilizing oxides,
such as CaO, MgO, Y2O3 or CeO2, allows the
retention of the metastable tetragonal
structure at room temperature.
Types of Zirconia Used in Dentistry
(i) Yttrium-Stabilized Tetragonal Zirconia
Polycrystals (3Y-TZP)
(ii) Glass-Infiltrated Zirconia-Toughened
Alumina (ZTA)
(iii)Alumina Toughened Zirconia (ATZ)
Low Temperature Degradation of Zarconia
• Also known as ageing- occurs by a slow
surface transformation of the metastable
tetragonal crystals to the stable monoclinic
structure in the presence of water or water
vapour.
How to prevent ageing of Zarconia
• A decrease in grain size and an increase in
stabilizer content were found to retard the
transformation process. The critical grain size
reported in the literature ranges from 0.2 to 1
Îźm depending on the Y2O3 content
Bending load ---> peri-implant bone resorption--->
crown to implant ratio ---> bending moment 
combined with lateral occlusal loading 
premature implant failure
Failure mode of Zarconia
Failure Mode of Zarconia
Failure mode of Zarconia
• Sharp, deep and thin threads as well as sharp
internal line angles represent areas of stress
concentration that can enhance the likelihood
of crack propagation and implant failure
• A reduced implant diameter of 3.25 mm,
associated with a higher bending moment, has
also been reported by Gahlert et al. to be a
contributing factor for implant fracture during
functional loading
Failure mode of Zarconia
• During surgical procedures, difficulties can be
encountered when inserting the implants in
dense hard-type bone.
• If hand torqueing is needed for final insertion
of the implant and the applied forces are not
purely rotational in nature, bending forces
may be generated, resulting in implant failure
Osseointegration of Y-TZP versus
Titanium Dental Implants
• the mean bone-implant contact was above
60%, indicating successful osseointegration
• zirconia implants undergo osseointegration
similar to or even better than that of titanium
implants
• titanium implants were found to have a higher
removal torque resistance, probably due to
the difference in the surface roughness
Modifications to Zarconia
• UV treatment of zirconia - significant decrease in
carbon content and conversion of the surface from
hydrophobic to hydrophilic status
• Coating the surface of Y-TZP implants with bioactive
glass was also reported to accelerate bone healing
and to improve the osseointegration process
Peri-Implant Soft Tissues
• zirconia implants and abutments provide a
very good peri-implant soft tissue interface
that achieves an irritation-free attachment
• The zirconium oxide surfaces showed a
significant reduction in bacterial adhesion
when compared to the titanium specimens
Clinical Studies, Case Reports and Case
Series on Zirconia Implants
• survival rate of 74%–98% after 12–56 months
• success rates between 79.6% and 91.6% after
6–12 months of prosthetic restoration
• However, the urgent need for well-
conducted, long-term, randomized controlled
trials to establish an evidence-based use of
zirconia implants
• Using rapid prototyping technology, a 3D
custom-made layered structure can be
constructed through computer-controlled
extrusion of colloidal pastes, slurries or inks .
• The benefit of this technique over the
conventional milling method is that it is more
economical with minimal material wastage
Nanotechnology
A: Definition & Histroy
Nanotechnology
• “Nano” is derived from the Greek word for “dwarf.”
• American Physicist and Nobel Laureate Dr. Richard
Phillips Feynman who presented
• a paper called “There is plenty of room at the
bottom” in December 29, 1959, at the annual
meeting of the American Physical Society at
California Institute of Technology
History of nanotechnology
In 1959 Richrad Feynman
presented ideas for creating
Nano scale machines
Norio Taniguchi
introduced the term
‘nanotechnology’
1980s, development in this field was
greatly enhanced with advances in
electron microscopy
A nanometer is
• one billionth of a meter, or 3 to 5 atoms in
width.
• 40,000 nanometers lined up in a row to equal
the width of a human hair.
• Nanotechnology can be approached in two
ways: “top-down” and “bottom-up”
approaches
Approaches in nanotechnology
Top-down Approach
Creating Nano-scale materials
by physically or chemically
breaking down larger materials
Bottom-up Approach
Assembling Nano materials
atom-by-atom or molecule-by
molecule (self assembling)
Top-down Bottom-up
Method miniaturization agglomeration
From macroscopic Atoms or
molecules
To Micro/nanoscale Macromolecular
Tech Machining/etching Self-organize/
self-assemble
e.g Semi-conductor
Cochlear
replacements
polymer
Two ways approaches
Dip-pen nanolithography ( DPN)
B:Type of Nanomaterials
Three general categories of nanoparticles
(i) environmental, such as those generated from
forest fires and volcanoes,
(ii) nonengineered, by-products of human activity
(iii) engineered, such as those being developed for
diagnostic imaging and as vehicles for drug delivery
Engineered nanomaterials
• five general types:
(i) carbon-based
(ii) metal-based metal oxides
(iii) semiconductor nanocrystal- quantum dots
(iv) dendrimers, three-dimensional polymer
(v) silica-based,
Carbon
nanotubes
(sensors, fuel cells,
computers
and televisions)
Nano membrane
filtration systems
(safe, clean,
The average size of silver nanoparticles is
approximately 50-80 nm.
Molecularelectronic
‘cross barlatches’
(tiny Nano devices)
Quantum
dots and
artificial atoms
(small devices that
Carbon nanotubes dendrimers
Why we use this tech
• After decreasing material size into the nanoscale,
dramatically increased surface area, surface
roughness, and surface-area-to-volume ratios
• to lead to superior physiochemical properties
(i.e., mechanical, electrical, optical, catalytic, and
magnetic properties).
• Resulting --Quantum size effect- electronic
properties of solids are altered (attractive Vander
Waals forces
Carbon nanotube
Carbon
nanotubes
(sensors, fuel cells,
computers
and televisions)
Nano membrane
filtration systems
(safe, clean,
Carbon-nanotube
• A number of biological molecules can be
incorporate into electrospun fibers-
• natural fibers such as chitosan, collagen, silk,
hyaluronic acid, gelatin, fibrinogen have been
electrospun into fibers.
Effect: immobilization of bacteria
as carriers for drug and
as controlled release agent
Electrospinning in cabon nanotube
Layer-by-layer assembly
• immersing a negatively (or positively) charged
substrate in an oppositely charged
polyelectrolyte which is adsorbed onto the
substrate ( Electrodeposition)
• After equilibrium is reached, the substrate is
removed, rinsed, dried, and immersed in a
negatively charged polyelectrolyte solution.
• This process is repeated until the desired
thickness is achieved.
Cabon-nanotube
• Two important criteria – interfacial adhesion
between the CNT and the polymeric matrix,
and a homogeneous dispersion of CNT in the
matrix
CNT cytotoxicity
• Most of the as-produced CNTs contain
substantial amounts of impurities such as metal
catalyst (Co, Fe, Ni, Mo, and Pt).
• Some of the metals (Co, Ni, Co21) cause
cytotoxic or genotoxic effects as well as lung
diseases including fibrosis and asthma
Purification for CNT
• Several techniques have been used to purify
the as-processed nanotubes.
• These include
- acid treatment ,
- thermal oxidation ,
- acid treatment with thermal oxidation ,
- combination of ultrasonication and
centrifugation using organic solvents
Carbon nanotube in Dentistry
• SWNT- single walled carbon nanotube (< 189nm)
• MWNT- multi walled carbon nanotube (220-825nm)
• Higher degree of sidewall functionalization leads to
reduced cytotoxicity.
• Functionalized CNTs can cross the cell membrane and
accumulate in the cytoplasm without being toxic to cells
• Application to
- dental restoration materials,
- bony defect replacement therapy,
- protein, gene, and drug delivery and cancer
treatment.
Carbon nanotube in Dentistry
CNT applications in restorative dentistry
• Functionalized SWNT has been applied to the
dental composite to increase its tensile
strength and Young’s modulus to help
improve the longevity of composite
restoration in oral cavity
• Also can reduce the chance of secondary
decay development in the long term by
providing protection against decay inducing
bacteria and initiating HA nucleation on its
surface
CNT in bony defect replacement therapy
• Nanoscale HA was formed on the surface of MWNT
when immersed in calcium phosphate solution of 37´C
for 2 weeks
• A biomembrane by electronspinning a suspension of
poly (L-lactic acid) (PLLA), MWNT and HA to promote
guided bone regeneration
• A new chitosanMWNT composite has been developed
which can promote osteoblast proliferation and apatite
crystal formation on the surface of MWNT while
discouraging adhesion of fibroblast
Metal Nanoparticles
As antimicrobial agents
• Copper oxide (CuO and Cu2O)
• Zinc Oxide (ZnO)
• Titanium dioxide (TiO2)
---Semi-conducting, simplest member, high
temperature superconductivity, high electron
correlation effect, spin dynamics and cheap
Synthesis of fluorescent metal core-shell nanoparticles
Cobalt
Ferrite
CuO nanoparticles
• generated by thermal plasma technology,
• particle sizes -range 20-95 nm with a mean surface
area of 15.7 m2/g
• In suspension showed activity against a range of
bacterial pathogens, including
• MRSA , E. coli,
(MRSA)-methicillin-resistant Staphylococcus aureus
Titanium Oxides
• particle size in 18 nm; surface area: 87 m2
/g
• have a growth inhibitory and killing effect
against E. coli and MRSA have been shown to
be 1.0-2.5 and >2.5 mg/mL
Treatment of oral cancer using
nanoparticulate drug delivery system
• A single dendrimer can carry an anticancer
drug molecule that recognizes cancer cells, a
therapeutic agent to kill those cells.
Silica based nanoparticles
Silica nanoparticles
• Silica is an oxide of silicon ( silicon dioxide, SiO2)
• Silica in the form of orthosilicic acid is the form
predominantly absorbed by humans and is
found in numerous tissues including bone,
tendons, aorta, liver, and kidney
Synthesis of silica-based
nanomaterials
Pyrogenic- combusting or heating
modification of silica to use in dentistry
- addition of Îł- methacryl-oxypropyl-trimethoxy-
silane (Îł-MPS) to silica-based nanomaterials
used to improve adhesion of the nanoparticles
within the resin matrix, as well as to reduce
agglomeration
Skeletal applications of silica-based
nanomaterials
• Osteoblasts grown on silica-coated disks
demonstrated increased hydroxyapatite
formation although alkaline phosphatase and
cell number was not changed
• Silica has also been incorporated into
hydroxyapatite/bioceramic artificial bone
scaffolds, where it is reported to enhance
osteoconductivity and proliferation
Skeletal applications of silica-based
nanomaterials
• surprisingly, 50 nm silica nanoparticles have
been detected to cross the bloodbrain barrier
in mice although without apparent negative
effects or toxicity
C:Nano-systems in Clinical Dentistry
Nanosystems with dental applications
Nano & Restorative Dentistry
Process of Tooth Decay ( L= Lactate)
Nanobiomaterials in Restorative
Dentistry
• Dental nanocomposites- silicon dioxide
• Silver nanoparticles – anti-bact:, fungal, viral
• Nanocomposites in bone regeneration
Glass Ionomers, Composite, Adhesive- had
already known in Curicullum
Silver Nanoparticles:
• 1 g of silver has 1.6 x 1022
atoms
• One atom 0.165 nm x 7 atoms= 1 nm
• Silver nanoparticles are known for their broad-
spectrum antimicrobial activity against bacteria,
fungi, and viruses
Future prospective in adhesive dentistry
1. On-demand antibacterial adhisives
2.Improving adhesive polymerization through
catalytic activity of nanoparticles
3.Antibacterial orthodontic adhesives containing
nanosiver
4.Radiopaque dental adhesives
5. Self-adhesive composites
6. Self-healing adhesives
7. High-speed AFM (atomic force microscopy)
Nano & Prevention
Main strategies for implementation of
nanosized materials in
dental prophylaxis
(i) the interaction with bacterial adherence and
oral biofilm formation and
(ii) the impact on de- and remineralization
Nanobiomaterals in Preventive
Dentistry
• formation of the acquired pellicle which
occurs almost instantaneously on all solid
substrates exposed to the oral fluids
• It offers protection against erosive mineral
loss and modulates de- and remineralization
• Longer exposure to beverages or acids at low
pH inevitably leads to destruction of the
pellicle and continuous mineral loss
Nanobiomaterals in Preventive
Dentistry
• the pellicle contains a couple of specific and
unspecific antibacterial and antimicrobial
proteins, glycoproteins, and peptides (such as
secretory immunoglobulin A or lactoferrin) as
well as, and enzymes (such as lysozyme or
peroxidase
• Despite these antibacterial properties, the pioneer
bacteria have adapted to the protective properties
of the pellicle layer
Nanosized calcium fluoride
• Nano-CaF2 powder containing clusters of 10-15
nm sized crystallite particles has been prepared
from Ca(OH)2 and NH4F solutions using a spray
drying technique
• 1-min application of this nano-CaF2 rinse
produces a significantly greater 1-h postrinse
salivary fluoride content (158 Îźmol/L) than a
NaF rinse (36 Îźmol/L)
Nanomaterial in enamel and dentine
remineralization
• nano-HA helped mineral deposition predominantly
in the outer layer of the lesion
• combined GCE( Galla Chinensis) and nano-HA
treatment on promoting the remineralization of
initial enamel lesion
• Nanosized casein phosphopeptide-amorphous
calcium phosphate (CPP-ACP) prevents
demineralization and promotes remineralization of
initial enamel lesions
Nanomaterial in dentin-pulp complex
regeneration
• There is evidence suggesting that odontoblasts
(cells that produce dentin), dental pulp stem cells
(DPSC) and stem cells from human exfoliated
deciduous teeth (SHED) are able to produce
pulp/dentin-like tissues when seeded on specific
condition or scaffolds
• SHED mixed with nanofiber peptide scaffold and
injected into full-length root canals were able to
generate a dental pulp
Dentin hypersensitivity
• a glycerine-enriched gelatine gel containing
phosphate and fluoride ions is as effective as
• the clinically established application of a
glutaraldehyde containing agent (Gluma) in
treatment of patients suffering from dentin
hypersensitivity
Nano & Oral Biofilm
What is biofilm?
• an aggregate of microorganisms in which
• Up to 1000 different species of bacteria at 108
-109
bacteria per milliliter saliva or per milligram dental
plaque
• Depend on oxygen levels and anaerobiosis,
availability of nutrients, exposure to salivary
secretions or gingival crevicular fluid (GCF),
masticatory forces, oral hygiene procedures
What is acquired pellicle?
• Contents-several salivary components such as
secretory immunoglobulin A (sIgA) and
lysozyme,
• Function-
-provide both barrier and buffering functions
-both de- and remineralization processes of
the teeth are also mediated by the pellicle
ACP- Amorphous Calcium Phosphate
CPP- Casein phosphopeptides
Biofilms and oral infections
• Biofilms of oral bacteria and yeasts can cause
a number of localized diseases in the oral
cavity, including dental caries, gingivitis,
periodontitis, candidiasis, endodontic
infections, orthodontic infections, and peri-
implantitis
• (known pathogenesis)
• The nanosized apatite particles adsorbed to
the bacterial surface might interfere with the
bacterial adhesins, which are important for
irreversible binding of bacteria to the tooth
surface
Antiadhesive nanoparticles and oral
biofilm control
• Chitosan nano- and microparticles .
• Silica and silicon nanoparticles
• Hydroxyapatite and other calcium phosphate-
based systems
Chitosan nano- and microparticles
• Chitosan is a biopolymer derived by the
deacetylation of chitin, a natural polymer
occurring in the exoskeleton of crustaceans.
Chitosan is positively charged and soluble in
acidic to neutral solution, enabling it to bind
to mucosal surfaces
• Crustaceans- aquatic arthropods: crabs,
lobsters, shrimps etc.
• (other two mat: had already known)
Nanoparticles and the Control of Oral Biofilms
Nanoparticles and the Control of Oral
Biofilms
Nanoparticles and the Control of Oral
Biofilms
Photodynamic therapy and the use of
nanoparticles to control oral biofilms
• The killing of microorganisms with light
depends upon cytotoxic singlet oxygen
and free-radical generation by the excitation
of a photoactivatable agent or sensitizer
• The photosensitizer erythrosine has an
advantage over other dyes because it is
currently used in dentistry to visualize dental
plaque in vivo, and so its lack of toxicity in the
host
Nano & Orthodontics
Brackets
• The surface characteristics (roughness and
surface free energy (SFE)) of the brackets play
a significant role in reducing friction and
plaque (biofilm) formation.
• Micro- and nanoscale roughness of these
brackets can facilitate early bacterial
adhesion.
AFM image of retrieved NiTi archwire exposed in oral
cavity for 1 month, depicting rough surface produced
by calcification on wire surface
Friction reducing nanocoatings on
orthodontic archwires
• The types of wires most commonly used are
stainless steel, NiTi, and beta-titanium alloy
wires (composed of titanium, molybdenum,
zirconium, and tin)
• Dry lubricants composed by nanoparticles are
solid phase materials that are able to reduce
friction between two surfaces sliding against
each other without the need for a liquid
media.
Friction reducing nanocoatings on
orthodontic archwires
• Inorganic fullerene-like nanoparticles of
tungsten disulfide (IF-WS2) which are potent
dry lubricants reduced up to 54% of frictional
force when compared to uncoated stainless
steel wire
Friction reducing nanocoatings on
orthodontic archwires
• NiTi substrates were coated with cobalt and
IF-WS2 nanoparticles film by electrodeposition
procedure and the friction test results showed
up to 66% reduction of the friction coefficient
on the coated substrates when compared to
uncoated substrates
Studies on Nanoparticle Applications in Materials Used
in Orthodontics
Studies on Nanoparticle Applications in Materials Used
in Orthodontics
SEM of hydroxyapatite (A) and
fluoroapatite (B) nanopowders
Nanoparticle delivery from orthodontic
elastomeric ligatures
• The release of anticariogenic fluoride from
elastomeric ligatures has been reported
• Medicated wax applied to orthodontic
brackets that slowly and continuously
released benzocaine was shown to be
significantly more effective in reducing pain
associated with mucosal irritation caused by
brackets
Future in orthodontics
• The use of shape-memory polymer in
orthodontics
• BioMEMS/NEMS for orthodontic tooth
movement and maxillary expansion
• Nanorobot delivery for oral anesthesia and
improved oral hygeine
• Temporary anchorage devices
Applications of
Micro Electromechanical Systems
(MEMS)
Nano Electromechanical Systems
(NEMS)
in Orthodontics
Nano & Prostho:
Denture-induced stomatitis related with
fungal infection on palate and vestibule of
maxilla
Silver Nanoparticles Incorporated
Acrylic-Based Tissue Conditioner
Acrylic-based tissue conditioner
The average size of silver nanoparticles is
approximately 50-80 nm.
In vitro antimicrobial effects on S. aureus,
Streptococcus mutans, and C. albicans
Nano & Dental Implant
Impact of Nanotechnology on Dental Implants
TiO2 nanotubes on Titanium
• TiO2 nanotubes on Ti improved the production of
alkaline phosphatase (ALP) activity by osteoblastic
cells
• Since ALP is a marker of osteogenic
differentiation, these surfaces may demonstrate
enhanced bone tissue-integrative properties
Fabrication of NTs on Ti
• The NTs are generally fabricated in the
aqueous hydrofluoric acid (HF) electrolyte in a
two-electrode electrochemical cell at a
constant potential between 5 and 35 V
Nano & Perio
Nanotechnology for periodontal
regeneration
• Yang et al. developed an electrospun nano-
apatite/PCL composite membrane for
GTR/GBR application,
• the results showed that the electrospun
membrane incorporating nanoapatite is
strong, enhances bioactivity and supports
osteoblast-like cell proliferation and
differentiation
Nanotechnology for periodontal
regeneration
• Alginate/nano bioactive glass ceramic (nBGC)
(synthesis of nBGC particles) composite scaffolds
were successfully fabricated using lyophilization
technique and characterized
• The composite scaffolds had a pore size of about
100-300 Îźm
Periodontal ligament cells on scaffold
Confocal laser microscope images of PDLCs on PLLA
(poly L-lactic acid), PLLA/HA, and PLLA/MWNTs/HA
membranes
Surface calcium mapping using EDS(Energy
Dispersive Spectroscopy) on substrates
with cells 4 weeks after cell plating
Bioactive Glass Nanoparticles for
Periodontal Regeneration and
Applications in Dentistry
• Bioactive glasses were first developed by
Hench et al. in 1969
• in different forms, such as bulk, powder,
composites, and porous scaffolds.
• able to bond to mineralized bone tissue in
physiological environment
Composition and synthesis of
bioactive glass nanoparticles
• The sol-gel-derived bioactive glasses, the
composition of 60% SiO2, 36% CaO, and
4% P2O5 (by weight) has a high level of
bioactivity,
• The synthesis of bioactive glass uses typical
precursors like tetraethyl orthosilicate (TEOS),
calcium nitrate (CN), and triethylphosphate
(TEP).
Bioactive glass in dentistry
• use as bone grafts, implant coatings, bone
cements, toothpaste, and various other
applications in dentistry.
• e.g-Bioglass, Perioglass
• Bioactive glasses are known for
osteoconductivity and bonding to bone
through the release of ions and formation of a
layer of apatite
BG: which type of graft?
• Autogenous-
• Allogenous- genetically different, same
species
e.g- Iliac bone marrow, lyophilized bone graft,
freeze-dried bone allograft(FDBA), decalcified
FDBA..
• Heterogenous- both gene and species
different.
• Alloplast- synthetics- e.g bioactive glass
Nanoparticles administered in
Periodontal pockets
• Cell therapy for periodontal regeneration is
new option
• Periodontal ligament cells in direct contact
with bioactive glass nanoparticles exhibited
increased proliferation and cell viability and
also an increase in alkaline phosphatase
activity
Treatment of Dentinal Hypersensitivity
Bioactive glass nanocomposite applications
in bone regeneration and dental implants
• Peter et al. (2010) developed chitosan-
gelatin/bioactive glass nanoparticles
composite scaffolds
• Sowmya et al. (2011) synthesized and
characterized β-chitin hydrogel/bioactive glass
nanoparticles nanocomposite scaffolds for
periodontal regeneration
• Jurczyk et al. (2011) synthesized and
characterized nanocomposite Ti/45S5 Bioglass
for use in dental implants
The future of bioactive glass nanoparticles
• injectable systems containing bioactive glass
nanoparticles (the hydrogel polymer systems) have
many advantages:
(i) They have adequate permeability for the transport
of cell nutrients and metabolites,
(ii) they exhibit biocompatibility and biodegradability,
and
(iii) some formulations are thermoresponsive
The future of bioactive glass nanoparticles
• Bioactive glasses have ideal characteristics for drug
delivery systems; they can carry an active dose of drug
molecules to target sites without any leak and
premature negative effect on other areas.
• An indication of use of these systems in dentistry is
the treatment of head and neck tumors that needs
controlled release of drugs at specific sites
cells removed from the periodontal tissue,
expanded and injected into the injured tissue.
Nano & Endo
Scope of Nanotechnology in
Endodontics
• Clinical applications
Instrument
Canal disinfection- Irrigants, Medicaments,
Material – Obturating, sealers, retro-filling
• Repair and pulp regeneration
Instrument modifications
• Adini et al. examined the effects of cobalt
coatings with impregnated fullerene-like WS2
nanoparticles on file fatigue and failure of NiTi
files
• In another study, the distal end of the file was
modified by selective coating of endodontic
files
Enhancement of canal disinfection
• Irrigants- nanoparticle-based antimicrobial
photodynamic therapy
• e.g. poly(lactic-co-glycolic acid) (PLGA)
nanoparticles loaded with the photosensitizer
methylene blue (MB) and light against Enterococcus
faecalis by transmission electron microscopy (TEM)
• The synergism of light and MB-loaded nanoparticles
led to approximately 2 and 1 log 10 reduction of
colony-forming units (CFUs) in planktonic phase and
root canals, respectively
Medicaments
• Nanoparticulates such as chitosan (CS-np) and
zinc oxide (ZnO-np) have been shown to possess
significant antibacterial properties ( a significant
reduction in the thickness of Biofilm)
Modifications on- Obturating materials
• Bioactive glass 45S5 is one of the recent
nanoparticles used in endodontic therapy. It has
amorphous nanoparticles of 20-60 nm in size.
• nanohydroxyapatite crystals in 279 nm showed
superior antimicrobial activity (Actinomyces
naeslundii, Peptostreptococcus anaerobius,
Porphyromonas gingivalis, Porphyromonas
endodontalis, and Fusobacterium nucleatum) as
well as minimal microleakage.
• nanocrystalline tetracalcium phosphate had
significantly higher antimicrobial potency in an
agar-diffusion test
Modifications on- Sealers
Retro-filling and root-repair materials
• Mineral Trioxide Aggregate (MTA) has become
the material of choice of retrograde filling
Factors influencing the bioactivity of
the NTs
• Sterilization
• Cell phenotype
• Protein concentration
• Protein distribution pattern
Nano & OMFS
Nanoceramics for Bone Regeneration
in the Oral and Craniomaxillofacial Complex
Nanoceramics and bone repair
• porous hydroxyapatite (HA) and tricalcium
phosphate (TCP) have been shown to have
excellent osteoconductive properties, but
their biodegradation is poor
• HA: nanometer-sized needlelike crystals of
approximately 5-20 nm width by 60 nm length
• nanOsss bone void filler, Ostims
Nanomaterials is superior to conventional mat: for
bone regeneration
Nanotechnology for craniofacial bone
and cartilage tissue engineering
Nanotechnology for craniofacial bone and
cartilage tissue engineering
• Due to the biomimetic features and excellent
physicochemical properties, nanomaterials
have been shown to improve adhesion,
proliferation, and differentiation of cells,
which would finally guide tissue regeneration
• Synthetic and natural polymers are excellent
candidates for bone/cartilage tissue
engineering application due to their
biodegradability and ease of fabrication
Nano & Oral Medicine
Nanoparticles preparation
methods
Saliva- our friend
Saliva as a biofluid for disease detection
Saliva as a biofluid for disease detection
Saliva as a biofluid for disease detection
Applications of
Micro Electromechanical Systems
(MEMS)
Nano Electromechanical Systems
(NEMS)
in salivary diagnostics
Nanorogel & Nanorobot
Nanogel for Local Anaethesia
• Nanogels are probably one of the best
candidates due to the lesser pain during
injection and longer blood circulation time.
• Tan et al. reported the nanogel systems for LAs
such as bupivacaine poly(DL-lactide-co-
glycolide) nanospheres, procaine hydrochloride
(PrHy) hydrogel delivery systems and showed
that the drug release can be delayed over 7-15
h
Nanorobots -Curing the hypersensitivity
• Microscopic studies reported earlier show
that when dentin is exposed for 5 min to fluids
like red and white wine, citrus fruit juices,
apple juice, and yogurt, they remove the
smear layer and open up dentinal tubules
• the construction of reconstructive dental
nanorobots, using native biological materials,
could selectively and precisely occlude specific
tubules within minutes, offering patients a
quick and permanent cure
Nanorobotic dentifrices
• a caries vaccine may be available in near future
• Dentifrice robots would also provide a
continuous barrier to halitosis, since bacterial
putrefaction is the central metabolic process
involved in oral malodor
• Artificial phagocytes called microbivores could
patrol the bloodstream, seeking out and
digesting unwanted pathogens including
bacteria, viruses, or fungi
Challenges of biomaterials
• The successful use of biomaterials presents
numerous challenges. A major one is the issue of
maintenance, and in particular that most devices
are implanted well into the body and therefore
not freely available for inspection or repair
• Life expectancy in the wealthier parts of the
world is now of the order of 80 years, which
means that many people now outlive (overstay)
the useful life of their own connective tissue
Toxicity of nanoparticles
1. Cytotoxicity of one or more of the
nanoparticle constituents which is an inherent
property of the chemical compound
2. Cytotoxicity of one or more of the
degradation products of the nanoparticle
constituents
3. Endocytosed nanoparticle-mediated
apoptosis (cell death)
4. Nanoparticle-mediated cell membrane lysis
Nanoparticle Cytotoxicity to Mammalian
Cells
References
1. Chemistry of Medical and Dental Material by
John W. Nicholson (2002)
2. Dental biomaterials- Imaging, testing and
modelling by Richard Curtis (2008)
3. Nanobiomaterials in Clinical Dentistry by
Karthikeyan Subramani (2013)
4. Advanced Biomaterials and biodevices by
Ashutosh Tiwari ( 2014)
Thanks for your kind attention

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Bone Substitute and Membrane Advances in Biomaterials

  • 1. One step to forward- Biomaterials Dr. Kyaw Tint Associate Professor Department of Prosthodontics University of Dental Medicine, Yangon
  • 2. Today presentation includes • Introduction…. • Bone Substitute • Membrane- Resorbable &Non-resorbable • Titanium- Fixture, Mesh • Zarconium • Nanotechnology- General, Clinical
  • 3. Biomaterial • Definition -material exploited in contact with living tissues, organisms,or microorganisms - can be derived either from nature or - synthesized in the laboratory - using a variety of chemical approaches - utilizing metallic components, polymers, ceramics or composite materials
  • 4. • Ideally, a biomaterial - should be non-toxic, non-irritant, have no carcinogenic or allergic potential and, - if used as a filling material, should be harmless to the pulp
  • 5. Scope • The field of biomaterials science encompasses all classes of material, i.e. polymers, ceramics, glasses and metals, • and a wide range of branches of surgery: dental, ophthalmic, orthopaedic, cardiovascular and so on.
  • 6. Biomaterials are used in: • Joint replacements • Bone plates • Bone cement • Artificial ligaments and tendons • Dental implants for tooth fixation • Blood vessel prostheses • Heart valves • Skin repair devices (artificial tissue) • Cochlear replacements
  • 7. • Contact lenses • Breast implants • Drug delivery mechanisms • Sustainable materials • Vascular grafts • Stents • Nerve conduits • Surgical sutures, clips, and staples for wound closure
  • 8. Biocompatibility • Biocompatibility is related to the behavior of biomaterials in various environments under various chemical and physical conditions. • For example, a material may elicit little or no immune response in a given organism, and may or may not able to integrate with a particular cell or tissue.
  • 9. Biocompatibility • not a property of a material per se; the material needs to elicit an appropriate response, • distinct from that of inertness, which would imply a complete absence of response from the body (e.g GP points)
  • 10. Biopolymers • Produced by living organisms. • e.g- Cellulose and starch, proteins and peptides, and DNA and RNA in which the monomeric units, respectively, are sugars, amino acids, and nucleotides.
  • 11. Biomaterial as scaffold • When the damage is so extreme that it is impossible to use the patient’s own cells, artificial tissue cells are grown. The difficulty is in finding a scaffold that the cells can grow and organize on. • The characteristics of the scaffold must be that it is biocompatible, cells can adhere to the scaffold, mechanically strong and biodegradable.
  • 13. • collagen is the building block of the organic matrix—a triple helix with diameter of 1.5 nm. • the hydroxyapatite crystals are platelets that have a diameter of approximately 70– 100 nm and thickness of 1 nm. They originally nucleate at the gaps between collagen fibrils. Bone constituents
  • 14. What are.. • Osseoinduction is the ability to promote de novo bone formation remote from the host bone even within noncalcified tissues • Osseoconduction is the property of promoting bone growth from the surrounding host bone onto the surface of the graft material, using the graft as a framework
  • 15. Autogenous bone grafts Availability Sterility Biocompatibility Osseoinductive potential Osseoconductive potential Ease of use
  • 18. The ideal characteristics of a substitute bone graft material Sterile Non-toxic Non-immunogenic Osteoinductive or osteoconductive Favorable clinical handling Resorption and replacement by host bone Synthetic Available in sufficient quantities Low in cost
  • 19. Allograft (Allogenic grafts) • Bone derived from cadavers • The graft may be freezedried or decalcified freeze-dried bone allograft (DFDBA), • A good source of bone morphogenetic protein • They are osteoconductive, providing a framework for new bone growth • Available in varying thicknesses of 20–700 Îźm,
  • 20. Xenograft Deproteinized bovine bone mineral • Similar properties to human cancellous bone • As a purely mineral(Calcium) graft it is osseoconductive • Mixed with the patient’s blood and packed into the defect • As a filler to increase the volume of autogenous graft material
  • 21. Alloplastic graft materials • no risk of cross-infection • but may still give rise to an antigenic response • as a framework for bone formation on their surface and are therefore osseoconductive • They include: - Hydroxyapatite , Calcium Phosphate - Tricalcium Phosphate (TCP), Bioactive Glasses - Calcium Carbonate
  • 22.
  • 23.
  • 24. Alloplast: Bioactive Glass Nanoparticles • Bioactive glasses were first developed by Hench et al. in 1969 • in different forms, such as bulk, powder, composites, and porous scaffolds. • able to bond to mineralized bone tissue in physiological environment
  • 25.
  • 26. Composition and synthesis of bioactive glass nanoparticles • The sol-gel-derived bioactive glasses, the composition of 60% SiO2, 36% CaO, and 4% P2O5 (by weight) has a high level of bioactivity, • The synthesis of bioactive glass uses typical precursors like tetraethyl orthosilicate (TEOS), calcium nitrate (CN), and triethylphosphate (TEP).
  • 27. Bioactive glass in dentistry • use as bone grafts, implant coatings, bone cements, toothpaste, and various other applications in dentistry. • e.g-Bioglass, Perioglass • Bioactive glasses are known for osteoconductivity and bonding to bone through the release of ions and formation of a layer of apatite
  • 28. New alloplast: Bioactive glass + Polymers • The combination of biodegradable polymers and bioactive ceramic creates a new type of material for tissue engineering applications • Several synthetic or natural polymers, such as polyvinyl alcohol (PVA), chitosan, polyethylene glycol (PEG), gelatin, collagen, poly(caprolactone) (PCL), and polyurethanes, are used to construct nanocomposites for tissue engineering applications
  • 30.
  • 31. Non-resorbable membranes for Guided bone regeneration • expanded polytetrafluoroethylene (PTFE, Gore-Tex™) • requires removal at second-stage surgery • The creation and maintenance of a volumetric defect is critical and this may be improved by reinforcing PTFE membranes with titanium strips
  • 33. Resorbable membranes for Guided bone regeneration • Made of synthetic polymers such as polylactate and polyglycolic acid, as well as collagen membranes • Resorbable materials should be functional for between 3 and 6 months after insertion
  • 34.
  • 37.
  • 38.
  • 39. • The alpha (Îą) alloys have a hexagonal closely packed (hcp) crystallographic structure, while the beta alloys (β) have a body-centred cubic (bcc) form • Aluminium is an alpha-phase stabilizer and increases the strength of the alloy, while it decreases its density. • On the other hand, vanadium is a beta-phase stabilizer
  • 40. Efforts to promote osteointegration
  • 41. It is better to know Mesenchymal Stem Cells
  • 42. Origin of mesenchymal stemm cells • While originally identified in the bone marrow • MSCs have been extracted from numerous tissues including adipose , heart, dental pulp , peripheral blood, and cord blood. • One of the major properties of MSCs is their ability to differentiate into various cells…. • like adipocytes , chondrocytes, osteoblasts , neurons, muscles , and hepatocytes in vitro after treatment with induction agents
  • 43. Migration, adhesion, and proliferation • stimulated in vitro by many growth factors including Platelet-derived growth factor (PDGF) , Epidermal growth factor (EGF) , Vascular endothelial growth factor (VEGF) , Transforming growth factor (TGF-β) , Bone morphogenetic protein-2 (BMP-2) and BMP-4 • plasma clot serves as storage to fibrin molecules and release system for a variety of bioactive factors
  • 44. Migration, adhesion, and proliferation • After MSCs recruitment in the injured site, cells adhere on the local extracellular matrix as well as on the implant surface beginning an extensive proliferation in order to build up new tissue.
  • 45.
  • 46. Differentiation • Under the influence of these growth factors, MSCs switch to osteoblastic cells • In some cases, implants are encapsulated by fibrous tissue due to the proliferation and differentiation of MSCs into fibroblastic cells
  • 47. Implant failure from chemical point of view • titanium implants may adsorb hydrogen from the biological environment, consequently becoming more brittle and prone to fracture • Green et al. suggested that galvanic corrosion between non-precious metal alloy restorations supported on titanium implants might initiate a cytotoxic reaction
  • 50. Lateral ridge augmentation with additional cortical perforation, titanium mesh, nano-HA bone substitution, reentry after 6 months, removal of titanium mesh, gained alveolar ridge
  • 51.
  • 53. Zarconia • Ceramics, particularly the yttrium-stabilized tetragonal polycrystalline zirconia (Y-TZP), exhibit improved mechanical properties that make them suitable substrates for the fabrication of dental implants • Yttria- a greyish-white metal resembling the rare earth elements (Y)- atomic no. 39
  • 54. Zarconia • Flexural strength -800 to 1000 Mpa • Fracture strenth- 512 N versus 410.7 N • Melting point- > 2370 áż˝C • Alloying pure zirconia with stabilizing oxides, such as CaO, MgO, Y2O3 or CeO2, allows the retention of the metastable tetragonal structure at room temperature.
  • 55.
  • 56. Types of Zirconia Used in Dentistry (i) Yttrium-Stabilized Tetragonal Zirconia Polycrystals (3Y-TZP) (ii) Glass-Infiltrated Zirconia-Toughened Alumina (ZTA) (iii)Alumina Toughened Zirconia (ATZ)
  • 57. Low Temperature Degradation of Zarconia • Also known as ageing- occurs by a slow surface transformation of the metastable tetragonal crystals to the stable monoclinic structure in the presence of water or water vapour.
  • 58. How to prevent ageing of Zarconia • A decrease in grain size and an increase in stabilizer content were found to retard the transformation process. The critical grain size reported in the literature ranges from 0.2 to 1 Îźm depending on the Y2O3 content
  • 59. Bending load ---> peri-implant bone resorption---> crown to implant ratio ---> bending moment  combined with lateral occlusal loading  premature implant failure Failure mode of Zarconia
  • 60. Failure Mode of Zarconia
  • 61. Failure mode of Zarconia • Sharp, deep and thin threads as well as sharp internal line angles represent areas of stress concentration that can enhance the likelihood of crack propagation and implant failure • A reduced implant diameter of 3.25 mm, associated with a higher bending moment, has also been reported by Gahlert et al. to be a contributing factor for implant fracture during functional loading
  • 62. Failure mode of Zarconia • During surgical procedures, difficulties can be encountered when inserting the implants in dense hard-type bone. • If hand torqueing is needed for final insertion of the implant and the applied forces are not purely rotational in nature, bending forces may be generated, resulting in implant failure
  • 63. Osseointegration of Y-TZP versus Titanium Dental Implants • the mean bone-implant contact was above 60%, indicating successful osseointegration • zirconia implants undergo osseointegration similar to or even better than that of titanium implants • titanium implants were found to have a higher removal torque resistance, probably due to the difference in the surface roughness
  • 64. Modifications to Zarconia • UV treatment of zirconia - significant decrease in carbon content and conversion of the surface from hydrophobic to hydrophilic status • Coating the surface of Y-TZP implants with bioactive glass was also reported to accelerate bone healing and to improve the osseointegration process
  • 65. Peri-Implant Soft Tissues • zirconia implants and abutments provide a very good peri-implant soft tissue interface that achieves an irritation-free attachment • The zirconium oxide surfaces showed a significant reduction in bacterial adhesion when compared to the titanium specimens
  • 66. Clinical Studies, Case Reports and Case Series on Zirconia Implants • survival rate of 74%–98% after 12–56 months • success rates between 79.6% and 91.6% after 6–12 months of prosthetic restoration • However, the urgent need for well- conducted, long-term, randomized controlled trials to establish an evidence-based use of zirconia implants
  • 67. • Using rapid prototyping technology, a 3D custom-made layered structure can be constructed through computer-controlled extrusion of colloidal pastes, slurries or inks . • The benefit of this technique over the conventional milling method is that it is more economical with minimal material wastage
  • 69. A: Definition & Histroy
  • 70. Nanotechnology • “Nano” is derived from the Greek word for “dwarf.” • American Physicist and Nobel Laureate Dr. Richard Phillips Feynman who presented • a paper called “There is plenty of room at the bottom” in December 29, 1959, at the annual meeting of the American Physical Society at California Institute of Technology
  • 71. History of nanotechnology In 1959 Richrad Feynman presented ideas for creating Nano scale machines Norio Taniguchi introduced the term ‘nanotechnology’ 1980s, development in this field was greatly enhanced with advances in electron microscopy
  • 72.
  • 73. A nanometer is • one billionth of a meter, or 3 to 5 atoms in width. • 40,000 nanometers lined up in a row to equal the width of a human hair. • Nanotechnology can be approached in two ways: “top-down” and “bottom-up” approaches
  • 74. Approaches in nanotechnology Top-down Approach Creating Nano-scale materials by physically or chemically breaking down larger materials Bottom-up Approach Assembling Nano materials atom-by-atom or molecule-by molecule (self assembling)
  • 75. Top-down Bottom-up Method miniaturization agglomeration From macroscopic Atoms or molecules To Micro/nanoscale Macromolecular Tech Machining/etching Self-organize/ self-assemble e.g Semi-conductor Cochlear replacements polymer Two ways approaches
  • 78. Three general categories of nanoparticles (i) environmental, such as those generated from forest fires and volcanoes, (ii) nonengineered, by-products of human activity (iii) engineered, such as those being developed for diagnostic imaging and as vehicles for drug delivery
  • 79. Engineered nanomaterials • five general types: (i) carbon-based (ii) metal-based metal oxides (iii) semiconductor nanocrystal- quantum dots (iv) dendrimers, three-dimensional polymer (v) silica-based,
  • 80. Carbon nanotubes (sensors, fuel cells, computers and televisions) Nano membrane filtration systems (safe, clean,
  • 81. The average size of silver nanoparticles is approximately 50-80 nm.
  • 82. Molecularelectronic ‘cross barlatches’ (tiny Nano devices) Quantum dots and artificial atoms (small devices that
  • 84.
  • 85. Why we use this tech • After decreasing material size into the nanoscale, dramatically increased surface area, surface roughness, and surface-area-to-volume ratios • to lead to superior physiochemical properties (i.e., mechanical, electrical, optical, catalytic, and magnetic properties). • Resulting --Quantum size effect- electronic properties of solids are altered (attractive Vander Waals forces
  • 86.
  • 88. Carbon nanotubes (sensors, fuel cells, computers and televisions) Nano membrane filtration systems (safe, clean,
  • 89. Carbon-nanotube • A number of biological molecules can be incorporate into electrospun fibers- • natural fibers such as chitosan, collagen, silk, hyaluronic acid, gelatin, fibrinogen have been electrospun into fibers. Effect: immobilization of bacteria as carriers for drug and as controlled release agent
  • 91. Layer-by-layer assembly • immersing a negatively (or positively) charged substrate in an oppositely charged polyelectrolyte which is adsorbed onto the substrate ( Electrodeposition) • After equilibrium is reached, the substrate is removed, rinsed, dried, and immersed in a negatively charged polyelectrolyte solution. • This process is repeated until the desired thickness is achieved.
  • 92. Cabon-nanotube • Two important criteria – interfacial adhesion between the CNT and the polymeric matrix, and a homogeneous dispersion of CNT in the matrix
  • 93. CNT cytotoxicity • Most of the as-produced CNTs contain substantial amounts of impurities such as metal catalyst (Co, Fe, Ni, Mo, and Pt). • Some of the metals (Co, Ni, Co21) cause cytotoxic or genotoxic effects as well as lung diseases including fibrosis and asthma
  • 94. Purification for CNT • Several techniques have been used to purify the as-processed nanotubes. • These include - acid treatment , - thermal oxidation , - acid treatment with thermal oxidation , - combination of ultrasonication and centrifugation using organic solvents
  • 95. Carbon nanotube in Dentistry • SWNT- single walled carbon nanotube (< 189nm) • MWNT- multi walled carbon nanotube (220-825nm) • Higher degree of sidewall functionalization leads to reduced cytotoxicity. • Functionalized CNTs can cross the cell membrane and accumulate in the cytoplasm without being toxic to cells
  • 96. • Application to - dental restoration materials, - bony defect replacement therapy, - protein, gene, and drug delivery and cancer treatment. Carbon nanotube in Dentistry
  • 97. CNT applications in restorative dentistry • Functionalized SWNT has been applied to the dental composite to increase its tensile strength and Young’s modulus to help improve the longevity of composite restoration in oral cavity • Also can reduce the chance of secondary decay development in the long term by providing protection against decay inducing bacteria and initiating HA nucleation on its surface
  • 98. CNT in bony defect replacement therapy • Nanoscale HA was formed on the surface of MWNT when immersed in calcium phosphate solution of 37áż˝C for 2 weeks • A biomembrane by electronspinning a suspension of poly (L-lactic acid) (PLLA), MWNT and HA to promote guided bone regeneration • A new chitosanMWNT composite has been developed which can promote osteoblast proliferation and apatite crystal formation on the surface of MWNT while discouraging adhesion of fibroblast
  • 100. As antimicrobial agents • Copper oxide (CuO and Cu2O) • Zinc Oxide (ZnO) • Titanium dioxide (TiO2) ---Semi-conducting, simplest member, high temperature superconductivity, high electron correlation effect, spin dynamics and cheap
  • 101. Synthesis of fluorescent metal core-shell nanoparticles Cobalt Ferrite
  • 102. CuO nanoparticles • generated by thermal plasma technology, • particle sizes -range 20-95 nm with a mean surface area of 15.7 m2/g • In suspension showed activity against a range of bacterial pathogens, including • MRSA , E. coli, (MRSA)-methicillin-resistant Staphylococcus aureus
  • 103. Titanium Oxides • particle size in 18 nm; surface area: 87 m2 /g • have a growth inhibitory and killing effect against E. coli and MRSA have been shown to be 1.0-2.5 and >2.5 mg/mL
  • 104. Treatment of oral cancer using nanoparticulate drug delivery system • A single dendrimer can carry an anticancer drug molecule that recognizes cancer cells, a therapeutic agent to kill those cells.
  • 106. Silica nanoparticles • Silica is an oxide of silicon ( silicon dioxide, SiO2) • Silica in the form of orthosilicic acid is the form predominantly absorbed by humans and is found in numerous tissues including bone, tendons, aorta, liver, and kidney
  • 108. modification of silica to use in dentistry - addition of Îł- methacryl-oxypropyl-trimethoxy- silane (Îł-MPS) to silica-based nanomaterials used to improve adhesion of the nanoparticles within the resin matrix, as well as to reduce agglomeration
  • 109.
  • 110.
  • 111.
  • 112. Skeletal applications of silica-based nanomaterials • Osteoblasts grown on silica-coated disks demonstrated increased hydroxyapatite formation although alkaline phosphatase and cell number was not changed • Silica has also been incorporated into hydroxyapatite/bioceramic artificial bone scaffolds, where it is reported to enhance osteoconductivity and proliferation
  • 113. Skeletal applications of silica-based nanomaterials • surprisingly, 50 nm silica nanoparticles have been detected to cross the bloodbrain barrier in mice although without apparent negative effects or toxicity
  • 115. Nanosystems with dental applications
  • 116. Nano & Restorative Dentistry
  • 117. Process of Tooth Decay ( L= Lactate)
  • 118. Nanobiomaterials in Restorative Dentistry • Dental nanocomposites- silicon dioxide • Silver nanoparticles – anti-bact:, fungal, viral • Nanocomposites in bone regeneration Glass Ionomers, Composite, Adhesive- had already known in Curicullum
  • 119. Silver Nanoparticles: • 1 g of silver has 1.6 x 1022 atoms • One atom 0.165 nm x 7 atoms= 1 nm • Silver nanoparticles are known for their broad- spectrum antimicrobial activity against bacteria, fungi, and viruses
  • 120.
  • 121. Future prospective in adhesive dentistry 1. On-demand antibacterial adhisives 2.Improving adhesive polymerization through catalytic activity of nanoparticles 3.Antibacterial orthodontic adhesives containing nanosiver 4.Radiopaque dental adhesives 5. Self-adhesive composites 6. Self-healing adhesives 7. High-speed AFM (atomic force microscopy)
  • 123. Main strategies for implementation of nanosized materials in dental prophylaxis (i) the interaction with bacterial adherence and oral biofilm formation and (ii) the impact on de- and remineralization
  • 124. Nanobiomaterals in Preventive Dentistry • formation of the acquired pellicle which occurs almost instantaneously on all solid substrates exposed to the oral fluids • It offers protection against erosive mineral loss and modulates de- and remineralization • Longer exposure to beverages or acids at low pH inevitably leads to destruction of the pellicle and continuous mineral loss
  • 125. Nanobiomaterals in Preventive Dentistry • the pellicle contains a couple of specific and unspecific antibacterial and antimicrobial proteins, glycoproteins, and peptides (such as secretory immunoglobulin A or lactoferrin) as well as, and enzymes (such as lysozyme or peroxidase • Despite these antibacterial properties, the pioneer bacteria have adapted to the protective properties of the pellicle layer
  • 126. Nanosized calcium fluoride • Nano-CaF2 powder containing clusters of 10-15 nm sized crystallite particles has been prepared from Ca(OH)2 and NH4F solutions using a spray drying technique • 1-min application of this nano-CaF2 rinse produces a significantly greater 1-h postrinse salivary fluoride content (158 Îźmol/L) than a NaF rinse (36 Îźmol/L)
  • 127. Nanomaterial in enamel and dentine remineralization • nano-HA helped mineral deposition predominantly in the outer layer of the lesion • combined GCE( Galla Chinensis) and nano-HA treatment on promoting the remineralization of initial enamel lesion • Nanosized casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) prevents demineralization and promotes remineralization of initial enamel lesions
  • 128. Nanomaterial in dentin-pulp complex regeneration • There is evidence suggesting that odontoblasts (cells that produce dentin), dental pulp stem cells (DPSC) and stem cells from human exfoliated deciduous teeth (SHED) are able to produce pulp/dentin-like tissues when seeded on specific condition or scaffolds • SHED mixed with nanofiber peptide scaffold and injected into full-length root canals were able to generate a dental pulp
  • 129. Dentin hypersensitivity • a glycerine-enriched gelatine gel containing phosphate and fluoride ions is as effective as • the clinically established application of a glutaraldehyde containing agent (Gluma) in treatment of patients suffering from dentin hypersensitivity
  • 130. Nano & Oral Biofilm
  • 131. What is biofilm? • an aggregate of microorganisms in which • Up to 1000 different species of bacteria at 108 -109 bacteria per milliliter saliva or per milligram dental plaque • Depend on oxygen levels and anaerobiosis, availability of nutrients, exposure to salivary secretions or gingival crevicular fluid (GCF), masticatory forces, oral hygiene procedures
  • 132. What is acquired pellicle? • Contents-several salivary components such as secretory immunoglobulin A (sIgA) and lysozyme, • Function- -provide both barrier and buffering functions -both de- and remineralization processes of the teeth are also mediated by the pellicle
  • 133. ACP- Amorphous Calcium Phosphate CPP- Casein phosphopeptides
  • 134. Biofilms and oral infections • Biofilms of oral bacteria and yeasts can cause a number of localized diseases in the oral cavity, including dental caries, gingivitis, periodontitis, candidiasis, endodontic infections, orthodontic infections, and peri- implantitis • (known pathogenesis)
  • 135. • The nanosized apatite particles adsorbed to the bacterial surface might interfere with the bacterial adhesins, which are important for irreversible binding of bacteria to the tooth surface
  • 136. Antiadhesive nanoparticles and oral biofilm control • Chitosan nano- and microparticles . • Silica and silicon nanoparticles • Hydroxyapatite and other calcium phosphate- based systems
  • 137. Chitosan nano- and microparticles • Chitosan is a biopolymer derived by the deacetylation of chitin, a natural polymer occurring in the exoskeleton of crustaceans. Chitosan is positively charged and soluble in acidic to neutral solution, enabling it to bind to mucosal surfaces • Crustaceans- aquatic arthropods: crabs, lobsters, shrimps etc. • (other two mat: had already known)
  • 138. Nanoparticles and the Control of Oral Biofilms
  • 139. Nanoparticles and the Control of Oral Biofilms
  • 140. Nanoparticles and the Control of Oral Biofilms
  • 141. Photodynamic therapy and the use of nanoparticles to control oral biofilms • The killing of microorganisms with light depends upon cytotoxic singlet oxygen and free-radical generation by the excitation of a photoactivatable agent or sensitizer • The photosensitizer erythrosine has an advantage over other dyes because it is currently used in dentistry to visualize dental plaque in vivo, and so its lack of toxicity in the host
  • 143. Brackets • The surface characteristics (roughness and surface free energy (SFE)) of the brackets play a significant role in reducing friction and plaque (biofilm) formation. • Micro- and nanoscale roughness of these brackets can facilitate early bacterial adhesion.
  • 144. AFM image of retrieved NiTi archwire exposed in oral cavity for 1 month, depicting rough surface produced by calcification on wire surface
  • 145. Friction reducing nanocoatings on orthodontic archwires • The types of wires most commonly used are stainless steel, NiTi, and beta-titanium alloy wires (composed of titanium, molybdenum, zirconium, and tin) • Dry lubricants composed by nanoparticles are solid phase materials that are able to reduce friction between two surfaces sliding against each other without the need for a liquid media.
  • 146. Friction reducing nanocoatings on orthodontic archwires • Inorganic fullerene-like nanoparticles of tungsten disulfide (IF-WS2) which are potent dry lubricants reduced up to 54% of frictional force when compared to uncoated stainless steel wire
  • 147. Friction reducing nanocoatings on orthodontic archwires • NiTi substrates were coated with cobalt and IF-WS2 nanoparticles film by electrodeposition procedure and the friction test results showed up to 66% reduction of the friction coefficient on the coated substrates when compared to uncoated substrates
  • 148. Studies on Nanoparticle Applications in Materials Used in Orthodontics
  • 149. Studies on Nanoparticle Applications in Materials Used in Orthodontics
  • 150. SEM of hydroxyapatite (A) and fluoroapatite (B) nanopowders
  • 151. Nanoparticle delivery from orthodontic elastomeric ligatures • The release of anticariogenic fluoride from elastomeric ligatures has been reported • Medicated wax applied to orthodontic brackets that slowly and continuously released benzocaine was shown to be significantly more effective in reducing pain associated with mucosal irritation caused by brackets
  • 152. Future in orthodontics • The use of shape-memory polymer in orthodontics • BioMEMS/NEMS for orthodontic tooth movement and maxillary expansion • Nanorobot delivery for oral anesthesia and improved oral hygeine • Temporary anchorage devices
  • 153. Applications of Micro Electromechanical Systems (MEMS) Nano Electromechanical Systems (NEMS) in Orthodontics
  • 155. Denture-induced stomatitis related with fungal infection on palate and vestibule of maxilla
  • 156. Silver Nanoparticles Incorporated Acrylic-Based Tissue Conditioner Acrylic-based tissue conditioner
  • 157. The average size of silver nanoparticles is approximately 50-80 nm.
  • 158. In vitro antimicrobial effects on S. aureus, Streptococcus mutans, and C. albicans
  • 159. Nano & Dental Implant
  • 160. Impact of Nanotechnology on Dental Implants
  • 161. TiO2 nanotubes on Titanium • TiO2 nanotubes on Ti improved the production of alkaline phosphatase (ALP) activity by osteoblastic cells • Since ALP is a marker of osteogenic differentiation, these surfaces may demonstrate enhanced bone tissue-integrative properties
  • 162. Fabrication of NTs on Ti • The NTs are generally fabricated in the aqueous hydrofluoric acid (HF) electrolyte in a two-electrode electrochemical cell at a constant potential between 5 and 35 V
  • 163.
  • 165. Nanotechnology for periodontal regeneration • Yang et al. developed an electrospun nano- apatite/PCL composite membrane for GTR/GBR application, • the results showed that the electrospun membrane incorporating nanoapatite is strong, enhances bioactivity and supports osteoblast-like cell proliferation and differentiation
  • 166. Nanotechnology for periodontal regeneration • Alginate/nano bioactive glass ceramic (nBGC) (synthesis of nBGC particles) composite scaffolds were successfully fabricated using lyophilization technique and characterized • The composite scaffolds had a pore size of about 100-300 Îźm
  • 167.
  • 168. Periodontal ligament cells on scaffold Confocal laser microscope images of PDLCs on PLLA (poly L-lactic acid), PLLA/HA, and PLLA/MWNTs/HA membranes
  • 169. Surface calcium mapping using EDS(Energy Dispersive Spectroscopy) on substrates with cells 4 weeks after cell plating
  • 170. Bioactive Glass Nanoparticles for Periodontal Regeneration and Applications in Dentistry • Bioactive glasses were first developed by Hench et al. in 1969 • in different forms, such as bulk, powder, composites, and porous scaffolds. • able to bond to mineralized bone tissue in physiological environment
  • 171. Composition and synthesis of bioactive glass nanoparticles • The sol-gel-derived bioactive glasses, the composition of 60% SiO2, 36% CaO, and 4% P2O5 (by weight) has a high level of bioactivity, • The synthesis of bioactive glass uses typical precursors like tetraethyl orthosilicate (TEOS), calcium nitrate (CN), and triethylphosphate (TEP).
  • 172.
  • 173. Bioactive glass in dentistry • use as bone grafts, implant coatings, bone cements, toothpaste, and various other applications in dentistry. • e.g-Bioglass, Perioglass • Bioactive glasses are known for osteoconductivity and bonding to bone through the release of ions and formation of a layer of apatite
  • 174. BG: which type of graft? • Autogenous- • Allogenous- genetically different, same species e.g- Iliac bone marrow, lyophilized bone graft, freeze-dried bone allograft(FDBA), decalcified FDBA.. • Heterogenous- both gene and species different. • Alloplast- synthetics- e.g bioactive glass
  • 176. • Cell therapy for periodontal regeneration is new option • Periodontal ligament cells in direct contact with bioactive glass nanoparticles exhibited increased proliferation and cell viability and also an increase in alkaline phosphatase activity
  • 177.
  • 178. Treatment of Dentinal Hypersensitivity
  • 179. Bioactive glass nanocomposite applications in bone regeneration and dental implants • Peter et al. (2010) developed chitosan- gelatin/bioactive glass nanoparticles composite scaffolds • Sowmya et al. (2011) synthesized and characterized β-chitin hydrogel/bioactive glass nanoparticles nanocomposite scaffolds for periodontal regeneration • Jurczyk et al. (2011) synthesized and characterized nanocomposite Ti/45S5 Bioglass for use in dental implants
  • 180. The future of bioactive glass nanoparticles • injectable systems containing bioactive glass nanoparticles (the hydrogel polymer systems) have many advantages: (i) They have adequate permeability for the transport of cell nutrients and metabolites, (ii) they exhibit biocompatibility and biodegradability, and (iii) some formulations are thermoresponsive
  • 181. The future of bioactive glass nanoparticles • Bioactive glasses have ideal characteristics for drug delivery systems; they can carry an active dose of drug molecules to target sites without any leak and premature negative effect on other areas. • An indication of use of these systems in dentistry is the treatment of head and neck tumors that needs controlled release of drugs at specific sites
  • 182. cells removed from the periodontal tissue, expanded and injected into the injured tissue.
  • 184. Scope of Nanotechnology in Endodontics • Clinical applications Instrument Canal disinfection- Irrigants, Medicaments, Material – Obturating, sealers, retro-filling • Repair and pulp regeneration
  • 185. Instrument modifications • Adini et al. examined the effects of cobalt coatings with impregnated fullerene-like WS2 nanoparticles on file fatigue and failure of NiTi files • In another study, the distal end of the file was modified by selective coating of endodontic files
  • 186. Enhancement of canal disinfection • Irrigants- nanoparticle-based antimicrobial photodynamic therapy • e.g. poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) and light against Enterococcus faecalis by transmission electron microscopy (TEM) • The synergism of light and MB-loaded nanoparticles led to approximately 2 and 1 log 10 reduction of colony-forming units (CFUs) in planktonic phase and root canals, respectively
  • 187. Medicaments • Nanoparticulates such as chitosan (CS-np) and zinc oxide (ZnO-np) have been shown to possess significant antibacterial properties ( a significant reduction in the thickness of Biofilm)
  • 188. Modifications on- Obturating materials • Bioactive glass 45S5 is one of the recent nanoparticles used in endodontic therapy. It has amorphous nanoparticles of 20-60 nm in size.
  • 189. • nanohydroxyapatite crystals in 279 nm showed superior antimicrobial activity (Actinomyces naeslundii, Peptostreptococcus anaerobius, Porphyromonas gingivalis, Porphyromonas endodontalis, and Fusobacterium nucleatum) as well as minimal microleakage. • nanocrystalline tetracalcium phosphate had significantly higher antimicrobial potency in an agar-diffusion test Modifications on- Sealers
  • 190. Retro-filling and root-repair materials • Mineral Trioxide Aggregate (MTA) has become the material of choice of retrograde filling
  • 191. Factors influencing the bioactivity of the NTs • Sterilization • Cell phenotype • Protein concentration • Protein distribution pattern
  • 193. Nanoceramics for Bone Regeneration in the Oral and Craniomaxillofacial Complex
  • 194.
  • 195. Nanoceramics and bone repair • porous hydroxyapatite (HA) and tricalcium phosphate (TCP) have been shown to have excellent osteoconductive properties, but their biodegradation is poor • HA: nanometer-sized needlelike crystals of approximately 5-20 nm width by 60 nm length • nanOsss bone void filler, Ostims
  • 196. Nanomaterials is superior to conventional mat: for bone regeneration Nanotechnology for craniofacial bone and cartilage tissue engineering
  • 197. Nanotechnology for craniofacial bone and cartilage tissue engineering • Due to the biomimetic features and excellent physicochemical properties, nanomaterials have been shown to improve adhesion, proliferation, and differentiation of cells, which would finally guide tissue regeneration • Synthetic and natural polymers are excellent candidates for bone/cartilage tissue engineering application due to their biodegradability and ease of fabrication
  • 198. Nano & Oral Medicine
  • 200.
  • 201.
  • 202.
  • 203.
  • 205. Saliva as a biofluid for disease detection
  • 206. Saliva as a biofluid for disease detection
  • 207. Saliva as a biofluid for disease detection
  • 208.
  • 209. Applications of Micro Electromechanical Systems (MEMS) Nano Electromechanical Systems (NEMS) in salivary diagnostics
  • 211. Nanogel for Local Anaethesia • Nanogels are probably one of the best candidates due to the lesser pain during injection and longer blood circulation time. • Tan et al. reported the nanogel systems for LAs such as bupivacaine poly(DL-lactide-co- glycolide) nanospheres, procaine hydrochloride (PrHy) hydrogel delivery systems and showed that the drug release can be delayed over 7-15 h
  • 212. Nanorobots -Curing the hypersensitivity • Microscopic studies reported earlier show that when dentin is exposed for 5 min to fluids like red and white wine, citrus fruit juices, apple juice, and yogurt, they remove the smear layer and open up dentinal tubules • the construction of reconstructive dental nanorobots, using native biological materials, could selectively and precisely occlude specific tubules within minutes, offering patients a quick and permanent cure
  • 213. Nanorobotic dentifrices • a caries vaccine may be available in near future • Dentifrice robots would also provide a continuous barrier to halitosis, since bacterial putrefaction is the central metabolic process involved in oral malodor • Artificial phagocytes called microbivores could patrol the bloodstream, seeking out and digesting unwanted pathogens including bacteria, viruses, or fungi
  • 214. Challenges of biomaterials • The successful use of biomaterials presents numerous challenges. A major one is the issue of maintenance, and in particular that most devices are implanted well into the body and therefore not freely available for inspection or repair • Life expectancy in the wealthier parts of the world is now of the order of 80 years, which means that many people now outlive (overstay) the useful life of their own connective tissue
  • 215. Toxicity of nanoparticles 1. Cytotoxicity of one or more of the nanoparticle constituents which is an inherent property of the chemical compound 2. Cytotoxicity of one or more of the degradation products of the nanoparticle constituents 3. Endocytosed nanoparticle-mediated apoptosis (cell death) 4. Nanoparticle-mediated cell membrane lysis
  • 216. Nanoparticle Cytotoxicity to Mammalian Cells
  • 217. References 1. Chemistry of Medical and Dental Material by John W. Nicholson (2002) 2. Dental biomaterials- Imaging, testing and modelling by Richard Curtis (2008) 3. Nanobiomaterials in Clinical Dentistry by Karthikeyan Subramani (2013) 4. Advanced Biomaterials and biodevices by Ashutosh Tiwari ( 2014)
  • 218. Thanks for your kind attention