TABLE OF CONTENTS

SR. no. Content

1. Introduction

2. Nanostructures

3. Approaches to nanotechnology

4. Nanomedicine

5. Nanotechnology in Dental Sciences

6. Preventive Aspect of Nanotechnology in Dentistry

7. Future Scope of Nanodentistry

8. Hazards of Nanotechnology

9. Conclusions

10. References

1
 INTRODUCTION

SIZE DOES MATTER – SMALL MAKES A LOT OF DIFFERENCE!

INTRODUCTION

The human characteristics of curiosity, wonder and genuinity are as old as mankind. For
many years, people around the world have been harnessing their curiosity into inquiry and the process of
scientific methodology. Science is the fuel for the engine of technology. Today the revolutionary development
of nanotechnology has become the most highly energized discipline in science and technology.1

Nanotechnology is the science and engineering involved in design, synthesis,

characterization and application of materials and devices whose smallest unit of measurement in at least one
dimension is on the nanometer scale.2
The word ―nano‖ is derived from a Greek word ―nannos‖ which means ―dwarf.‖ Nanometer
means one millionth of a meter (10-9 meter).3 Literature has given two concepts of nanotechnology i.e. broad
and narrow concept. Broad concept signifies a technology smaller than micro technology while, the narrow
concept, program and manipulate matter with molecular precision.4
The growing interest in the future medical applications of nanotechnology is leading to the
emergence of a new field called Nanomedicine. Many novel nanotechnology products are on the way and new
treatment modalities are also proposed. The science and technology of diagnosing, treating, and preventing
disease and traumatic injury, relieving pain, and preserving and improving human health, using nanoscale -
structured materials.5
Nanotechnology is manipulating matter at the nanometer level and application of the same to
medicine is called nanomedicine. Nanotechnology holds promise for advanced diagnostics, target drug
delivery and biosensors. In the long term, medical nanorobots will allow instant pathogen diagnosis and
extermination, individual cell survival in vivo and improvement of natural function.6
Nanotechnology helps us to exploit the atomic or molecular properties of materials.
Growing interest in the future medical applications of nanotechnology is leading to the emergence of a new
field called ―NANOMEDICINE‖ – the science and technology of diagnosing treating, preventing disease and

2
of preserving, improving human health using nanoscale – structured materials, biotechnology and nanorobots
. Similarly, development of ―NANODENTISTRY‖ will make possible the maintenance of comprehensive oral
health by employing nonmaterial, biotechnology and dental nanorobots. Dental nanorobotics is the most
challenging and exciting approach to nanodentistry. It will allow precisely controlled oral analgesia, dentition
replacement therapy and nanometer-scale restorative dentistry. New treatment opportunities include dentition
renaturalization, permanent hypersensitivity cure, complete orthodontic realignments during a single office
visit and continuous oral health maintenance using mechanical dentifrobots.

In literature it is common to distinguish four characteristics scales to describe the hierarchical

constitution of materials
• The nanoscopic scale with a characteristic length of 10 -9m or a few nanometers.
• The microscopic scale with a characteristic length of 10 -6 m or a few micrometers

The mesoscopic scale with a characteristic length of 10 -4m or hundreds of micrometers.

The macroscopic scale with a characteristic length of 10 -2m or centimeters and more.7

Nanoparticles are the simplest form of structures with sizes in the nm range. In principle any
collection of atoms bonded together with a structural radius of < 100 nm can be considered a nanoparticle.
These particles can include, e.g., fullerens, metal clusters (agglomerates of metal atoms), large molecules, such
as proteins, and even hydrogen-bonded assemblies of water molecules, which exist in water at ambient
temperatures. Nanoclusters have at least one dimension between 1 and 10 nanometers and a narrow size
distribution. Nanopowders are agglomerates of ultrafine particles, nanoparticles, or nanoclusters. Nanometer-
sized single crystals, or single-domain ultrafine particles, are often referred to as nanocrystals. Nanoparticles
are very common in nature - for instance proteins exist in almost all biological systems, metal-oxide
nanoparticles are easily produced etc .8

3
PROPERTIES:
Physical properties of nanoparticles:
Nanoparticles are unique because of their large surface area and this dominates the
contributions made by the small bulk of the material. Zinc oxide particles have been found to have superior
UV blocking properties compared to its bulk substitute. This is one of the reasons why it is often used in the
preparation of sunscreen lotions.9

Other examples of the physical properties of nanoparticles:

 Color – Nanoparticles of yellow gold and gray silicon are red in color
 Gold nanoparticles melt at much lower temperatures (~300 °C for 2.5 nm size) than the gold slabs
(1064 °C)
 Absorption of solar radiation in photovoltaic cells is much higher in nanoparticles than it is in thin
films of continuous sheets of bulk material - since the particles are smaller, they absorb greater
amount of solar radiation.9

There are three major physical properties of nanoparticles, and all are interrelated:

(1) They are highly mobile in the free state (e.g., in the absence of some other additional influence, a
10-nm-diameter nanosphere of silica has a sedimentation rate under gravity of 0.01 mm/day in
water).

(2) They have enormous specific surface areas (e.g., a standard teaspoon, or about 6 ml, of 10-nm-
diameter silica nanospheres has more surface area than a dozen doubles-sized tennis courts; 20
percent of all the atoms in each nanosphere will be located at the surface).

(3) They may exhibit what are known as quantum effects. In addition, nanoparticles can be
classified as hard (e.g., titania [titanium dioxide], silica [silica dioxide] particles, and fullerenes) or
as soft (e.g., liposomes, vesicles, and nanodroplets). Thus, nanoparticles have a vast range of
compositions, depending on the use or the product.

The high surface area to volume ratio of nanoparticles provides a tremendous driving
force for diffusion, especially at elevated temperatures. Sintering can take place at lower temperatures, over
shorter time scales than for larger particles. In theory, this does not affect the density of the final product,
4
though flow difficulties and the tendency of nanoparticles to agglomerate complicates matters. Moreover,
nanoparticles have been found to impart some extra properties to various day to day products. For example, the
presence of titanium dioxide nanoparticles imparts what we call the self-cleaning effect, and, the size being
nano-range, the particles cannot be observed. Zinc oxide particles have been found to have superior UV
blocking properties compared to its bulk substitute. This is one of the reasons why it is often used in the
preparation of sunscreen lotions,10 is completely photostable.11

Formation of suspensions:

An important physical property of nanoparticles is their ability to form suspensions.

This is possible since the interaction of the particle surface with the solvent is strong enough to overcome
density differences. In bulk materials, this interactions usually result in a material either sinking or floating in a
liquid.9

Optical properties of nanoparticles:

Individual energy levels and energy level separations are also dependent on the size of
the clusters, which therefore affect the energies needed for the transitions of electrons to excited states.
Clusters of different sizes will therefore have different absorption spectra – and hence different colors.
Nanoparticles also often possess unexpected optical properties as they are small enough to confine their
electrons and produce quantum effects. One example of this is that gold nanoparticles appear deep red to black
in solution.9

Magnetization and other properties of nanoparticles:

Interesting magnetic properties have also been observed in small clusters. In a cluster,
the magnetic moment of each atom will interact with the moments of the other atoms, and can force all the
moments to align in one direction with respect to some symmetry axis of the cluster – the cluster will have a
net magnetic moment, it will be magnetized. As cluster size decreases it therefore becomes easier for them to
exhibit ferromagnetic behaviour. In some cases, even clusters made up of nonmagnetic atoms can have a net
magnetic moment. For instance rhenium clusters show a pronounced increase in their magnetic moment when
they contain less than 20 atoms. For clusters with less than 15 atoms these moments are fairly large. Other
properties unique among nanoparticles are quantum confinement in semiconductor particles, surface plasmon
resonance in some metal particles and superparamagnetism in magnetic materials.9

5
 For example, ferroelectric materials smaller than 10 nm can switch their
magnetization direction using room temperature thermal energy, thus making them unsuitable for memory
storage. Thus this property is not always desired in nanoparticles.9

Diffusion properties of nanoparticles:

At elevated temperatures especially, nanoparticles possess the property of diffusion.
Sintering can take place at lower temperatures, over shorter time scales than for larger particles. Although this
does not affect the density of the final product but there is a chance of agglomeration.9

Hard nanoparticles
Clay nanoparticles, when incorporated into polymer matrices, increase reinforcement,
leading to stronger plastics verifiable by a higher glass transition temperature and other mechanical property
tests. These nanoparticles are hard, and impart their properties to the polymer (plastic). Nanoparticles have
also been attached to textile fibers in order to create smart and functional clothing.9 Also in food
packaging,flame retardants( products with nanoclays and hydroxide nanoparticles were associated with fewer
emissions of harmful fumes than products containing certain other types of additives),batteries &
supercapacitors, nanoceramics, LED‘s.9

Semisolid or soft nanoparticles

Semi-solid and soft nanoparticles have been manufactured. Of these notable is the
liposome. Various types of liposome nanoparticles are currently used clinically as delivery systems for
anticancer drugs, antibiotics and antifungal drugs and vaccines.9

The development of nanoparticles to aid in the delivery of a drug to the brain via
inhalation holds considerable promise for the treatment of neurological disorders such as Parkinson
disease, Alzheimer disease, and multiple sclerosis.

Dimensionality
Nanoparticles are generally classified based on their dimensionality, morphology,
composition, uniformity, and agglomeration.

6
  1D nanomaterials

These are one dimensional in the nanometer scale are typically thin films or surface
coatings. Example:-The circuitry of computer chips and the antireflection and hard coatings on
eyeglasses, semiconductor miniaturization.

 2D nanomaterials

Two-dimensional nanomaterials have two dimensions in the nanometer scale. These

include 2D nanostructured films, with nanostructures firmly attached to a substrate, or nanopore
filters used for small particle separation and filtration. Example:- Asbestos fibers are an example of
2D nanoparticles.

 3D nanomaterials

Materials that are nanoscaled in all three dimensions are considered 3D nanomaterials.
Example: - These include thin films deposited under conditions that generate atomic-scale porosity,
colloids, and free nanoparticles with various morphology.9

IMPORTANCE OF NANOPARTICLES:-

Nanoparticles play an important role in a number of these applications. ―NPs,‖ which in

general terms are defined as engineered structures with diameters of < 100 nm, are devices and systems
produced by chemical and/or physical processes having specific properties14.
The reason why nanoparticles (NP) are attractive for such purposes is based on their
important and unique features, such as their surface to mass ratio, which is much larger than that of other
particles and materials, allowing for catalytic promotion of reactions, as well as their ability to adsorb and
carry other compounds. The reactivity of the surface originates from quantum phenomena
(Quantum, discrete natural unit, or packet, of energy, charge, angular momentum, or other physical property.)
Light, for example, appearing in some respects as a continuous electromagnetic wave, on the submicroscopic
level is emitted and absorbed in discrete amounts, or quanta; and for light of a given wavelength, the
magnitude of all the quanta emitted or absorbed is the same in both energy and momentum. These particle-like
packets of light are called photons, a term also applicable to quanta of other forms of electromagnetic energy

7
such as x rays and gamma rays. Submicroscopic mechanical vibrations in the layers of atoms comprising
crystals also give up or take on energy and momentum in quanta called photons.
All phenomena in submicroscopic systems (the realm of quantum mechanics) exhibit
quantization: observable quantities are restricted to a natural set of discrete values. When the values are
multiples of a constant least amount, that amount is referred to as a quantum of the observable and can make
nanoparticles unpredictable since, immediately after generation, nanoparticles may have their surface
modified, depending on the presence of reactants and adsorbing compounds, which may instantaneously
change with changing compounds and thermodynamic conditions.

Therefore, on one hand, nanoparticles have a large (functional) surface which is able to bind,
adsorb and carry other compounds such as drugs, probes and proteins. On the other hand, nanoparticle has a
surface that might be chemically more reactive compared to their fine analogues 15.

NANOMEDICINE
 Drug delivery
 Diagnostic aids
 As biomarkers
 Stem cell imaging in MRI
 Microbivore (nanorobotic phagocytes)
 Genes
 Cytobots and karyobots
 Respirocytes
 Nanorobotic surgeon (A surgical nanorobot)
 Nanosensors16

NANODENTISTRY
 Local anesthesia
 Hypersensitivity cure
 Nanorobotic dentifrice [dentifrobots]

8
  Dental durability and cosmetics
 Orthodontic treatment
 Photosensitizers and carriers
 Major tooth repair
 Bionic mandible
 Skin grafts
 Detection and treatment of oral cancer16

The main purpose is, therefore, to provide an early glimpse of nanodental applications and
to illustrate their potentially far-reaching impact on clinical dental practice. It shall also present some potential
applications such as in local anesthesia, reconstruction of dental hard tissues, orthodontic treatment and disease
prevention. The expected development of nanodentistry, which might see its earliest practical uses within the
next 10 to 20 years, in the context of today‘s trends in dental science and practice.

9
 NANOSTRUCTURE

 Nanopores
 Nanotubes
 Quantum dot.
 Nanoshells
 Dendrimers
 Nanocapsules and Nanospheres (Polymeric nanoparticles)
 Liposomes
 Polymeric micelles
 Solid Lipid Nanoparticles (SLN’s)

 NANOPORES

These can be about 20nm in a diameter (Figure.1). They are integrated into artificially
constructed encapsulated cells of silicon wafers. These pores allow small molecules like oxygen, glucose and
insulin to pass, however they prevent large immune system molecules like immunoglobins to leave the cell.
This way rat pancreatic cell are microencapsulated, they receive nutrients and release insulin through
nanopores being totally isolated from their neighboring environment i.e. foreign cells. 17

Figure. 1: NANOPORES

10
 QUANTUMDOT/NANODOTS
Silicon nanocrystals with exceptional optical properties that can be used to design probes
that monitor biological experiments with greater sensitivity. Previously organic dyes were used but they tended
to fade. It allows for different types of molecules to be detected at the same time using different dyes using
simple light. As compared to the present method which requires each dyes to be illuminated with a specific
wavelength in order to shine brightly enough so that it can be detected. (Figure 2) 17

Figure 2: NANODOTS

 DENDRIMERS
Are nanostructured materials, which are tree-shaped synthetic materials which have a
branching system starting out from a core (as shown in fig 3). It has potential therapeutic applications as the
group of atoms that form its outer boundary can consist of heavier molecular groups that can act as hooks and
therefore attach on to molecules such as DNA. They can act as effective therapeutic agents because they can
insert DNA into cells without triggering an immune system response. They enter into the cell by a process
called endocytosis. In this process the cell membrane fuses with the dendrimer to form a kind of vesicle
(bubble). This allows the dendrimer to enter the cell, once inside the DNA now becomes a part of the cell‘s
genome.17

11
 Figure 3: DENDRIMERS

 NANORODS & NANOTUBES

These are rod-shaped particles with diameters typically ranging from 15-50 nm (Figure 4 &
5). Gold nanorods have their dimensions by nanometer however each individual‘s size depends on how many
times it has gone through its replication cycle i.e. its ―generations.‖ It has potential therapeutic applications as
the group of atoms.17

Figure 4: NANORODS Figure 5: NANOTUBES

 LIPOSOMES
Liposomes were the first carriers introduced for topical delivery of drugs and, since then, they
have been extensively studied.22 They present advantages for example not being toxic or invasive, as well as they are
able to deliver hydrophilic and/or lipophilic substances. Many drugs and cosmetic ingredients are already on the
marked in liposomal formulations, presenting better dose/effect ratio and less adverse reactions compared to the free
substances at the same concentration.23 In this way, some reviews have been consecrated to describe and discuss the
preparation, physico-chemical characterization and cutaneous applications of liposomes.23,24

12
 Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely
enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids.(Figure 6)
Liposomes are characterized in terms of size, surface charge and number of bilayers. It exhibits number of
advantages in terms of amphiphilic character, biocompatibility, and ease of surface modification rendering it a
suitable candidate delivery system for biotech drugs. Liposomes have been used successfully in the field of
biology, biochemistry and medicine since its origin. These alter the pharmacokinetic profile of loaded drug to
a great extent especially in case of proteins and peptides and can be easily modified by surface attachment of
polyethylene glycol-units (PEG) making it as stealth liposomes and thus increase its circulation half-life.21

a b

c d e

Figure 6: TYPES OF NANOPARTICLES

NANOCRYSTALS AND NANOSUSPENSION

Nanocrystals are aggregates of around hundreds or thousands of molecules that combine
in a crystalline form, composed of pure drug with only a thin coating comprised of surfactant or combination
of surfactants. Problems typical of poorly soluble drugs like reduced bioavailability, improper absorption
pattern and problems of preparing the parenteral dosage form may be resolved by formulation as
nanocrystals.18

13
 This has several benefits, unlike carrier-based nanoparticles in which extent of
loading may be low. Only a minimum quantity of surfactants needs to be added in nanocrystals for steric and
electrostatic surface stabilization. Moreover, administration of high drug levels with depot release can be
achieved if dissolution is sufficiently slow. As pure drug is used and no carrier is needed, eliminating potential
toxicity issues associated with the carrier molecule.18
Nanocrystal technology can be utilized for many dosage forms. Nanoparticles offer
the potential for targeting the mucosa of the gastrointestinal tract after oral administration, and targeting the
cells of the mononuclear phagocytic system (MPS) to treat infections of the MPS such as fungal mycobacterial
infections and leishmaniasis, thus serving as a favourable delivery system for drugs like amphotericin B,
tacrolimus, etc. The size of nanocrystals allows for safe and effective passage through capillaries. Potential of
nanocrystals can be inferred by the FDA approval of Rapamune®, containing sirolimus which is an
immunosuppressant drug to prevent graft rejection in children after liver transplantation and Emend®, which
contains a prepitant, MK 869, is used in the treatment of emesis associated with the cancer chemotherapy.18

SOLID LIPID NANOPARTICLES

Solid lipid nanoparticles (SLN) were developed at the beginning of the 1990s as an
alternative carrier system to emulsions, liposomes and polymeric nanoparticles as a colloidal carrier system for
controlled drug delivery. Main reason for their development is the combination of advantages from different
carriers systems like liposomes and polymeric nanoparticles. SLN have been developed and investigated for
parenteral , pulmonal and dermal application routes. Solid Lipid Nanoparticles consist of a solid lipid matrix, where
the drug is normally incorporated, with an average diameter below 1 μm.66 To avoid aggregation and to stabilize
the dispersion, different surfactants are used that have an accepted GRAS (Generally Recognized as Safe) status.
Nanoparticles are also produced by high pressure homogenisation as described for nanosuspensions.

SLN have been considered as new transfection agents using cationic lipids for the matrix
lipid composition. Cationic solid lipid nanoparticles (SLN) for gene transfer can be formulated using the same
cationic lipids as for liposomal transfection agents. In comparison to DOTAP liposomes tested cationic
nanoparticles liposomes showed the same transfection rate and gene expression as liposomes. Cationic lipid
composition seems to be more dominant for in vitro transfection performance than the kind of colloidal structure it
is arranged in. Hence, cationic SLN extend the range of highly potent non-viral transfection agents by one with
favourable and distinct technological properties.18

14
POLYMERIC NANOPARTICLES
The use of polymeric materials for encapsulating drugs or other active substances is an
important approach to mask the physico-chemical intrinsic properties of substances facilitating their skin
penetration.25 Polymeric nanoparticles are carrier systems presenting diameters lower than 1 µm that can be
named nanocapsules or nanospheres depending on their composition. The presence of oil in the nanocapsules
leads to a vesicular structure while its absence in nanospheres provide a matricial organization of the
polymeric chains.19 Considering the encapsulation mechanisms26, the drug can be entrapped, dispersed,
dissolved within or adsorbed on the nanoparticles (Figure 7 & 8).19

Figure 7: Encapsulation mechanism models: drug entrapped in, dissolved or dispersed

within, and adsorbed on: a). nanocapsules and b). nanospheres.

Figure 8: Structure of nanocapsule and nanosphere.

15
POLYMERIC MICELLES
A plethora of formulation techniques have been reported in the literature for
targeting drugs to specific sites. Polymeric micelles (PMs) can be targeted to tumor sites by passive as well as
active mechanisms. Some inherent properties of PMs, including size in the nanorange, stability in plasma,
longevity in vivo, and pathological characteristics of tumor allow PMs to be targeted to the tumor site by a
passive mechanism called the enhanced permeability and retention effect. PMs formed from an amphiphilic
block copolymer are suitable for encapsulation of poorly water-soluble, hydrophobic anticancer drugs.
Other characteristics of PMs such as separate functionality at the outer shell are
useful for targeting the anticancer drug to tumor by active mechanisms. PMs can be conjugated with many
ligands such as antibody fragments, epidermal growth factors, α2-glycoprotein, transferrin, and folate to target
micelles to cancer cells (Figure 9). Application of heat or ultrasound is the alternative methods to enhance drug
accumulation in tumoral cells. Targeting using micelles can also be directed toward tumor angiogenesis, which
is a potentially promising target for anticancer drugs.20

Figure 9: Structure of Polymeric micelle

16
 APPROACHES TO NANOTECHNOLOGY

Three approaches for the synthesis of nanoparticles are Top-down approach, Bottom-up
approach and Functional approach. In top-down approach, particles are synthesized in the conventional manner and
made smaller by grinding or milling. While in bottom-up approach, nanoparticles are synthesized by direct
molecular synthesis and bonding. i.e. they are synthesized from molecular level. The functional approach, on the
other hand, does not give importance to the method of production of a nanoparticle, rather, it emphasizes on
production of nanoparticle with a specific use.13,26
Current research is not exclusively focused on achieving assemblers. Instead, research
is directed towards the production of a wide array of different nanoscale structures. The fabrication techniques
of these structures can be divided into 2 approaches: ―top- down‖ and ―bottom up‖.
The 'top-down' techniques that are used to manufacture nanoscale structures are
mostly extensions of methods already employed in small-scale assembly at the micron scale. By further
miniaturization, the nanodimension is entered. 'Bottom-up' fabrication methods for manufacture are the
methods used for producing nanoscale structures.
The various nanostructures are
1. Nanopores
2. Nanotubes
3. Quantum dots
4. Nanoshells
5. Dendrimers

Nanodentistry as bottom-up approach:-

1. Local anesthesia
In the era of nanodentistry, a colloidal suspension containing millions of active analgesic
micron-size dental robots will be instilled on the patient's gingiva. After contacting the surface of crown or
mucosa, the ambulating nanorobots reach the pulp via the gingival sulcus, lamina propria, and dentinal tubules.
Once installed in the pulp, the analgesic dental robots may be commanded by the dentist to shut down all
sensitivity in any particular tooth that requires treatment. After oral procedures are completed, the dentist
orders the nanorobots to restore all sensation, to relinquish control of nerve traffic, and to egress from the tooth
by similar pathways used for ingress.

17
2. Hypersensitivity cure
Dentin hypersensitivity may be caused by changes in pressure transmitted
hydrodynamically to the pulp. This is based on the fact that hypersensitive teeth have 8 times higher surface
density of dentinal tubules and tubules with diameters twice as large than nonsensitive teeth. Dental
nanorobots could selectively and precisely occlude selected tubules in minutes, using native biological
materials, offering patients a quick and permanent cure.6

3. Nanorobotic dentifrice [dentifrobots]

Subocclusal dwelling nanorobotic dentrifice delivered by toothpaste could patrol all
supragingival and subgingival surfaces at least once a day, metabolizing trapped organic matter into harmless
and odorless vapors and performing continuous calculus debridement.6
These invisibly small dentifrobots [1-10 micron], crawling at 1-10 microns/sec, would
be inexpensive, purely mechanical devices, that would safely deactivate themselves if swallowed and would be
programmed with strict occlusal avoidance protocol.6

4. Dental durability and cosmetics

Tooth durability and appearance may be improved by replacing upper enamel layers with
pure sapphire and diamond which can be made more fracture resistant as the nanostructured composites,
possibly including embedded carbon nanotubes. 6

5. Orthodontic treatment
Orthodontic nanorobots could directly manipulate the periodontal tissues, allowing rapid
and painless tooth straightening, rotating, and vertical repositioning within minutes to hours. 6

6. Photosensitizers and carriers

Quantum dots can be used as photosensitizers and carriers. They can bind to the antibody
present on the surface of the target cell and when stimulated by UV light, they can give rise to reactive oxygen
species and thus will be lethal to the target cell.6

7. Diagnosis of oral cancer

NANOELECTROMECHANICAL SYSTEMS (NEMS) convert (bio) chemical to electrical signal.
CANTILEVER ARRAY SENSORS:-

18
 Ultrasensitive mass detection technology:
 Picogram (10-12) -bacterium
 Femtogram (10-15) -virus
 Attogram (10-18) -DNA
MULTIPLEXING MODALITY
Sensing large numbers of different biomolecules simultaneously in real time.
APPLICATIONS:-
1. Diagnosis of diabetes mellitus and cancer.
2. Detection of bacteria, fungi, and viruses.6

8. Treatment of oral cancer:-

NANOMATERIALS FOR BRACHYTHERAPY
BrachySil™ (Sivida, Australia) delivers 32P, clinical trial
DRUG DELIVERY ACROSS THE BLOOD-BRAIN BARRIER
More effective treatment of brain tumors, Alzheimer's, Parkinson's in development
NANOVECTORS FOR GENE THERAPY
Non-viral gene delivery systems.6

Nanodentistry as top-down approach

1. Nanocomposites :-
Nanoproducts Corporation has successfully manufactured nonagglomerated discrete
nanoparticles that are homogeneously distributed in resins or coatings to produce nanocomposites. The
nanofiller used includes a strict occlusal avoidance protocol. aluminosilicate powder having a mean particle
size of 80 nm and a 1:4 M ratio of alumina to silica and a refractive index of 1.508.6

Advantages:
 Superior hardness
 Superior flexural strength, modulus of elasticity, and translucency
 50% reduction in polymerisation shrinkage
 Excellent handling properties
Trade name: Filtek O Supreme Universal Restorative Pure Nano O.
19
 2. Nanosolution
Nanosolutions produce unique and dispersible nanoparticles, which can be used in bonding
agents. This ensures homogeneity and ensures that the adhesive is perfectly mixed everytime.6
Trade name: Adper O Single Bond Plus Adhesive Single Bond

3. Impression materials
Nanofillers are integrated in vinylpolysiloxanes, producing a unique addition of siloxane
impression materials.The material has better flow,improved hydrophilic properties, and enhanced detail
precision6.
Trade name: Nanotech Elite H-D.

4. Nanoencapsulation
SWRI [South West Research Institute] has developed targeted release systems that
encompass nanocapsules including novel vaccines, antibiotics, and for drug delivery.6
At present, targeted delivery of genes and drugs to human liver has been developed by Osaka

University in Japan [2003]. Engineered Hepatitis B virus envelope L particles were allowed to form hollow
nanoparticles displaying a peptide that is indispensable for liver-specific entry by the virus in humans. Future
specialized nanoparticles could be engineered to target oral tissues, including cells derived from the
periodontium.6

5. Otherproducts manufactured by SWRI

a. Protective clothing and filtration masks, using antipathogenic nanoemulsions and nanoparticles.

b. Medical appendages for instantaneous healing

 Biodegradable nanofibres -delivery platform for haemostatic.

 Wound dressings with silk nanofibres in development.

 Nanocrystalline silver particles with antimicrobial properties on wound dressings [ Acticoat™,

UK]6
c. Bone targeting nanocarriers.
Calcium phosphate-based biomaterial has been developed.

20
 This bone biomaterial is an easily flowable, moldable paste that conforms to and interdigitates
with host bone. It supports growth of cartilage and bone cells.6

6. Nanoneedles:-
Suture needles incorporating nano-sized stainless steel crystals have been developed.
Trade name: Sandvik Bioline, RK 91™ needles [AB Sandvik, Sweden].6
Nanotweezers are also under development which will make cell- surgery possible in near future.

7. Bone replacement materials:-

Hydroxyapatite nanoparticles used to treat bone defects are
 Ostim® (Osartis GmbH, Germany) HA
 VITOSS® (Orthovita, Inc., USA) HA + TCP
 NanOss™ (Angstrom Medica, USA) HA.6

21
 NANOMEDOCINE

Nanomedicine, a branch of nanotechnology, refers to highly specific medical intervention at

the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Research
in nanotechnology began with applications outside of medicine and is based on discoveries in physics and
chemistry. This is because it is essential to understand the physical and chemical properties of molecules or
complexes of molecules in order to control them. The same holds true for the molecules and structures inside
living tissues.

Nanomedicine is the medical application of nanotechnology that will hopefully lead to useful
research tools, advanced drug delivery systems, and new ways to treat disease or repair damaged tissues and
cells. Drug delivery is currently the most advanced application of nanotechnology in medicine. Nanoscale
particles are being developed to improve drug bioavailability, a major limitation in the design of new drugs.
Poor bioavailability is especially problematic with newer and still experimental RNA interference therapy.

Lipid or polymer-based nanoparticles are taken up by cells due to their small size, rather than
being cleared from the body. These nanoparticles can be used to shuttle drugs into cells which may not have
been accepted the drug on their own. The nanoparticle may also be able to specifically target certain cell types,
possibly reducing toxicity and improving efficacy. 27

Such technology has enormous medical implications. Programmable nanorobotic devices

would allow physicians to perform precise interventions at the cellular and molecular level. Medical
nanorobots have been proposed for gerontological applications, in pharmaceutical research and clinical
diagnosis, and in dentistry. Other applications include mechanically reversing atherosclerosis, improving
respiratory capacity, enabling near instantaneous hemostasis, supplementing the immune system, rewriting or
replacing DNA sequences in cells, repairing brain damage and resolving gross cellular insults, whether caused
by ―irreversible‖ processes or by cryogenic storage of biological tissues.28

Growing interest in the future medical applications of nanotechnology is leading to the

emergence of a new field called ―nanomedicine‖, the science and technology of diagnosing, treating and
preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health,
using nanoscale-structured materials, biotechnology and genetic engineering, and eventually complex
molecular machine systems and nanorobots.29

22
 Nanotechnology holds promise for advanced diagnostics, target drug delivery and biosensors.
In the long term, medical nanorobots will allow instant pathogen diagnosis and extermination, individual cell
survival in vivo and improvement of natural function.5

Nanomedicine as a Potential Platform for Therapeutic Application

Applications of nanotechnologies in medicine are especially promising, and areas such as

disease diagnosis, drug delivery targeted at specific sites in the body and molecular imaging are being
intensively investigated and some products are undergoing clinical trials. Nanotechnology is relatively new.
Although the full scope of contributions these technological advances will make in medicine is unexplored,
recent advances suggested nanotechnology will have a profound impact on disease prevention, diagnosis, and
treatment.28

The current generation of drugs is largely based on small molecules with a mass of 1000 Da
or less that circulate systemically28. Common deleterious consequences of systemic bio distribution include
toxicity to non-target tissues, difficulty in maintaining drug concentrations within therapeutic windows, and
metabolism and excretion of drugs, all of which can reduce efficacy. Drug solubility and cell permeability
issues are also common with small molecules and biologics.

Nanotechnology-based delivery systems could mitigate these problems by combining tissue-

or organ-specific targeting with therapeutic action. Multifunctional nano-delivery systems could also combine
targeting, diagnostic, and therapeutic actions.28

More than 90 years ago, Nobel laureate German immunologist Paul Ehrlich proposed the so-
called magic bullets artificial biochemical agents that would transport and release drugs at only desired sites in
the body. Targeting the delivery of drugs to diseased lesions is one of the important aspects of the drug
delivery systems.

To convey a sufficient dose of drug to the lesion, suitable carriers of drugs are needed.
Although opportunities to develop nanotechnology-based efficient drug delivery systems extend into all
therapeutic classes of pharmaceuticals, the development of effective treatment modalities for the respiratory,
central nervous system, and cardiovascular disorders remains a financially and therapeutically significant need.

23
 Many therapeutic agents have not been successful because of their limited ability to
reach to the target tissue. In addition, faster growth opportunities are expected in developing delivery systems
for anti-cancer agents, hormones, and vaccines owing to safety and efficacy shortcomings in their conventional
administration modalities. For example, in cancer chemotherapy, cytostatic drugs damage both malignant and
normal cells alike. Thus, a drug delivery strategy that selectively targets the malignant tumor is very much
needed.28

Additional problems include drug instability in the biological milieu and premature drug
loss through rapid clearance and metabolism. Similarly, high protein binding of certain drugs such as protease
inhibitors limits their diffusion to the brain and other organs. However, nanotechnology for drug delivery
applications may not be suitable for all drugs, especially those drugs that are less potent because the higher
dose of the drug would make the drug delivery system more massive, which would be difficult to administer.

Drug bioavailability is a related problem with potential nanotechnology solutions.

Nanotechnology is opening up new therapeutic opportunities for a large number of agents that cannot be used
28
effectively as conventional oral formulations, due to poor bioavailability. In some cases, reformulation of a
drug with smaller particle size may improve oral bioavailability. Nanoparticles formulations provide protection
for agents susceptible to degradation or denaturation in regions of harsh pH, and also prolong the duration of
exposure of a drug by increasing retention of the formulation through bioadhesion. Another broad application
of nanotechnology is the delivery of antigens for vaccination.

Mucosal immunity is extremely important in disease prevention, but continues to be

limited by both degradation of the vaccine and limited uptake. Recent advances in encapsulation and
development of suitable animal models have demonstrated that micro and nanoparticles are capable of
enhancing immunization. It has been shown that M cells in the Peyer‘s Patches of the distal small intestine are
capable of engulfing large microparticles and recent studies have explored the benefi ts of
nanoencapsulation.28

Nanomedicine as Diagnostic Purposes:-

Biomedical laboratory diagnosis plays a key role in today‘s health care. Most testing is
done on a macroscopic scale, for example, in micro titer plates. Size reduction of biomedical lab tests has
several advantages: Not only does it lead to a marked reduction of the sample volume needed for testing, but it

24
also results in a marked reduction of (potentially expensive) reagents such as monoclonal antibodies. Last but
not least, it may lead to a significant reduction in the time required. Moreover, the ability of current nanotools
to measure interaction microforces between individual molecules is most promising for biomedical testing
because this might eliminate the need for reagent labeling, a tedious and expensive step. Taken together, small
sized sample volumes and fast reaction times bring mobile testing devices into the reality.28,30

They indicate that there will be a strong trend toward point-of-care testing at the bedside or in
an ambulatory setting. One of the first applications of nanomedicine will be improved fluorescent markers for
diagnostic and screening purposes. Conventional fluorescent markers require complex color. Non-invasive
imaging techniques had a major impact in medicine over the past 25 years or so.

The current drive in developing techniques such as functional magnetic resonance imaging
(MRI) is to enhance spatial resolution and contrast agents. Nanotechnologies already offer the possibility of
intracellular imaging through attachment of quantum dots or synthetic chromophores to selected molecules,
for example, proteins, or by the incorporation of naturally occurring fluorescent proteins which, with optical
techniques such as confocal microscopy and correlation imaging, allows intracellular biochemical processes to
be investigated directly. 28,30

One application is improved imaging of the human (or any) body. Before you can treat a
disease, you must diagnose it. Advances in nanotechnology have led to the design and construction of
structures at the nanometer scale, in a precisely controlled manner. Amongst these improved nanostructures,
nanoprobes (particles <100 nm) have stimulated a strong interest in the area of biological and clinical
research. Unlike macroscale structures, nanoscale structures have optical and electronic properties that can be
tuned by the structure‘s size, shape or material composition.

These properties offer engineers, clinicians, and researchers an unlimited supply of

precursor materials for the design of contrast agents for imaging applications, optical switches for triggering
drug release, or for therapy Nanotechnology could significantly improve diagnostic capabilities.28,30

Nanomedicine will increase the efficiency and accuracy of diagnosis from samples of
body fluids. For example, some companies are attempting to develop microchips that use electrodes to
identify the dielectric properties of cancerous cells, viruses, and bacteria in body fluids. Nanomedicine could

25
result in non invasive devices that can enter the body to determine glucose levels, distinguish between normal
and cancerous tissues, and provide genetic screening for multiple diseases.

For example, researchers are working with a nanoscale needle that can probe cells for
carcinogenic chemicals.

Ultimately, research in this area could yield a tiny pill that will travel through the body
and provide a comprehensive diagnosis of the patient‘s health. There are even some who suggest that tiny
devices could be implanted to constantly monitor health. As one reporter speculated, a person in the future
may look at her watch, and it will read: ―Slow down, your pulse is too high, and you are about to have a heart
attack.‖28,30

NANOROBOTS:

An artificially fabricated object which are able to freely diffuse in the human body &
interact with specific cell at the molecular level by itself.31

Robert A. Freitas has described how medical nanorobots might utilise specific motility
mechanisms to crawl or swim through human body tissues with navigational precision, acquire energy, sense
and manipulate their surroundings, achieve safe cytopenetration (e.g., pass through plasma membranes such as
the odontoblastic process without disrupting the cell), and employ any of a multitude of techniques to monitor,
interrupt, or alter nerve impulse traffic in individual nerve cells in real time.5

To cure skin diseases, a cream containing nanorobots may be used. It could remove the right
amount of dead skin, remove excess oils & add missing oils; apply the right amounts of natural moisturizing
compounds.

Augment the immune system by finding and disabling unwanted bacteria and viruses.
(Figure 10).In the bloodstream it could remove/dissolve away at arteriosclerotic deposits, widening the
affected blood vessels, restore artery walls and artery linings to health, by ensuring that the right cells and
supporting structures are in the right places. This would prevent most heart attacks.28

26
Figure 10: A list of some of the applications of nanomaterials to biology or medicine:

NANOROBOT IN BLOOD NANOROBOT IN LUNG

N
A
N
O
R
O
B
O
ATTACKING VIRUS
T MOBILE CELL REPAIR
S
&
N
A
N
O
M
E
D
MOBILE CELL REPAIR I BIONANOELECTRONICS
C
I
N
E

FIGURE 10

LOCAL DRUG DELIVERY LOCAL DRUG DELIVERY

27
 1. Drug and gene delivery

2. Bio detection of pathogens

3. Detection of proteins

Nowadays diabetes, especially type 2 diabetes (which is strongly related to the Western diet
and life-style), has developed worldwide into an epidemic disease. Nanomedicine aims to provide novel
tools for diagnosis, therapy and point-of-care management of patients.
Several nanotechnological approaches were developed to improve life quality for patients with
insulin-dependent diabetes. They facilitate blood glucose management by non-invasive glucose
measurement as well as insulin administration mainly by delivering the fragile protein as protected and
targeted formulation via nasal or oral route.32
The oral or nasal insulin delivery by polymeric nanoparticles is discussed with focus on
physiological change either related to the disease, diabetes or age-related metabolic variations influencing
insulin release and bioavailability. One critical point is that new generations of targeted nanoparticle based
drugs are developed and optimized for certain metabolic conditions. These conditions may change with age
or disease. The influence of age-related factors such as immaturity in very young age, metabolic and
physiologic changes in old age or insufficient animal models are still under-investigated not only in
nanomedicine but also generally in pharmacology.32
Summarizing it can be noted that the bioavailability of insulin administered via routes others
than subcutaneously is comparably low (max. 60%). Moreover factors like changed gut permeability as
described for diabetes type 1 or other metabolic peculiarities such as insulin resistance in case of type 2
diabetes also play a role in affecting the development of novel nanoparticulated drug preparations and can be
responsible for unsuccessful translation of promising animal results into human therapy.32
In future insulin nanoparticle development for diabetes must consider not only requirements
imposed by the drug but also metabolic changes inflicted by disease or by age. Moreover new approaches
are required for prevention of the disease.

28
 Carbon nanotubes and gold nanoparticles are being used in a sensor that detects proteins
indicative of oral cancer. Tests have shown this sensor to be accurate in detecting oral cancer and provides
results in less than a hour.32
Researchers have developed a method to capture individual cancer cells circulating in the
blood stream. They use nanofibers coated with antibodies that bind to cancer cells, trapping the cancer cell
for analysis.32
A method for early detection of a disease uses nanoparticles that form clumps when they
attach to proteins or other molecules that indicate the disease being tested for. The test is intended to be
inexpensive and simple to perform. The solution turns blue if the nanoparticles are clumped around a protein
indicating the disease, if the protein is not present the solution is red.32
Alzheimer disease (AD) is the most common form of dementia in the elderly, with no current
therapy or definite diagnosis. Brain accumulation of amyloid-β (Aβ) peptides,eventually deposited as
plaques, is one of the pathological hallmarks of AD. Aβ accumulation has been hypothesized to result from
an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early
and late forms of AD and may contribute to the onset and progression of the disease.
Moreover, additional evidence suggests that about 80-90% of AD patients show cerebral
amyloid angiopathy (CAA), characterized by Aβ accumulation in brain blood vessel walls, altering the
functionality of the BBB. Among the different aggregation forms of Aβ, a body of evidence indicates that
soluble Aβ oligomers (Aβo), rather than insoluble deposits, such as Aβ fibrils (Aβf) and plaques,33,34,35,36,37
are primarily responsible for both neurodegeneration and synaptic impairment in AD. Therefore, in the last
years, many efforts have focused at preventing Aβo formation or disassembling existing aggregates.
Recently, a therapeutic strategy based on loweringthe levels of soluble Aβ assemblies in the brain and in the
cerebral blood vessel exploiting the peripheral-sink effect has been proposed. To this purpose, it has been
postulated that brain and plasma Aβ pools are in equilibrium through the BBB, andthat the peripheral
sequestration of Aβ may shift this equilibrium toward the peripheral blood circulation, eventually drawing
out the excess from the brain and/or from the brain vessels.38,39,40
MicroRNAs (miRNAs) directly regulate gene expression at a post-transcriptional
level and represent an attractive therapeutic target for a wide range of diseases. Here, we report a novel
strategy for delivering miRNAs to endothelial cells (ECs) to regulate angiogenesis, using polymer
functionalized carbon nanotubes (CNTs). CNTs were coated with two different polymers, polyethyleneimine
(PEI) or polyamidoamine dendrimer (PAMAM), followed by conjugation of miR-503 oligonucleotides as

29
 recognized regulators of angiogenesis.41 We demonstrated a reduced toxicity for both polymer-coated CNTs,
compared with pristine CNTs or polymers alone.
Moreover, polymer-coated CNT stabilized miR-503 oligonucleotides and allowed their
efficient delivery to ECs. The functionality of PAMAM-CNT-miR-503 complexes was further demonstrated
in ECs through regulation of target genes, cell proliferation and angiogenic sprouting and in a mouse model
of angiogenesis. This comprehensive series of experiments demonstrates that the use of polyamine-
functionalized CNTs to deliver miRNAs is a novel and effective means to regulate angiogenesis.41

4. Probing of DNA structure

5. Tumor diagnosis and destruction

6. Cell repair and regeneration

7. Treatment of atherosclerosis

1. Drug and gene therapy

a) Smart Drugs

Nanobodies® like Antibodies but smaller

Nanobodies® are a novel class of antibody-derived therapeutic proteins. Because of

their small size, unique structure and unparalleled stability, Nanobodies® combine the advantages of

conventional antibody therapeutics with key features of small-molecule drugs.42

b) Drug Delivery

Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to

improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery

systems is their ability to alter the pharmacokinetics and biodistribution of the drug.43

Nanoparticles have unusual properties that can be used to improve drug delivery. Where

larger particles would have been cleared from the body, cells take up these nanoparticles because of

30
their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs

through cell walls and into cells.43 (Figure 11 & 12)

Fig. 11 ; NANOINJECTORS

FIG. 12:- NANODRUGS

Efficiency is important because many diseases depend upon processes within the cell
and can only be impeded by drugs that make their way into the cell. Triggered response is one way
31
 for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on
encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug
delivery system where both hydrophilic and hydrophobic environments exist, improving the
solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can
eliminate this problem. If a drug is cleared too quickly from the body, this could force a patient to
use high doses, but with drug delivery systems clearance can be reduced by altering the
pharmacokinetics of the drug.43

Modes of drug delivery may be:

I. Bioadhesion:
II. Magnetics:
I. Bioadhesion:
The bioadhesive molecule attaches to the cell membrane it secretes the drugs inside from
where it is transported within the cell.
Bioadhesion also offers its use in drug delivery which usually consists of lectin and other
molecules with adhesive properties because these bind specifically to the receptors of the cell
membrane.
Once the bioadhesive molecule attaches to the cell membrane it secretes the drugs
inside from where it is transported within the cell.
This way bioadhesion allows for the transport of nanoscale drug systems by endocytosis.43
II. Magnetics:-
Magnetically controlling the release of drugs by the help of nanoparticles is another
method whereby drug delivery is benefiting from nanotechnology. This usually consists of magnetic
fluids which bind with and concentrate the drugs at the site of their delivery. Magnetic fluid usually
consists of magnetic nanoparticles floating in both organic and inorganic fluid.
Magnetic nanoparticles consist of iron based compounds of nanometer size. However
before these can be used within the body they have to be coated with materials that biodegradable,
non toxic, and biologically stable.43 These nanoparticles must also be compatible to the internal
environment of the cell. Magnetic nanoparticles have the ability to be attracted to distant magnetic

32
 fields, so it concentrates drugs at the site of the solid cancer tumor. This feature may also help in
thermotherapy.43
2. NANOWIRES
Nanowires can help to monitor changes in blood pressure. A new class of components have
been created using the piezoelectric effect in semi-conducting zinc oxide nanowires. These nanowires can
detect forces as small as a few piconewtons (10-12 N). It is roughly the force required for ―unzipping‖ a
DNA strand. A piezoelectric effect can produce a current when they are bent.44 (Figure 13)

Figure: 13: NANOWIRES

3. DETECTION OF PATHOGENS

Artificial phagocytes called ‗‗microbivores‘ (Figure 14) are developed through nanotechnology. They

patrol in bloodstream seeking out and digesting unwanted pathogens.

Figure 14: MICROBIVOR

33
 4. CANCER THERAPY:

A schematic illustration showing how nanoparticles or other cancer drugs might be used to

treat cancer.Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light.

When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide

for more accurate tumor removal.

Sensor test chips containing thousands of nanowires, able to detect proteins and other

biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages

from a few drops of a patient‘s blood28.(Figure 15)

Figure 15: Schematic representation of nanoparticles used to treat cancer

In vivo therapy:
Medical nanodevices would first be injected into a human body, and would then go to work in
a specific organ or tissue mass. The doctor will monitor the progress, and make certain that the

34
 nanodevices have gotten to the correct target treatment region. The doctor wants to be able to scan a
section of the body, and actually see the nanodevices congregated neatly around their target (a tumor
mass, etc.) so that he or she can be sure that the procedure was successful. Tracking movement can help
to determine how well drugs are being distributed or how substances are metabolized.
It is difficult to track a small group of cells throughout the body so scientists used to dye the
cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While
different color dyes absorb different frequencies of light, there was a need for as many light sources as
cells. A way around this problem is with luminescent tags.These tags are quantum dots attached to proteins
that penetrate cell walls. The dots can be random in size, can be made of bio-inert material, and they
demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the
frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency
required to make another group incandesce.28
Nanosystem's in cancer diagnostics
Nano-biotechnology offers a novel set of tools for the detection of cancer and contributes to early
detection of cancer. (Figure 16)

Figure 16: Diagram representing the mode of action of targeted multifunctional

nanoparticle (NP). The NP encapsulating a chemotherapy drug is targeted to the
cancer cell surface by the cancer-specific ligand. The NP then binds to the cancer cell
surface by recognizing the receptor, resulting in internalization of the NP by
endocytosis. Inside the cancer cell, the NP undergoes endosomal escape, leading to the

35
 release of the treatment cytotoxic drug, which then activates consecutive steps,
resulting in cell death.

Types of Nanosystem's:-
These include as tabulated in [Table no. 1 below] Application Of Nanotechnology In
Oncology Nanotechnology may have an impact on the key challenges in cancer diagnosis and therapy.
Diagnosing, treating, and tracking the progress of therapy for each type of cancer has long been a dream
among oncologists, and one that has grown closer to parallel revolutions in genomics, proteomics and
cell bio1ogy. Nanotechnology's greatest advantage over conventional therapies may be the ability to
combine more than one function. Recently, there is a lot of research going on to design novel
'Nanodevices' capable of detecting cancer at its earliest stages, pinpointing its location within the human
body and delivering chemotherapeutic drugs against malignant cells. The major areas in which
nanomedicine is being developed in oncology involve 45:
Early detection of tumor :-
Developing "smart" collection platforms for simultaneous analysis of cancer-associated
markers and designing contrast agents that improve the resolution of tumor area comparing with the
nearby normal tissues), and © Cancer treatment (creating nanodevices that can release chemotherapeutic
agents) :

1. Detection of tumor :-
Early detection of tumor will greatly increase survival rates with the reasonable assumption that
an in situ tumor will be easier to eradicate than one that has metastasized. Nanodevices and especially
nanowires can detect cancer related molecules, contributing to the early diagnosis of tumor. Nanowires having
the unique properties of selectivity and specificity can be designed to sense molecular markers of malignant
cells. They are laid down across a microfluidic channel and they allow cells or particles to flow through it.
Nanowires can be coated with a probe such as an antibody or oligonucleotide.
Proteins that bind to the antibody will change the nanowire's electrical conductance and this can
be measured by a detector. As a result, proteins produced by cancer cells can be detected and earlier diagnosis
of tumor can be achieved. Nanoparticle contrast agents are being developed for tumor detection purposes.
Labeled and non-labeled nanoparticles are already being tested as imaging agents in diagnostic procedures such
as nuclear magnetic resonance imaging. There are two main groups of nanoparticles:

36
 1) superparamagnetic iron oxides whose size is greater than 50 nm.
2) ultrasmall superparamagnetic iron oxides which are smaller than 50nm.45

Moreover, Quantum dots can be used to measure levels of cancer markers such as breast cancer marker Her-2,
actin, microfibril proteins and nuclear antigens.

TABLE NO. 1:- Types of Nanorobots & properties with their Applications
No. Type of Nanosystem Physical Properties Applications Advantages
Liposomes  Multilamellar They are used  Active and Passive
1. These are the closed vesicle vesicles in cancer delivery mode
forms of hydrated These consist of therapy, carrier  Flexible
phospholipids. several lipid bi-layers for antigens,  Aqueous preparations
These are of 3 types based separated from one pulmonary
on size and number of another by aqueous delivery,
bilayers. spaces. These are leishmaniasis,
 Multilamellar vesicles heterogeneous in ophthalmic
 Small unilamellar size, ranging from few drug
vesicles hundreds to thousands delivery.
 Large unilamellar of nm in
vesicles diameter.
 Small
unilamellar
vesicles (SUV’S)
<100nm
 Large
unilamellar
vesicles
(LUV’S)>100nm
These consist of a
single bi-layer
surrounding the
entrapped aqueous
space. Drug is either
entrapped in the
aqueous space or
intercalated into lipid
bi-layer of
liposomes, depending
on physicochemical
characteristics of the
drug.
2. Polymeric Nano Particles These are colloidal Application of Biodegradable
comprise of carrier, 10nm-1μm in these particles
37
 1.Nanocapsules size in oncology  Natural
2.Nanosphere. consisting of synthetic has  Synthetic
or natural polymers. exponentially
In these increased with
polymers, drugs are advent of
physically dissolved, biodegradable
entrapped, polymers.
encapsulated or Both natural
covalently attached to (albumin,
the polymer Chitosan,
matrix Heparin etc)
and
Synthetic (
 Nanocapsules Poly-L-
are systems in Lactide, Poly-
which drug is [L-glutamate]
confined to a Poly [D, L
cavity Lactide-
surrounded by Coglycolide],
unique [PEG, etc],
polymeric biodegradable
membrane polymers
 Nanospheres are being
are systems in exercised as
which the drug drug delivery
is systems
dispersed
throughout the
polymer matrix

3. Cantilevers  Nanoscale As a cancer  Cantilever provide

Researchers can read this cantilevers cell secretes its rapid and sensitive
change in real time and Are microscopic molecular detection of cancer-
provide not only flexible beams products, the related molecules
information about the resembling a row of antibodies
presence and dividing boards – are coated on the
the absence but also the built using cantilever
concentration of different semiconductor fingers
molecular expressions lithographic selectively
techniques and are bind to these
coated with molecules secreted
capable of binding to proteins,
the biomarkers of changing the
cancer like PSMA physical
(Prostate-Specific properties of
Membrane Antibody). the cantilever
and signaling
38
 the presence of
cancer.
4. Quantum dots (QD)  Their properties These have a  QDs are used as
These are semi conducting originate from large impact inorganic
materials consisting of a their physical on imaging, in- fluorophores, owing
semiconductor core coated size which vitro and to the fact that they
by a shell to improve optical ranges from 10- invivo offer significant
properties. 100A° in radius. detection and advantages
analysis of over conventionally
 The best biomolecules, used fluorescent
characteristics immunoassay, markers.
of QDs and and DNA
magnetic iron hybridization
oxide and in non-
nanoparticles viral
can be vectors for
combined to gene therapy.
create a single It has main
nanoparticle function in
probe that can labeling
yield clinically
of cells and
useful images of
both tumors therapeutic
and the tools for
molecules cancer
involved in treatment.
cancer.
5. Dendrimers  These are hyper These can  Low cytotoxic
They can be made more branched, tree- deliver  High bio-permeability
biocompatible compounds like structures bioactive
with and substances like
low cytotoxicity and high have drugs,
bio-permeability according compartmentali vaccines,
to zed chemical materials and
the requirements polymer. genes to
desired sites
6. Carbon Nanotubes  These are They scan  Economic
This technique can serve as hexagonal down DNA  Identifies multiple
an alternative to PCR and networks of and look for nucleotide
identify multiple nucleotide carbon atoms. single polymorphic sites
polymorphic sites in large Length and nucleotide in large strands of
strands on non-amplified diameter of polymorphism non-amplified DNA
DNA at relatively and low these tubes are which make
cost. 1nm and possible to
1-100nm in detect whether
length. an
individual has

39
 a high-risk or
low-risk
configuration
for
developing the
processes that
lead to cancer.
7. Metallic Nano particles  Gold By attaching  Gold nanoparticles are
Nanoparticles of various nanoparticles monoclonal not toxic to human
metals have been made yet conjugated to antibodies cells.
silver and gold anti-epidermal (mAbs), which  Economic as it
nanoparticles are of prime growth factor can requires a simple,
importance receptor (anti- recognize a inexpensive
for biomedical use EGFR) mAbs specific cancer microscope and white
specifically and cell, to gold light.
homogeneously nanoparticles  The results are
bind to the or instantaneous.
surface of the nano-rods the  Highly sensitive
cancer cells ―heating
with 600% phenomenon‖
greater affinity can be used in
than to the cancer
noncancerous detection. This
cells.
acoustic signal
 This specific
gives valuable
and
information
homogeneous
about the
binding is found
presence of
to give a
cancer cells
relatively
sharper surface
plasma
resonance
(SPR)
absorption

8. Nanoshells  Nanoshells have Once the  Increased efficacy of

a core of silica cancer cells the therapeutic
and a metallic take them up, treatment.
outer layer. by applying a
These can be near  Minimal set of side
linked to infrared light effects.
antibodies that that is
can recognize absorbed by
tumor cells the nanoshells,
(PSMA). it is
possible to

40
 create intense
heat that
selectively
kills the
tumor cells and
not the
neighboring
healthy cells.
9. Nanowires  These are They can  Capability to monitor
manmade detect the complexity of
Nano-sized sensing wires lie constructs; presence of biological processes
across a microfluidic made with altered genes
Channel carbon, silicon associated
and other with cancer
materials that and may help
have the researchers
capability to pinpoint the
monitor the exact
complexity of location of
biological those changes.
phenomenon.

Neuro-electronic Interfaces:
Neuro-electronic interfaces are a visionary goal dealing with the construction of
nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the
building of a molecular structure that will permit control and detection of nerve impulses by an external
computer. (Figure17)

Figure: 17:- NANODEVICE FOR NERVE REPAIR

41
 The computers will be able to interpret, register, and respond to signals the body gives
off when it feels sensations. The demand for such structures is huge because many diseases involve the
decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair
the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the
nervous system through neuro-electronic interface, problems that impair the system could be controlled so
that effects of diseases and injuries could be overcome.28
5. Cell repair machines
Using drugs and surgery, doctors can only encourage tissues to repair themselves. With molecular
machines, there will be more direct repairs. Cell repair will utilize the same tasks that living systems already prove
possible. Access to cells is possible because biologists can stick needles into cells without killing them. Thus,
molecular machines are capable of entering the cell. Also, all specific biochemical interactions show that
molecular systems can recognize other molecules by touch, build or rebuild every molecule in a cell, and can
disassemble damaged molecules. Finally, cells that replicate prove that molecular systems can assemble every
system found in a cell. Therefore, since nature has demonstrated the basic operations needed to perform
molecular-level cell repair, in the future, nanomachine based systems will be built that are able to enter cells,
sense differences from healthy ones and make modifications to the structure.(Figure 18)
Nanocomputers will be needed to guide these machines. These computers will direct machines
to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole
cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be
repaired. Finally, by working organ by organ, health is restored.28

Figure 18: CELL REPAIR MACHINES

42
6. Nanotechnology Clear Clogged Arteries
Heart patients are set to benefit from nanotechnology by using this technology for
clearing clogged and clogging arteries with the help of lasers. Nanotechnology coupled with laser
machines has also helped in reducing the side effects attributed with laser. In the case of laser, at times
remnants are left behind which tend to get hardened over a period of time.
Patients suffering from arterial conditions which are caused due to diabetes, smoking or
other conditions are subjected to this surgical procedure.44

Figure 19 : FOR CLEARING CLOGGED ARTRIES

Damaged arteries in extreme cases can lead to gangrene or debilitating conditions and
nanotechnology has been found out to be effective in clearing clogged arteries and minimize the side
effects of laser therapy.(Figure 19)

7. Bones to Be Grown with Nanotechnology

A new nanoscale biocomposite has been developed by scientists in Singapore which
will help in mimicking the extracellular matrix architecture. For this purpose electrospinning technique
was used for fabricating polycaprolactone/nanohydroxyapatite/collagen biocomposite nanofibrous
scaffolds which would offer mechanical support and lead to the growth of human fetal osteoblasts.44
This scaffold would be offering structural integrity within the body and ultimately
breakdown leaving behind the neo-tissue which will be instrumental in repairing the diseased tissues and
organs (Figure 20).

43
Figure: 20:- FOR GROWING BONES

44
 NANOTECHNOLOGY IN DENTAL SCIENCES

Nanodentistry is an offshoot of nanomedicine. Application of nanomedicine to dentistry

has lead to the emergence of a branch of science called Nanodentistry. Development of ―Nanodentistry‖ will
make possible the maintenance of near-perfect oral health through the use of nanomaterials, biotechnology
including tissue engineering and nanorobotics. The nanorobotic functions may be controlled by an onboard
nanocomputer that executes preprogrammed instructions in response to local sensor stimuli.46
Application of Nanodentistry can be categorized as
 Nanodentistry as bottom –up approach
 Nanodentistry as top-down approach

Nanodentistry as bottom –up approach

1. Inducing Anesthesia (Local anesthesia)
2. Hypersensitivity Cure
3. Tooth Repair
4. Nanorobotic Dentifrice (dentifrobots)
5. Orthodontic Nanorobots
6. Dental durability and cosmetics
7. Photosensitizers and carriers
8. Diagnosis of oral cancer
9. Treatment of oral cancer6
Nanodentistry as top-down approach
1. Salivary diagnostics powered by nanotechnologies
2. Nanotechnology for dental composites (Nanocomposites)
3. Nanotechnology for glass ionomer cement
4. Nano-Ceramic technology
5. Nanotechnology for impresion Materials
6. Nano adhesives
7. Nano needles
8. Nano bone replacement materials.6

45
 NANOTECHNOLOGY IN DIAGNOSTIC SCIENCE

Salivary diagnostics powered by nanotechnologies

The ability to monitor health status, disease onset and progression, and treatment outcome
through noninvasive means is a highly desirable goal in health care promotion and delivery. Oral fluid is a
perfect medium to be explored for health and disease surveillance. Specific biomarkers associated with a
health or disease state and the development of technologies that can discriminate between the biomarkers was
identified.47
A recent initiative of the National Institute of Dental and Craniofacial Research has
created roadmap to achieve these goals through the use of oral fluids as the diagnostic medium to scrutinize
the health and/or disease status of patients. This is an ideal opportunity to optimize state-of-the-art saliva-based
biosensors for salivary biomarkers that discriminate between diseases.47

Oral Fluid NanoSensor Test

The envisioned product is called the Oral Fluid NanoSensor Test (OFNASET). The
OFNASET is a handheld, automated, easy-to-use integrated system that will enable simultaneous and rapid
detection of multiple salivary protein and nucleic acid targets .This salivary biomarker detector can be used in
the office of a dentist or another health care provider for point-of-care disease screening and detection.

NANOTECHNOLOGY FOR RESTORATIVE DENTISTRY

1. NANOCOMPOSITE
One of the most significant contributions to dentistry has been the development of resin -
based composite technology. Adhesively bonded composites have the advantage of conserving sound tooth
structure with the potential for tooth reinforcement while at the same time providing a cosmetically acceptable
restoration. However, no composite material has been able to meet both the needs of posterior Class 1 or II
restoration and the superior esthetics required for anterior restorations. Nano-composite dental filling material
is a material that can be used in all areas of the mouth with superior polish (typical of microfills), as well as
excellent mechanical properties suitable for high stress - bearing restorations (typical of hybrid composite).
Nanocomposites consists of Nanofiller particles. Nanofiller particles may be of two types 48
a. Nanomeric, or NM
b. Nanoclusters or NCs

46
 Nanomeric (NM) particles are monodisperse nonaggregated and nonagglomerated silica
nanoparticles which is treated with 3-methacryloxypropyltrimethoxysilane, or MPTS. MPTS, a bifunctional
material so known as a coupling agent, contains a silica ester function on one end or bonding to the inorganic
surface and a methacrylate group on the other end to make the filler compatible with the resin before curing to
prevent any agglomeration or aggregation. MPTS also allows chemical bonding of the NM filler to the resin,
matrix during curing. Average particles size is 5-75nm.48
Nanoclusters (NCs) particles- The primary particle size of this NC filler ranges from 2 to 20
nm, while the spheroidal agglomerated particles have a broad size distribution, with an average particle size
(APS) of 1 µm.(Figure 21)
NC particles are fundamentally different from hybrid filler particles. Hybrid fillers, typically, are
large, dense particles of an average size of about 1 µm. These particles cannot be further subdivided under
normal abrasive forces in the mouth. Similar remarks apply to microhybrids, which are only slightly smaller
than hybrids in average particles size.
By contrast, the nanosized primary particles in the NCs wear by breaking of individual primary
particles (rather than plucking out the larger secondary particles from the resin). Thus, the resulting surfaces
have smaller defects and better gloss retention.48

Figure 21: NANOMERIC PARTICLES & NANOCLUSTERS

47
 3M ESPE has two products which come under the category of nanocomposites: 3M
ESPE Filtek™ Z350 Universal Restorative and 3M™ ESPE™ Filtek™ Supreme Plus Flowable Restorative.
3M ESPE Filtek™ Z350 Universal Restorative is a visible-light activated, direct restorative nanocomposite
designed for anterior and posterior restorations. 3M™ ESPE™ Filtek™ Supreme Plus Flowable Restorative is
a low viscosity, visible light-cured, radiopaque flowable restorative indicated for a variety of uses.48
The FST (Filtek Supreme Translucent shades) and FSS (Filtek Supreme Standard
shades) nanocomposite use combinations of NM or (nanomeric) particle and NC or (nanoclusters) fillers in
optimized ratios for desirable performance ( Figure 23). The NM particles in these formulations fill the
interstitial spaces between the clusters. The resultant surface, thus, is densely packed with fillers. The FST and
FSS materials consequently display high polish retention after toothbrush abrasion. When these materials
undergo toothbrush abrasion, only nanosized particles are plucked away, leaving the surfaces with defects
smaller than the wavelength of light. The visual appearance retains a high gloss and is consistent.48
Compressive and diametral tensile strengths of the nanocomposite (FSS and FST) are
equivalent to or higher than those of the other composites. The flexural strength and fracture resistance of FSS
and FST is higher than that of other composites.
Both the standard and translucent formulations of Filtek Supreme nanocomposite show
very high gloss retention, at 95 percent; respectively, of the original value.48
Supreme Plus flowable restorative blends the strength and beauty of Filtek Supreme
Plus Universal restorative with the ―flow on demand‖ handling Filtek™ Supreme Plus Flowable Restorative is
used in

i. As Liner/base
ii. Direct restorative for Class III, V
iii. Minimally invasive preparations
iv. Pit and fissure sealant
v. Repair of indirect composite, porcelain and temporary acrylic crowns

The ability to create a nanocomposite with a very low opacity provides the ability to
formulate a vast range of shade and opacity options from the very translucent shades needed for the incisal
edge and for the final layer in multilayered restorations to the more opaque shades desired in the enamel, body
and dentin shades. The commercial material is available in three translucent shades, seven enamel shades, 13

48
body shades and seven dentin shades. This allows the clinician the flexibility to make a choice of using a
single shade or a multi-shade layering technique, depending on the clinical case in question.48
This describes the use of nanotechnology to make a dental restorative composite

system that offers high translucency, high polish and polish retention similar to those of microfills while

maintaining physical properties and wear resistance equivalent to several commercial hybrid composites.

Combinations of two types of nanofillers result in the best combination of physical properties.

With the combination of super esthetics, long - term polish retention and other

optimized physical properties, it is expected that this novel nanocomposite is a system that would be used for

all posterior and anterior restorative applications.48

Product Description of 3M ESPE Filtek Z350 Universal Restorative

3M™ ESPE™ Filtek™ Z350 XT Universal Restorative is a visible light-activated
composite designed for use in anterior and posterior restorations. All shades are radiopaque. A dental adhesive,
such as those manufactured by 3M ESPE, is used to permanently bond the restoration to the tooth structure.
The restorative is available in a wide variety of Dentin, Body, Enamel and Translucent shades. It is packaged
in syringes and single-dose capsules. Indications for Use Filtek Z350 XT restorative is indicated for use in:
• Direct anterior and posterior restorations (including occlusal surfaces)
• Core build-ups
• Splinting
• Indirect restorations (including inlays, onlays and veneers) 49
Composition
The resin system is slightly modified from the original Filtek™ Z250 Universal
Restorative and Filtek™ Supreme Universal Restorative resin. The resin contains bis-GMA, UDMA,
TEGDMA, and bis-EMA resins. To moderate the shrinkage, PEGDMA has been substituted for a portion of
the TEGDMA resin in Filtek Supreme XT restorative.
The fillers are a combination of non-agglomerated/non-aggregated 20 nm silica filler,
non-agglomerated/non-aggregated 4 to 11 nm zirconia filler, and aggregated zirconia/silica cluster filler
(comprised of 20 nm silica and 4 to 11 nm zirconia particles). The Dentin, Enamel and Body (DEB) shades
have an average cluster particle size of 0.6 to 10 microns. The Translucent (T) shades have an average cluster

49
particle size of 0.6 to 20 microns. The inorganic filler loading is about 72.5% by weight (55.6% by volume) for
the translucent shades and 78.5% by weight (63.3% by volume) for all other shades.49

Product Description Shades

The system is comprised of four opacities, listed here in decreasing order of opacity:
Dentin (most opaque), Body, Enamel and then Translucent (very transparent). The Translucent shades are very
clear. The Enamel shades have opacity similar to tooth enamel. The Body shades are slightly more opaque,
less translucent than the Enamel shades to enable use in single shade restorations. Dentin shades have the
highest opacity. In multi-shade restorations, the Dentin shades are used to replace the more opaque dentin
tooth structure, alter underlying dentin color and block shine-through in anterior restorations.
The shade system is based on the VITAPAN Classical shade system with the following
exceptions: For bleached teeth: White Dentin, Body and Enamel (WD, WB, WE), Extra White Body and
Enamel (XWB and XWE). For cervical restorations: A6B and B5B Translucent shades: Clear, Blue, Gray and
Amber.49
Poduct Profile of 3M ESPE Filtek Supreme Plus Flowable Restorative
3M™ ESPE™ Filtek™ Supreme Plus Flowable Restorative is a low viscosity, visible
light-cured, radiopaque flowable restorative indicated for a variety of uses including liner/base, direct
restorative for Class III ,V and minimally invasive preparations, pit and fissure sealant and repair of indirect
composite, porcelain and temporary acrylic materials. Filtek Supreme Plus flowable restorative blends the
strength and beauty of Filtek Supreme Plus Universal Restorative with the ―flow on demand‖ handling of
3M™ ESPE™ Filtek™ Flow Flowable Restorative.49
Using the nanofiller technology of Filtek Supreme Plus universal restorative and the
rheology modifier of Filtek Flow flowable restorative, 3M ESPE has developed an esthetic flowable
restorative with excellent wear and polish properties and handling optimized for a variety of indications.49

Product Features
• Packaged in 2, 2g syringes.
• Directly dispensed through pre-bent disposable dispensing tips.
• Available in 12 shades that correspond to the shades offered with Filtek Supreme Plus
Universal Restorative: –
A1, A2, A3, A3.5, A4

50
 B1, B2
C2
D2
OA3
W, XW
Filtek Supreme Plus flowable restorative is incrementally placed and cured using a 400-500nm visible curing
light. The recommended maximum depth per increment and cure time is 2.0 mm for 20 seconds for all shades
except OA3 (2mm for 40 sec). These cure times can be reduced by onehalf when using the Elipar™ FreeLight
2 LED Curing Light.49
Indications for Use:-
• Class III and V restorations
• Restoration of minimally invasive cavity preparations (including small, non stress
bearing occlusal restorations)
• Base/liner under direct restorations
• Repair of small defects in esthetic indirect restorations
• Pit and fissure sealant
• Undercut blockout
• Repair of resin and acrylic temporary materials. 49
Composition:-
Resin:-
Filtek™ Supreme™ Plus Flowable Restorative is formulated with the methacrylate resin monomers
Bis-GMA, TEGDMA and Bis-EMA. Filtek Supreme Plus flowable restorative also contains a dimethacrylate
polymer that modifies the rheology of the material and provides a ―flow on demand‖ handling characteristic
allowing the material to flow under pressure, yet hold its shape after placement until light cured. A
photoinitiator component allows for light-curing when exposed to visible light in the 400-500 nanometer
range.49
Filler:-
The filler in Filtek Supreme Plus flowable restorative is a combination of:
• 75nm diameter non-agglomerated/non-aggregated silica nanofiller
• 5-10nm diameter non-agglomerated/non-aggregated zirconia nanofiller

51
 • Loosely bound agglomerated zirconia/silica nanocluster, consisting of agglomerates
of 5-20nm primary zirconia/silica particles. ( Figure 22)
The cluster particle size range is 0.6 to 1.4 microns. The inorganic filler loading is approximately 65%
by weight (55% by volume).49

FIGURE 22: NANOCLUSTERS & ZIRCONIA FILLER

52
Figure 23:- COMMERCIALLY AVAILABLE NANO COMPOSITES

53
Artiste™ Nano Composite System

Figure 24: NANO GLASS IONOMER CEMENT WITH DISPENSER

54
NANOTECHNOLOGY FOR GLASS IONOMER CEMENT

Composites have provided for an esthetic restorative; however a number of problems

are associated with using dental composites, with the primary ones being polymerization shrinkage,
intolerance to moisture and lack of essential bonding to dentine and enamel. While great strides have been
made in development of bonding agents, even the use of bonding systems to bond resin based materials to
dentine have not been wholly successful and their adhesive forces do not always adequately counteract the
polymerization contraction of the composite resin. Glass ionomer materials have been developed to solve
problems existing in application of composite resin restoratives.50
Glass ionomers are required to meet physical, chemical, biological and esthetic
requirements, same as other materials used in the mouth. Requirements for use include adequate strength,
abrasion resistance, resilience, and dimensional stability during processing and subsequent use. To match the
appearance of the oral hard tissue being replaced, translucency or transparency is also required. In addition
good color stability, and resistance to oral fluids with which they are in contact, must exist.50
Nanotechnology was used in the development to provide some value added features not
typically associated with glass ionomer restorative materials. Generally glass ionomer restoratives can contain
a broad range of particle sizes. Filler particle size can influence strength, optical properties, and abrasion
resistance. By using bonded nanofillers and nanocluster fillers, along with FAS (fluoraluminosilicate) glass
newer type of GIC was formulated using nanotechnology along with its fluoride releasing property ( Figure
24).
Nano Light Curing Glass Ionomer Restorative
The world's first nano-glass-ionomer is Ketac™ Nano Light-Curing Glass Ionomer
Restorative (Figure 22). In a clinical evaluation, over 60% of the dentists who used Ketac™ Nano Light-
Curing Glass Ionomer Restorative in their practice rated the final overall esthetics the same or better than their
current composite restorative material.51

Composition:
Two part system
 Aqueous paste (acidic polyalkenoic acid, reactive resins and nano fillers)
 Non aqueous paste (FAS glass, reactive resins, and nano fillers)

55
 Filler content (69%)
 27% FAS glass (acid and free radically reactive)
 42% methacrylate functionalized nano fillers (acid and free radically reactive)
The filler content of the system consists of an acid-reactive fluoroaluminosilicate glass
(FAS) and contains a unique combination of two types of nanofillers and nanoclusters. While nanofillers are
primarily discrete, the nanocluster fillers are loosely bound agglomerates of nano-sized zirconia/silica that
appear as a single unit, enabling higher filler loading, radiopacity and strength. The filler loading is
approximately 69% by weight. The third necessary component for a glass ionomer restorative is water. This
combination of FAS glass, polyalkenoic acid and water in Ketac Nano restorative is responsible for the ionic
glass ionomer reaction that takes place slowly over time. The other components include polymerizable
methacrylate monomers and photoinitiators, allowing the dentist to cure on demand.51
The filler loading is approximately 69% by weight of which the relative proportions of the
two filler types(nanofillers and nanoclusters of zirconia/silica) are approximately 2/5 and 3/5 respectively. All
of the nano fillers are further surface modified with methacrylate silane coupling agents to provide covalent
bond formation into the free radically polymerized matrix. The FAS glass is radiopaque, has an approximate
particle size of less than 3 µ (average particle size approximately 1 µ), and provides the basis for the glass
ionomer reaction and extended fluoride release in the presence of water and a polycarboxylic acid functional
polymer.51
Cure and Setting reactions

 Light curing (required)

 Long term glass ionomer reaction (water, glass ionomer filler, polyacid, monomers,

initiators)51

 GIC Nano Primer

Figure 25: GIC Nano Primer

56
 Nano primer is a one part, visible light-cure liquid specifically designed for use with GIC
Nano restorative.( Figure 25). It is comprised of the Vitrebond copolymer, HEMA, water, and photoinitiators.
The primer is acidic in nature. Its function is to modify the smear layer and adequately wet the tooth surface to
facilitate adhesion of Nano restorative to the hard tissue. In use, Nano primer is applied to the surface for 15
seconds, and air dried. The primer is then light cured for 10 seconds. Adequately air drying followed by light
curing of the primer before placement of GIC Nano restorative provides adhesion to tooth structure.

Ketac Nano is an ideal alternative esthetic glass ionomer solution for everyday dentistry.

Advantages of this material are:

 Superb polish: In-vitro testing results show Ketac Nano restorative has higher initial
polish than other glass ionomer restorative materials. 50
 Excellent esthetics: Shades of Ketac Nano restorative were developed to match the shade
targets of Filtek™ Supreme Plus Universal Restorative. An Atomic Force Microscope (AFM) was
used to compare the surface smoothness of four restorative dental materials ;Ketac™ Nano Light-
Curing Glass Ionomer Restorative, a composite material (Tetric EvoCeram®) and two competitive
resin-modified glass ionomers (Fuji II™ LC and Fuji Filling™ LC). After polishing, Ketac™ Nano
Light-Curing Glass Ionomer Restorative showed higher gloss and smoother surfaces than two
competitive resin-modified glass ionomer restorative materials. The gloss reflectance or polish
showed Ketac™ Nano Light-Curing Glass Ionomer Restorative having superb polish compared to
Fuji II LC and Fuji Filling LC. Results illustrate improved esthetics and reduced surface
roughness.50
 Higher wear resistance: Restorations made with Ketac™ Nano Light-Curing Glass
Ionomer Restorative looked great and performed well in abrasive environments. When tested
against competitive resin-modified glass ionomers, Ketac Nano restorative shows a higher wear
resistance, making it an ideal glass ionomer solution in posterior applications. 51
 It is faster, easier to mix and dispense. Ketac™ Nano Light-Curing Glass Ionomer
Restorative paste/paste formula can be used in a dispenser to make it faster and easier to dispense. 50
This product meets a Wide Range of Clinical Indications:
 Primary teeth restorations
 Transitional restorations

57
  Small Class I restorations
 Sandwich restorations
 Class III and V restorations
 Core build up

PHYSICAL PROPERTIES

1. Compressive Strength:-

Shown graphically in Figure 26 are compressive strength values for various

conventional, and resin modified glass ionomer restorative materials. Ketac™ Nano restorative has a higher

compressive strength compared to most other glass ionomer restorative materials.50

Figure 26: Graph showing compressive strength values for various conventional, and

resin modified glass ionomer restorative materials.

2. Diametral tensile strength

It is measured using a similar test method. Forces are applied to the sides of the sample until

fracture occurs. The diametral tensile strength of various materials is shown in Figure 27.

58
 Figure 27: Diametral tensile strength of various materials

Ketac Nano Restorative diametral tensile strength is statistically greater than conventional
glass ionomers and comparable to other resin modified glass ionomer restoratives.50
1. Flexural Modulus
Historically, glass ionomers have the reputation of being a brittle material. Flexural modulus
is a method of defining a materials stiffness. The flexural modulus is measured by applying a load to a material
specimen that is supported at each end. A low modulus indicates a flexible material. As shown in Figure 28
conventional setting glass ionomers exhibit a higher flexural modulus than resin modified glass ionomers.
Ketac™ Nano Light Curing Glass Ionomer Restorative exhibits a lower modulus (less brittle) than the
majority of both resin modified and conventional glass ionomers.50

Figure 28: Flexural modulus of conventional GIC Vs RMGIC

59
2. Flexural Strength:-

Flexural strength is determined in the same test as flexural modulus. Flexural strength is the
value obtained when the sample breaks. This test combines the forces found in compression and tension. In
Figure 29 the data indicates that flexural strength of glass ionomers can vary. The flexural strength of Ketac
Nano Restorative is comparable to Vitremer.50

Figure 29: Flexural Strength of different types of GIC’S

3. Microleakage:-

Microleakage studies were conducted by Dr. Tantibirojn from the University Of Minnesota
Dental Research Center for Biomaterials and Biomechanics (MDRCBB). Restorations were placed in
extracted human teeth with margins in enamel and dentin using the manufacturer‘s instructions for use.
Samples were thermocycled from 5°C to 55°C for approximately 24 hours and then immersed in a dye
solution for 24 hours. ( Figure 30). Teeth were removed, sectioned and measured using the following scale:
0 = no leakage
1 = less than one-third
2 = one third to two-thirds
3 = greater than two-thirds but within surrounding wall
4 = involve axial wall. 50

60
 Figure 30: Microleakage comparing Ketac Nano restorative to another leading resin

modified glass ionomer were comparable at the enamel and dentin interface.

4. Fluoride Release:-
Fluoride release is measured in-vitro in buffer solutions using a fluoride ion specific electrode.
In (Figure 31) Ketac™ Nano Light Curing Glass Ionomer Restorative shows a high fluoride release.
Additionally, but not shown here, in-vitro tests showed Ketac Nano restorative has the ability to recharge the
fluoride release after application of a topical fluoride source.50

Figure 31: Fluoride release of different types of GIC’s

61
5. Dentin and Enamel Adhesion:-
One of the most important characteristics of glass ionomer materials is their ability to
adhere chemically to mineralized tissues negating the use of an traditional etch, prime and bond system
typically used for composites. Glass ionomer restoratives characteristically require a conditioner, or a primer,
such as Vitremer™ Primer to clean and adequately wet the prepped surfaces. Glass ionomers typically fail
cohesively within the ionomer and thus reported adhesion is not necessarily true bond strengths. However, the
glass ionomers have been shown to be highly retentive clinically. Therefore their use as effective restorative
materials should not be ruled out on the basis of in-vitro bond strength data.50
MANIPULATION:-
Helpful Hints:
Shade Selection:-
Ketac™ Nano Light Curing Glass Ionomer Restorative shades are based on the Filtek™
Supreme Plus Universal Restorative System. There is a selection of eight different shades; A1, A2, A3, A3.5,
A4, B2, C2, and Blue. As with composite restorative systems, shade selection for an esthetic restoration should
be made with teeth fully wet. For core buildups, while any shade could be used, a contrasting color to tooth
structure such as the blue shade is sometimes preferred by dentists. 50

Priming:-
Ketac™ Nano Primer is quite a fluid so it should be dispensed into a well rather than onto a
pad. It is applied to both enamel and dentinal surfaces for 15 seconds. Keep the prepared tooth surfaces wet
with the primer for the full application time. Scrubbing the surface with the primer is not necessary. The
primed surface will appear shiny after drying and light curing. Using the Ketac Nano primer as instructed is
critical to achieving adhesion of Ketac Nano restorative to tooth structure. Primer use must not be eliminated
from the procedure. 50

Dispensing:-
Ketac Nano restorative was designed to be dispensed and mixed with equal volumes of each
paste in a ratio of 1.3/1.0. Dispensing two clicks from the Clicker™ Dispenser should provide an adequate
amount of material for most restorative filling applications. This is a guideline, and the user will need to
determine appropriate amounts for specific applications as they become familiar with the product. In the

62
unlikely event the dispensed pastes appear to be of uneven volume, the dose should be discarded. When
replacing the cap be sure an audible ―click‖ is heard to assure a tight fit.50

Mixing:-
The user must mix both pastes together for 20 seconds using a cement spatula. (Figure 32).
Paste may appear homogenous in less than 20 seconds, however less than 20 seconds of mixing may effect
some of the features and benefits of Ketac™ Nano Light Curing Glass Ionomer restorative, such as esthetics.50

Figure 32: Mixing of Ketac™ Nano Light Curing Glass Ionomer restorative

Placement:-

 We recommend placement of Ketac Nano restorative with a syringe system. Most of our

evaluators reporting on their experiences with the material found this placement technique to be

acceptable.

 Wetting the dental instruments used for shaping and contouring with Ketac™ Nano Primer may

prevent the glass ionomer from adhering to them. Another option is to use the fiber tip primer

applicator when manipulating the material in the prep.

 Ketac Nano restorative becomes relatively firm shortly after placement which can aid in shaping

the anatomy. However, do not exceed the 3 minute working time. Doing so may result in

deminished esthetics.

 Like most resin modified glass ionomers, Ketac Nano restorative cannot be placed in bulk,

layering of ≤ 2mm is required. ( Figure 33). Curing Ketac™ Nano restorative should be placed

63
 in 2mm increments or less, and light cured after each increment. An LED curing light will cure

all shades with a 20 second light exposure. Halogen lights are the same with the exception of the

darker A3.5 and A4 shades which require a 30 second exposure.50

Figure 33: Placement of Ketac Nano Light Curing Glass Ionomer restorative

Finishing:-

As with any finishing and polishing procedure with glass ionomer restorative materials it is

recommended that the surface be kept moist. Ketac Nano restorative can be polished with conventional

finishing and polishing instruments such as a diamond impregnated rubberized polishing system. A glaze such

as Vitremer™ Finishing Gloss may also be applied after polishing if desired.5

NANO-CERAMIC TECHNOLOGY

The Organically Modified Ceramic nano-particles comprise a polysiloxane backbone. The

chemical nature of the siloxane backbone is similar to that of glass and ceramics.

Methacrylic groups are attached to the backbone via silicon-carbon-bonds. These Nano-

Ceramic particles can be best described as inorganic-organic hybrid particles where the inorganic siloxane part

provides strength and the organic methacrylic part makes the particles compatible and polymerisable with the

64
resin matrix. The good resistance to micro-crack propagation might be related to the strengthening effect of the

nano-ceramic particles. Propagating cracks are either more often reflected or absorbed by the nano-ceramic

particles. (Figure 34) 52

Figure 34: Microcrack propagation in hybrid & Nano-Ceramic Restorative

COMPOSITION:- ( Figure 35)

 Methacrylate modified polysiloxane

 Dimethacrylate resin

 Fluorescence pigment

 UV stabilizer

 Camphorquinone

 Ethyl-4(dimethylamino)benzoate

 Barium-aluminium-borosilicate glass

 Methacrylate functionalised silicon dioxide nano filler.Iron oxide pigments and titanium oxide

pigments and aluminium sulfo silicate pigments according to shade.52

65
 Figure 35: Nanoceramic particles & Nanofillers.

Indications for use:-

Direct restorations of all cavity classes in anterior and posterior teeth.
Contraindications:-
Known allergy to methacrylate resins or any other of the components.

NANOTECHNOLOGY FOR ADHESION DENTISTRY

Nanosolution:-
Nanosolutions produce unique and dispersible nanoparticles, which can be added to various
solvents, paints and polymers in which they are dispersed homogeneously.53

66
 COMMERCIALLY AVAILABLE NANOSOLUTION

Figure 36: A protective sealant against abrasion

Seal&Protect™ offers a unique treatment to prevent cervical abrasion (Figure 36). This
light cured sealant protects exposed root dentine for at least 6 months. For the first time, the innovative Nano-
technology is used to reinforce the surface hardness of the exposed dentine. Seal&Protect™ is the first sealant
which protects the root dentine from toothbrush abrasion. Once applied to the root dentine, the polymerised
layer mechanically reinforces the dentine, increasing its surface hardness. This treatment is ideal for
preventing class V lesions.53
One of the active ingredients of Seal&Protect™ is triclosan, an antimicrobial agent, which
reduces plaque formation and fights caries associated bacteria. Unlike traditional antimicrobial substances,
triclosan does not exhibit negative side effects such as a bittertaste or discoloration.53

Additional benefits of Seal&Protect™

Seal&Protect™ continuously releases a highly effective amine fluoride, which gives added
protection to the tooth. In addition, by blocking the open dentine tubules on the root surface, Seal&Protect™
allows treatment of hypersensitive cervical areas. Seal&Protect™ allows patients to eat, drink and brush their
teeth immediately following application. In addition the translucency of the sealant offers the superior
aesthetics appreciated by patients.53

67
BONDING AGENTS

Figure 37: 5th generation bonding agent

 The nanofiller is extremely small, and is only about 7nm in diameter and hence it reaches
all the places the liquid components of Prime & Bond ®NT reaches.53
 The average dentinal tubule is about 0.8µm and the channels between the collagen fibrils
in acid conditioned dentine is about 20nm wide with a diameter of 5-10nm. The
nanofillers have therefore the perfect size to penetrate these channels to provide added
"Nano-retention". The filled adhesive is stronger than unfilled adhesive and when
infiltrated into conditioned dentine, it provides the polymeric toughness as well as
strength.53

FIGURE 38:- TOTAL-ETCH ADHESIVE

68
 The extremely small (5 nanometer) particles of nanofiller in Adper™ Single Bond plus
Adhesive are added in a manner that does not allow them to cluster together. The particles are stable and will
not settle out of dispersion.53
Advantages:
Higher dentine bond strength and better performance
 No shaking of bottle required since the nanoparticles are stable, neither do they cluster nor do they
settle out of-dispersion (in contrast, larger fillers tend to settle out of solution and such adhesives
require routine shaking before use).53
Thus, the use of nanotechnology in bonding agents ensures homogeneity and so the operator can
now have total confidence that the adhesive is perfectly mixed every time.53

NANO BONDTM

Figure 39: Nano Bond

BONDING AGENTS ( ADVANCES)

In the past, bonding materials required three steps: etching, priming and bonding, but the all-in-
one system integrates these three steps into one; hence, it is also called the "one-step" system. The G-Bond
(Figure 40) one-bottle system, which was launched recently by GC Corporation, eliminates mixing procedures
and is easy to handle in daily dental clinical practice.54
It has been shown that the adhesive strength of current all-in-one systems is lower than
that of two-step systems. G-Bond exhibits an adhesive strength of more than 40 MPa, which is comparable to

69
the adhesion of two-step systems to dentin. This indicates that G-bone has a satisfactory initial adhesive
strength.54
The interface formed by G-bond is totally different from that of the interface formed by
earlier bonding materials. The surface of the dentin is decalcified only slightly, and there is almost no exposure
of collagen fibers. This suggests that an extremely thin (300 nanometers or less) interface is formed and that in
this area, functional monomers contained in the bonding material react with hydroxyapatite at the "nano" level,
to form insoluble calcium. G-BOND's advanced formulation of phosphoric acid ester monomer, 4-MET
monomer, nano-filled particles, acetone and water solvent forms a nonconventional interface with the dentin.
This ―nano‖ level reaction produces an insoluble compound for a better bond that is less
likely to deteriorate from oral enzymes. The Nano Interaction Zone (NIZ) is characterized by little or no
exposure of collagen fibers and is extremely thin (only 300 nanometers).54
Therefore, the interface formed by G-bond is expected to be stronger and more durable
than that formed by other bonding materials. It would appear appropriate to name the interface exhibiting this
property, as a Nano Interaction Zone (NIZ), or a reacted layer at the "nano" level, as opposed to the traditional
hybrid layer application.
G-Bond is expected to exhibit good performance in daily dental clinical practice. G-Bond is
a one-bottle one-step adhesive system. Because all the components are contained in a single bottle, it is also
referred to as all-in-one adhesive system
Five different components are required in order to bond to the tooth structures, and in
particular, in order to bond to dentin which is hydrophilic.
These are
1) A functional monomer to remove the smear layer and make a space for the resin monomer to
infiltrate or demineralized.
2) A functional monomer to infiltrate the demineralized tooth surface and provide a direct connection
with the adhesive.
3) A resin monomer to link with the composite resin, which is hydrophobic, and promote cross-linking
between the resin monomers.
4) A solvent to evaporate water that is detrimental to adhesion from the adhesive interface.
5) An initiator to polymerize the resin monomer.

70
 In G-bond:
1) and 2) are 4-META and a phosphoric ester monomer.
3) UDMA.
4) Acetone.
5) Camphorquinone.
The new one-step adhesive system (G-Bond) produced a very thin (0.3 mm or less) layer which is
regarded as a chemical reacted layer. Therefore, this thin layer is called as the nano-interaction zone (N1Z).54

GC G-BOND
One Component, One Coat Bonding System for Light-Cured
Composites

FIGURE 40

NANOTECHNOLOGY FOR PROSTHETIC DENTISTRY IMPRESSION MATERIALS

The emerging fields of nanoscale science, engineering and technology the ability to work
at the molecular level, atom by atom, to create large structure with fundamentally new properties and functions
- are leading to unprecedented understanding and control over the basic building blocks and properties of
natural and man-made things.1
Impression materials Nanotech Elite H-D40,41 from the company Zhermack is available
with nanotechnology application. Here nanofillers are integrated in the vinylpolysiloxanes, producing a unique
addition siloxane impression material having added advantages of:

71
 1. One minute working time, 2 minute oral set time
2. Low contact angle of approximately 30° for accurate, reliable impressions in the oral
environment.
3. Outstanding tear strength ensures reliable impressions.
4. Minimized out gassing time for immediate pour of models

Nanotech Elite H-D + silicone (Figure 42) impressions formulation incorporates a

combination of organic polymers, inorganic particles and nano fillers (eg. Silica nanofillers). The result is
Silicone with increased fluidity, high tear resistance, hydrophilic properties, resistance to distortion and heat
resistance. The inclusion of nano particles has enabled Elite H-D+ to obtain a degree of fluidity completely
different from the initial viscosity. When pressure is exerted during impression taking an excellent reproduction
of infinitely small details is obtained.55,56
Elite H-D + has also been design to produce a snap set that consequently reduces errors
caused by micro movements. Elite H-D + is available in light fast, light regular set, medium and heavy
viscosities and is delivered in the new safety cartridges. Medium and heavy viscosity is also available in
polybags for machine mixing like the Pentamix™ 2 Automatic Mixing Unit (Figure 43) from 3M ESPE which
dispenses a completely homogeneous mix. 55,56

Features:
 Better flow
 Improved hydrophilic properties
 Fewer voids at margin and better model pouring
 Enhanced detail precision
 High tear resistance
 Resistance to distortion
 Heat resistance

72
NANO-COMPOSITE DENTURE TEETH
One of the most important physical properties of denture teeth used in the restoration of the
edentulous patient is wear resistance, as the material works to maintain the properly established vertical
dimension and chewing efficiency. Porcelain denture teeth have been considered the most wear resistant;
however, porcelain possesses a number of major disadvantages, including brittleness, lack of bonding to the
denture base, and difficulty in polishing."
Acrylic resin denture teeth are easier to recontour when the interocclusal distance is less
than ideal. Excessive wear of acrylic resin teeth has been a concern to both the patient and the dentist because
of unfavorable associated sequelae.55,
Acrylic denture teeth commonly undergo substantial attrition in relatively short periods of
time. In an effort to retain the acceptable clinical characteristics of acrylic resin teeth while gaining acceptable
wear resistance, several new types of resin denture teeth have been introduced. These include those made of
cross - linked acrylic and micro - filled composite resins. Nano filled denture teeth and conventional acrylic
teeth.
Knoop hardness values (KHN) ranged from 18.9 to 21.6 for cross -linked acrylic, 22.7 for
nano - composite, and 18.6 for conventional acrylic teeth. The wear depth values were 90.5 µm for the nano -
composite, 80.8 to 104.0 µm for the cross - linked acrylic, and 162.5 for conventional acrylic teeth. The worn
surface areas were 5.1 mm for the nano - composite, 4.4 to 5.7 mm for the cross - linked acrylic and 10.1 mm
for conventional acrylic teeth.55,56
New type of denture tooth, fabricated of nanocomposite resin, has recently, been, developed
as a highly polishable, stain and impact resistant material. It consists of a comonomer of urethane
dimethacrylate (UDMA) and methylmethacrylate (MMA). Polymethylmethacrylate (PMMA), and uniformly
dispersed nano - sized filler particles. Based upon the limited aspect of in vitro study results, and for the range
of representative materials tested, it appears that the nano - composite denture tooth sued in this study
possesses superior surface hardness and wear resistance compared to the conventional acrylic denture tooth.55
The new Veracia anterior and posterior teeth have been manufactured according to the
standards set by nature and offer exceptional aesthetics and a lively impression. For the first time prefabricated
teeth have an enamel layer of highly cross-linked, nano-filled composite. This has created a translucency and
surface quality previously unattained. The sculptured tooth shape and anatomical design of Veracia (Figure 41)
anterior and posterior teeth guarantee multifunctional purposes and provide an unlimited suitability for all

73
standard setup techniques of full and partial dentures. Shades available are : A1, A2, A3, A3.5, A4, B2, B3,
B4, C1, C2, C3, C4,D2, D3, & D4.56
It is indicated for Full denture prosthetics, Implant restorations, Telescopic restorations,
Attachment work and Cr-Co dentures.
Advantages
 Lively surface structure
 Matching the morphology of natural teeth
 Multifunctional use for all standard set-up techniques
 Economical arrangements of anterior and posterior teeth on both sides based on the
mirrored, anatomical design and the production with computer technology
 Extraordinary aesthetics
 Biocompatibility
 Limited variety of moulds for easier choice of anterior and posterior teeth
 Economical storage
 Excellent match with VITA* Classical shade system and
 Outstanding cost effectiveness55,56

Figure 41: Nano-composite Denture Teeth

FIGURE 41

74
 FIGURE42: Nanotechnology Impression Materials.

Figure 43: PENTAMIX UNIT

75
6) PROSTHETIC IMPLANT

The biomedical engineers have proven that cells attach better to metals with nanometer-scale
surface features, offering hope for improved prosthetic implants. Conventional titanium alloys used in
replacements are relatively smooth and the body often reacts to areas, as it would to any foreign invader, by
covering the parts with a fibrous tissue intended to remove the unwanted material. The fibrous tissue prevents
prostheses from making good contact with the body by getting between prosthetic devices and damaged body
parts. This in turn impedes their performance.57
By covering the implant materials with nanometer-scale bumps, they have shown that not only
can it keep the body form rejecting artificial parts but that the tiny bumps stimulate the body to regroup bone
and other types of tissue (Figure 44). Compared with titanium alloy covered in micron-sized bumps, about
60% more new cells are grown on the same alloy containing nanometer-scale features. Besides this the new
released alumina-zirconia nanocomposite, have a high resistance to crack propagation, and as a consequence
improving lifetime and reliability of ceramic joint prostheses.

FIGURE 44: Titanium coated Implant

With these nanocomposites it will be possible to extend the lifetime of implants up to a

minimum of 30 years, so contributing to improve the quality of life of a large number of patients. Further

surgical operations and consequently the suffering of people as well as the high cost of such operations will be

avoided.

76
NANOTECHNOLOGY IN SURGICAL INTERVENTION

INDUCING ANESTHESIA

One of the most common procedures in dentistry is the injection of local anesthetic,

involving long waits and varying degrees of efficacy, patient discomfort, and complications. Well-known

alternatives such as Transcutaneous Electronic Nerve Stimulation (TENS), Cell Demodulated Electronic

Targeted Anesthesia (CEDETA), and other transmucosal, intraosseous, or topical techniques are of limited

clinical effectiveness.29

To induce oral anesthesia in the era of nanodentistry, a colloidal suspension containing

millions of active analgesic micron-size dental nanorobots will be installed on the patient's gingiva.

After contacting the surface of the crown or mucosa, the ambulating nanorobots reach the

dentin by migrating into the gingival sulcus and passing painlessly through the lamina propria or the 1-3

micron thick layer of loose tissue at the cemento-dentinal junction. Upon reaching the dentin, the nanorobots

enter the 1-4 micron diameter dentinal tubule holes and proceed towards the pulp, guided by a combination of

chemical gradients, temperature differentials, and even positional navigation, all under onboard nanocomputer

control.29

Assuming a total path length of about 10mm from tooth surface to pulp, and a modest travel

speed of 100 microns/sec, nanorobots can complete the journey into the pulp chamber in 100 seconds

Once installed in the pulp and having established control over nerve impulse traffic, the

analgesic dental nanorobots may be commanded by the dentist to shut down all sensitivity in any particular

tooth that may require treatment. When the dentist presses the icon for the desired tooth on the handheld

controller display, the selected tooth immediately numbs (or conversely later, upon command, awakens). After

the oral procedures are completed, the dentist orders the nanorobots (via the same acoustic data links) to

77
restore all sensation, to relinquish control of nerve traffic, and to egress from the tooth by similar pathways

used for ingress, followed by aspiration.29

Nanorobotic analgesics offer greater patient comfort and reduced anxiety, no needles,

greater selectivity and controllability of analgesic effect, fast and completely reversible switchable action, and

avoidance of most side effects and complications.29

Nanoneedles:-

Suture needles incorporating nano sized stainless steel crystals have been developed.

Trade name: Sandvik Bioline, RK 91TM needles.

Nanotweezers are also under development which will make cell surgery possible in the near future.6

Figure 45: Surgical knife made from microstructured silicon with a Diamond
layered tip

NANOTECHNOLOGY IN PERIODONTAL THERAPY

LASER PLASMA APPLICATION FOR PERIODONTIA
When TiO2 particle sizes are reduced to nanoscale (20-50 nm diameter particles), and
present on human skin in the form of a gel-like emulsion, it has some interesting properties such that when
irradiated with laser pulses,these particles can be optically broken down with accompanying effects.58
a. Shock wave
b. Micro-abrasion hard tissue
c. Stimulation of collagen production

78
 Laser plasma is based on HPPL (High power plasma laser) combined with TiO2 nanotechnology and

has been proven effective in a number of dental treatments including:

1) Periodontal treatments. Most dental lasers in the market can do periodontal treatment of

gum diseases. Equilase-10, with radio frequency radiation. rate upto lOO Hz, pulse width of 100 microsecond

and energy per pulse up to 350 mJ, is far more powerful than the most powerful dental laser in the market.

With a dimension of 210 mm Wx463mm D x 380 mm H, it is very compact compared with other in the

market. Equilase-10 can treat gum disease alone, but with TiO2 nanotechnology it can be done cleaner and

quicker.58

2) Melanin removal. On the gums, it gives a lighter color and prettier gum appearance.

3) Incision of soft tissue without anesthesia

4) Cavity preparation. Equilase-10 combined with TiO2 nanotechnology can be used to prepare cavity

with no anesthesia required.

5) Cutting of enamel. Cutting speed of the enamel hard tissue comparable to using drills, but the result

is much cleaner, smoother, and no anesthesia required.

6) Dentine cutting. It results in rapid cutting of dentine.5

PLASMA LASERS FOR PERIODONTAL TREATMENT

Figure.
46

79
Nano Bone Fibres59
These have a tensile strength 100 times that of steel.
Polyphosphazene Nanofibers for Biomedical Application. These are assuming great interest in
local drug delivery system because of their superior properties (Figure 47)

Figure 47: POLYPHOSPHAZENE NANOFIBERS

Periodontal Bone Grafts

With both micro-porosity and nano-porosity, SynthoGraft has a greater surface area compared
to other synthetic bone grafting materials, allowing for ideal bone regeneration.59 (Figure 48)

Bone replacement materials

Hydroxyapatite nanoparticles used to treat bone defects are;
 Ostim ® (osartis GmbH Germany) HA.
 VITOSS ® (orthovita Inc, USA) HA+ TCP.
 NanOssTM (Angstrom Medica ,USA) HA.6

80
 Fig.ure 48: PERIODONTAL BONE GRAFT

BIOMIMETIC DENTAL IMPLANTS

Modifying the surface characteristics of the implant can promote migration of mesenchymal
cells to the implant surface, enhance attachment and proliferation of these cells, and in some instances,
stimulate osteoblastic differentiation. Some reportshave suggested that in designing a biomimetic implant one
should choose a surface texture of high roughness (presumably with some optimum value) and ensure a high
surface area, to optimize the ability of the implant to act as a ―carrier‖ for the planned biomimetic
coatings.60Such a design might also enhance osteoconductivity (the directed migration of osteoblast precursor
cells) and osteogenesis, and thereby improve long-term fixation of the implant through more effective
mechanical interlock at the bone-to-implant interface after osseointegration. Transforming an implant with this
preferred geometry into a biomimetic implant requires adding a coating of the growth factor (e.g., one of the
BMPs) or pharmacological agent of choice. This layer should preferably be thin enough not to alter the
underlying surface topography.
The addition of such coatings may require precoating of the implant with an appropriate
delivery vehicle for attachment and release of the active agent. Biodegradable ultra-thin layers of calcium
phosphate have also been proposed as potential carriers.60

NANOBIOPSY:
Biopsy is the surgical removal of tissue from a living subject to determine the presence or
extent of the disease. Biopsy is considered as a gold standard for definitive diagnosis. Recently, Robotic
Nanobiopsy has been developed by researchers which is a nanotechnology based tool. This system takes
samples of living cells without killing them. It uses a glass nanopipette of 50- 100 nm in diameter to pierce the
81
cell membrane to extract a volume of 1% of cell and is based on a customized Scanning Ion Conductance
Microscope (SICM). The tip is so fine that it causes minimal cell destruction. Researchers have used this
technique to extract and sequence RNA from individual human cancer cells and mitochondria from human
fibroblasts and sequence the mitochondrial DNA. It can also be used to deliver material into cells, opening up
ways to re-program diseased cells. It is a versatile platform for anyone trying to understand what is happening
inside the cell. Biopsy can be taken from a living cell and we can go back to the same cell multiple times over
a couple of days without killing it.61

NANOTECHNOLOGY IN DENTAL BIOFILMS:-

Nanotechnology is a promising field of science which offers better insight into the spatial
relationship between different species and how their diversity increases over time. Nanotechnology can guide
our understanding of the role of interspecies interaction in the development of bio-film. The contribution of
modern technology in the field of oral microbiology started with the detection of cultivable as well as
uncultivable bacteria by examining bacterial 16 sRNA and DNA.The spatial distribution of different oral
bacteria within the plaque has been revealed by fluorescent in situ hybridization.
The metagenomic project for oral microbial flora will reveal the metabolic genes and
virulence factors of oral microbes. Nanotechnology has been used to study the dynamics of
demineralization/remineralization process in dental caries by using tools such as atomic force microscopy
(AFM) which detect bacteria induced demineralization at an ultrascopic level. Using AFM, the correlation
between genetically modified Streptococcus mutans and nanoscale morphology has been assessed.62
The nanoscale cellular ultrastructure is a direct representation of genetic modifications as
most initiate changes in surface protein and enzyme expression, where host- cell nutrient pathways and
immune response protection likely occur. The surface proteins and enzymes, common to S. mutans strains are
a key contributor to the cariogenicity of these microbes. Another nanotechnology application used so far is
16O/18O reverse proteolytic labeling to determine the effect of biofilm culture on the cell envelope proteome
of oral pathogen, Porphyromonas gingivalis which is linked to chronic periodontitis.62
A group of cell–surface located C-terminal domain family proteins including Rgp A, Hag A,
CPG 70 and PG99 increased in abundance in the bio-film cells. The other proteins which increased were
transport related proteins (Hmu Y and Iht B), metabolic enzymes (Frd AB) and immunogenic proteins
Chalmers et al. have applied quantum dots (QD) (semiconductor nanocrystals) based primary
immunofluorence for in vitro and in vivo labeling of bacterial cells and compared this approach with the

82
fluorophore based primary immunofluorescence. QD conjugates offered significant advantages with standard
epifluorescence microscopy. Excellent single cell resolution of both in vitro and in vivo biofilms can be
obtained.62
The photostability of QD conjugates enables micromanipulation of viable, spatially resolved
communities from the enamel chip surface. These retrieved multispecies communities can be reconstituted and
studied in an in vitro model, where the intimate mechanisms of cell-cell interrelationships can be discovered.
Old culture techniques for detection and quantification of cariogenic bacteria in plaque or saliva sample are
slow and can only detect cultivable bacteria.
New antibody or nucleotide based bacterial detection techniques have been developed for
detection of cariogenic bacteria.62
Nanotechnology can further enable us to detect both cultivable bacteria and non cultivable with
the help of nanochip.Similarly plaque acidity which is a good index for monitoring tooth demineralization, can
be monitored using a microscale planer pH sensor. Application of nanotechnology to this prototype will
further reduce the size of the sensors and make the device more user friendly to both the patients and
clinicians. Nanotechnology can be used to selectively remove cariogenic bacteria while preserving the normal
oral flora in a more targeted and proactive approach to dental caries than the conventional operative dentistry.
Several ongoing research projects (e.g. enhanced active vaccination or passive vaccination, bacterial
replacement, targeted antimicrobial therapy) provide new directions in the treatment of dental caries. 62
A new silver nanotechnology chemistry has proven to be effective against biofilms. Silver
works in a number of ways to disrupt critical functions in a micro-organizm. For example it has a high affinity
for negatively charged side groups on biological molecules such as sulphydryl, carboxyl, phosphate and other
charged groups distributed throughout microbial cells. Silver attacks multiple sites within the cell to inactivate
critical physiological functions such as cell wall synthesis, membrane transport, nucleic acid (RNA and DNA)
synthesis and translation, protein folding and function and electron transport.
For certain bacteria as little as one part per billion of silver may be effective in preventing cell
growth. Recent studies show that ionic plasma disposition silver antimicrobial nanotechnology is effective
against pathogens associated with bio- films including E.coli , S.pneumoniae, S.pneumoniae, S.aureus and
A.niger. Hence, local nanoscale characterization of cellular ultrastructure and functional properties is an
important focus for probing cariogenic nature of oral microbes.62

83
 PREVENTIVE ASPECTS OF NANOTECHNOLOGY IN DENTISTRY

Caries-Preventive Nanofillers In Restorative Materials:-

Secondary caries and restoration fracture are still the main reasons for dental
restoration failure, thus limiting the longevity of (resin composite) restorations. To control caries-induced
demineralization at the resin composite-tooth interface, calcium and phosphate ion-releasing nanofillers have
been developed, such as nanoparticles of dicalcium phosphate anhydrous (112 nm I size) or of amorphous
calcium phosphate (116 nm in size). These additives enable the resin composite to release calcium and
phosphate when the pH is dropped down under in vitro conditions, providing caries-inhibiting properties.
Nanocomposites containing 40% nanoparticles of amorphous calcium carbonate have been shown to rapidly
neutralize a lactic acid solution of pH 4.0 by increasing the pH to 5.69 within 10 min. The mechanical
properties of the calcium- and phosphate-releasing experimental composites match those of commercial hybrid
composites.69
In addition, fluoride release from restorative materials has been considered to inhibit
tooth demineralization and caries development. The addition of CaF2 nanoparticles (50-60 nm) to resin
composites results in fluoride release similar to or even higher than that from commercial resin-modified glass-
ionomer materials. Nano-CaF2-containing composites with high flexural strength and sustained fluoride
release may have the potential to reduce restoration fracture and secondary caries. Recently, nanocomposites
containing CaF2 and dicalcium phosphate anhydride, which can release F, Ca, and PO4 ions for precipitation
of fluoroapatite and potential caries inhibiting capabilities, have been formulated with sufficient mechanical
properties.69
Most recent developments are novel nanocomposites which contain antibacterial
agents, such as chlorhexidine (10%) and quaternary ammonium dimethacrylate (7%) alone or in combination
with silver nanoparticles (0.028%), in addition to calcium and phosphate ion-releasing nanofillers.
Incorporation of these antibacterial components into nanocomposites has been shown to yield antibacterial
capabilities, thereby reducing the biofilm colony-forming unit counts, the metabolic activity, and lactic acid
production of Streptococcus mutans biofilms under in vitro conditions. However, the effectiveness of all these
strategies for the control of demineralization processes still needs validation, on the one hand, by in vitro
studies focusing on the caries inhibiting potential of ion-releasing and antibacterial resin composites, as well
as by subsequent clinical studies, on the other.69

84
Biomimetic synthesis of enamel – repair of caries lesions with enamel-like
nanomaterials:-
Due to its non-regenerative nature, enamel is unable to heal and repair itself after
demineralization of the surface and subsequent cavitation. Biomimetic strategies for artificial enamel
formation might have the potential to repair enamel surface damage and increase the longevity of teeth.
Extensive in vitro investigations of apatite crystallization have been performed to mimic the formation of
hierarchically organized enamel-like nano- and microstructures using acellular nanotechnological approaches.
Different kinds of synthesis methods have emerged for the preparation of amorphous or crystalline
nanoparticulate hydroxyapatite. However, much more impressive than the synthesis of individual or
agglomerated apatite particles on the nano-scale does the manipulation of nanoparticles to form highly
organized structures resemble natural enamel. Potential mechanisms for formation of highly oriented
biomineralized structures include guided crystal growth on templates, the aggregation of nanocrystals by
organized attachment, or the assembly of inorganic nanoparticles mediated by organic scaffolds into
aggregated structures.69
Combinations of nano-sized mineral particles, nano-crystal pastes, or calcium phosphate ion
solutions with various biological additives or surfactants were adopted to form structures mimicking the
hierarchical nanostructure of dental enamel. The application of surfactants as reverse micelles or micro-
emulsions for the synthesis and self-assembly of nanoscale structures is one of the most widely used methods
in nanotechnology. This technology mimics the natural biomineralization process taking place during
formation of enamel by modifying of hydroxyapatite nanorods with surfactants, allowing the nanorods to self-
assemble into an enamel prism-like structure. However, the suspected biocompatibility of non-biological
surfactants strongly limits their clinical application. In addition, attempts to mimic the nano- and micro-
structure of tooth enamel in various hydrothermal conditions, including non-physiological temperature or
pressure, cannot be applied clinically.69
A very promising route to achieve the arrangement of apatite nanoparticles in complex-
oriented enamel-like materials is the process of self-organization induced by amelogenin. Amelogenin is the
major extracellular matrix protein in the development of natural dental enamel and was adopted for the growth
of biomimetic enamel-like apatite layers. Amelogenin promotes apatite crystallization and organization. Thus,
the natural enamel protein amelogenin has been used in vitro to control calcium and phosphate crystallization,
resulting in the growth of nano-sized rod-like apatite crystals. With this method, remineralization of the
etched enamel surface by formation of a mineral layer containing needle-like fluoridated hydroxyapatite

85
crystals with dimensions of 35 nm has been demonstrated. Follow-up studies revealed that self organized
microstructures, compositionally and morphologically similar to natural ones, are achieved in a slow and
precisely controlled constant crystallization system, adopting amelogenin under ambient conditions.69
More recently, an oriented amelogenin fluoridated needle-like hydroxyapatite layer
could be precipitated on etched enamel in vitro by the application of amelogenin and fluoride in a
calciumphosphate solution, indicating a synergistic interaction of fluoride and amelogen. However, synthesis
of enamel-like structures adopting amelogenin-based approaches needs from several days to weeks and thus is
not directly applicable in daily dental practice. Currently, a biomimetic approach has been implemented in
which single crystalline hydroxyapatite micro-ribbons were used as substitutes for amelogenin templates to
control HAP crystallization at biophysical conditions at 37°C. 69

86
 FUTURE SCOPE OF NANODENTISTRY

Future and scope of Nanodentistry

(Nanodentistry as bottom –up approach)

New treatment opportunities in Nanodentistry may include:

1. Major Tooth Repair
2. Tooth Renaturalization
3. Hypersensitivity Cure
4. Inducing anesthesia
5. Orthodontic nanorobots
6. Dental Durability and Cosmetics
7. Nanorobotic Dentifrice (dentifrobots)
8. Durability and appearance
9. Nano Floss
10. Photosensitizers and carriers
11. Diagnosis of oral cancer
12. Treatment of oral cancer6

1. Major Tooth Repair:

Nanodental techniques for major tooth repair may evolve through several stages of technological
development, first using genetic engineering, tissue engineering and tissue regeneration, and later growing
whole new teeth in vitro and installing them (figure 48).
Ultimately, the nanorobotic manufacture and installation of a biologically autologous whole
replacement tooth, including both mineral and cellular components - e.g., complete dentition replacement
therapy.29

87
 FIGURE 49:- MAJOR TOOTH REPAIR

2. Tooth Renaturalization.
Dentition renaturalization procedures may become a popular addition to the typical
dental practice, providing perfect methods for esthetic dentistry. This trend may begin with patients who desire
to have their old dental amalgams excavated and their teeth remanufactured with native biological materials.
But demand will grow for full coronal renaturalization in which all fillings, crowns, and other necessary 20th
century modifications to the visible dentition are removed, with the affected teeth remanufactured so as to be
indistinguishable from the natural originals.29
3. Hypersensitivity Cure
Dentin hypersensitivity is another pathologic phenomenon that may be amenable to a
nanodental cure. Dentin hypersensitivity may be caused by changes in pressure transmitted hydrodynamically
to the pulp. This is based on the fact that hypersensitive teeth have 8 times higher than nonsensitive
teeth.There are many therapeutic agents for this common painful condition that provide temporary relief ,but
reconstructive dental nanorobots could selectively and precisely occlude selected tubules in minutes, using
native biological materials, offering patients a quick and permanent cure.29
4. Orthodontic nanorobots

Orthodontic nanorobots could directly manipulate the periodontal tissues including gingiva,
periodontal ligament, cementum and alveolar bone, allowing rapid painless tooth straightening, rotating, and
vertical repositioning in minutes to hours, in contrast to current molar uprighting techniques which require
weeks or months to proceed to completion.29

88
5. Tooth Durability and Cosmetics
Tooth durability and appearance may be improved by replacing upper enamel layers with
covalently bonded artificial materials such as sapphire or diamond, which have 20 to 100 times the hardness
and failure strength (that is, the pressure that must be applied to cause a solid material to fail catastrophically)
of natural enamel or contemporary ceramic veneers, as well as good biocompatibility. 29 Like enamel, sapphire
is somewhat susceptible to acid corrosion, but sapphire can be manufactured in virtually any color of the
rainbow, offering interesting cosmetic alternatives (for example, iridescence) to standard whitening and
sealant procedures. Pure sapphire and diamond are brittle and prone to fracture if sufficient shear forces are
imposed, but they can be made more fracture resistant as part of a nanostructured composite material that
possibly includes embedded carbon nanotubes. 29

6. Nanorobotic Dentifrice (Dentifrobots)

Subocclusal-dwelling nanorobotic dentifrice delivered by mouthwash or toothpaste could patrol
all supragingival and subgingival surfaces at least once a day, metabolizing trapped organic matter into
harmless and odorless vapors and performing continuous calculus debridement. Properly configured
dentifrobots could identify and destroy pathogenic bacteria residing in the plaque and elsewhere, while
allowing the 500 or so species of harmless oral microflora to flourish in a healthy ecosystem.29
Used as a mouthwash containing full of smart nanomachines to identify and destroy pathogenic
bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem. The devices would
identify particles of food, plaque, or tartar, and lift them from teeth to be rinsed away (figure 49). Being
suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of
toothbrush bristles or the fibres of floss.29

FIGURE50: DENTIFROBOTS

89
7. Nanotech Floss
Ultra-thin, ultra-glide; completely non-shredding with excellent tensile strength.The unique
nano-structure of Dental Tape allows for the addition of flavors, and delivery of medications.29 (Figure 50)

FIGURE 51:- NANOTECH FLOSS

8. Photosensitizers and Carriers

Present on the surface of the target cell and when stimulated by UV light, they can give rise to
reactive oxygen species and thus will be lethal to the target cell.6
9. Diagnosis of oral Cancer
 NANOELECTROMECHANICAL SYSTEMS (NEMS)
Convert (Bio) chemical to electrical signal
 CANTILEVER ARRAY SENSORS
Ultrasensitive mass detection techonology:
10-12 Picogram– Bacteria
10-15 Femtogram– Virus
10-18 Attogram– DNA
 MULTIPLEXING MODALITY
Sensing large numbers of different biochemical simultaneously in real time.6

90
 Application:
 Diagnosis of diabetes mellitus and cancer
 Detection of bacteria, fungi, and viruses.6

10. Treatment of Oral cancer

 NANOMATERIALS FOR BRACHYTHERAPY
BrachySilTM (Sivida, Australia) delivers 32P, Clinical trial6
 DRUG DELIVERY ACROSS THE BLOOD-BRAIN BARRIER
More effective treatment of brain tumors, Alzheimer‘s, Parkinson‘s in development.6
 NANOVECTORS FOR GENE THERAPY
Non- viral gene delivery systems

11. Self cleaning and anti-bacterial mirrors

One major drawback of dental mirrors is their fogging due to patient breathing during
examination. Also, water sprayed from the hand piece and disseminated particles during drilling and
condensing the restorative materials as well as the saliva in the oral cavity contaminate the reflective mirror
surface and interfere with the vision of dentist. Impaired vision due to mirror contamination and interference
from debris, mist and sprays has always been problematic for dentists.
During years, many attempts have been made to overcome this issue such as manufacturing of
mirrors with air and water spray in the rim of the mirror surface that continuously siphon the water across the
reflective surface, spontaneously heated mouth mirrors that prevent accumulation of water or fogging of
mirrors, and mirrors with a rotor and centrifugal force that expel water or other materials on the reflective
surface. Another problem is the need for repeated autoclave sterilization of instruments.63
High temperature and pressure of autoclave can corrode the metals and decrease the quality
of dental instruments. The metal frame of the mirror is damaged by repeated sterilizations and decreases the
quality of mirror. One solution is to coat the mirror surface using nanotechnology. This method has some
advantages over others. Other methods are complex and for example there is a button at the end of the mirror
handle that needs to be pressed by the dentist to clean the mirror surface.63
However, mirrors coated with nano-scaled particles have an innate self-cleaning property and
do not require pressing a button or anything like that. To date, several nanometer scale materials have been

91
used to coat mirror surfaces. Some have used nanometer scale TiO2 on mirror surfaces. Others have used a
mixture of glass particles and air bubbles. A few others have coated mirror surfaces with nanopolymer
materials. The effect of coating the mirror surface with nanometer scale particles has been evaluated by several
researchers.63
Furthermore, it has been discussed that if TiO2 particles on the mirror surface are exposed to
UV light they can eliminate the bacteria present on the mirror surface.64
12. Regeneration of pulp cells
Traumatic dental injuries are often irreversible, underscoring the need for therapies that
protect dental pulp cells and enhance their regeneration. It was hypothesized that generation 5 poly amido
amine (PAMAM) dendrimers (G5), functionalized with fluorescein isothiocyanate (FL) and αVβ3- specific,
cyclic arginine-glycine-aspartic acid (RGD) peptides, will bind to dental pulp cells (DPCs) and modulate
their differentiation. Dental pulp cells and mouse odontoblast-like cells (MDPC-23) (±) treated with G5-FL-
RGD were analyzed via Western blot, RT-PCR, and quantitative PCR. Transcription of dental
differentiation markers was as follows: Dentin matrix protein (DMP-1), dentin sialoprotein (DSPP), and
matrix extracellular phosphoglycoprotein (MEPE) as well as vascular endothelial growth factor (VEGF) all
increased via the JNK pathway. Long-term G5-RGD treatment of dental pulp cells resulted in enhanced
mineralization as examined via Von Kossa assay, suggesting that PAMAM dendrimers conjugated to cyclic
RGD peptides can increase the odontogenic potential of these cells.65
In a study by, we hypothesized that generation 5 (G5) dendrimers, conjugated to a
commercially available, integrin-binding peptide composed of arginine-glycine-aspartic acid (RGD), would
modulate differentiation in dental pulp cells. RGD, a naturally occurring ligand, can be synthesized in a
cyclic motif to bind specifically to αVβ3 integrin receptors. 65
They found that G5-RGD, initially synthesized as a targeting platform, enhanced the
expression of differentiation markers in dental pulp cells, and that these markers were activated via the c-
Jun amino terminal kinase (JNK) pathway, leading to enhanced mineralization by dental pulp cells.65

92
NANOCOMPOSITE WITH ANTI-BACTERIAL EFFECT
Resin-based dental composites have been widely used in dentistry to restore decayed
teeth. These composites have sufficient flexural strength (from 80 to 140 MPa) and outstanding esthetics.
However, dental composite restorations have limited service life (average, 7 yrs) due to fracture of the
restoration itself or to secondary caries developed at the restoration margins caused by accumulation of
cariogenic biofilms. The subsequent replacement of restorations by drilling and filling in the United States
alone costs more than $5 billion annually. Strategies are needed to extend the service life of the dental
composite restorations by effectively inhibiting cariogenic biofilms and thus reducing secondary caries,
especially in high-caries-risk populations. Dental composites that can inhibit cariogenic biofilms while
maintaining their mechanical properties are highly desirable. 66
Chlorhexidine (CHX), with its broad-spectrum antibacterial activity and low cytotoxicity,
has been widely used in oral infection control as a mouthrinse, dental coating (Prevora®), and denture wash
and is considered a ―gold standard‖ for the evaluation of antimicrobial agents. CHX-containing dental
composites have been studied, and the CHX release rate has been controlled by the degree of cross-linking,
which also contributed to a balance between swelling induced by water sorption of hydrophilic composition
and polymerization shrinkage. 66
The presence of CHX, however, incurred detrimental mechanical or physical properties of
the composites, including decreased strength, porous surface, and increased water sorption. The main reason is
that CHX (a salt) is immiscible with dental monomers. It forms aggregates in the resin matrix of the
composite, andthe dissolution of CHX aggregates leads to the formation of a porous surface, which has poor
wear resistance. It also increases the potential for staining and bacterial biofilm accumulation. Therefore,
simply mixing CHX into a dental composite will produce an inferior material that does not meet the
requirements for dental applications. 6
Mesoporous silica nanoparticles (MSNs) with high pore volume and surface area have
attracted increasing attention as reservoirs to encapsulate and release disparate molecules including fenbufen,
silver, CHX, gene delivery system, etc. However, studies of applications of MSN in dental materials have been
rare. So far only one report has described the release of nitric oxide as an antibacterial agent from the dental
composite containing MSN modified by O2-protected N-diazeniumdiolate-based silanes. Two other reports
showed that a combination of MSN with non-porous fillers seems to increase the mechanical properties of the
composites. There are also major differences in the design and applications of MSN between dental
composites and other drug releasing materials or biomaterials.66

93
Nanomodification of MTA
White mineral trioxide aggregate (WMTA) (ProRoot, Dentsply Tulsa Dental, Tulsa, OK,
USA) has several advantages over other materials used in endodontics, including biocompatibility, good
sealing ability and antibacterial properties (Torabinejad et al. 1995). Despite these advantages, it has a long
setting time and low resistance to acid, which may prevent MTAsetting as well as increase its porosity. Mixing
MTA with an acidic solution such a 2% lidocaine HCl with an epinephrine concentration of 1 : 100 000
reduced the compressive strength of MTA in an acidic environment .67
Attempts have been made to improve the properties of WMTA by incorporating materials
into its structure. However, the physical and chemical properties are often affected adversely. Strontium salts
improve the bioactivity of bone substitute materials.67 Moreover, bioactivity is highly desirable for root-end
filling materials. Studies have shown that the smaller particle size and increased surface area of Portland
cement play an important role in physical and chemical properties, partly because of better and more rapid
hydration with lower porosity. 67
Final setting time of WMTA is more than 3 h .Initial setting time has been reported to be
approximately 40 min, which is not desirable when WMTA is used as a root-end filling material.
Microhardness has an inverse relationship with porosity. Therefore, WMTA with a higher microhardness value
has less porosity.Lower porosity is highly desirable for an impermeable rootend filling material.67
Studies have shown that environments with low pH values can adversely affect WMTA by
reducing microhardness and increasing microleakage. The effect of surface area of powder on properties of
WMTA has not been well documented. Incorporating various trace elements such as strontium on the physical
and chemical properties of MTA has not been elucidated. A new version of MTA (Nano) has been patented in
the USA and claimed to set faster with acceptable resistance to acidic environments by adding a small amount
of strontium and reducing its particle size.67

Nanotechnology for tooth regeneration

Nanotechnology has enormous potential in the field of dentistry. For example, tooth
regeneration is an important aspiration of the dental profession. The combination of tissue bioengineering
along with the development of genetically designed trigger nanoparticles, which are biomimetic with
mineralised tissues, is beginning to bearfruit in the manufacturing of in vitro tooth.68

94
 Regeneration of teeth can be divided into several specific areas:

• Regeneration or de novo formation of an entire, anatomically correct tooth;

• Regeneration of the root;
• Regeneration of dental pulp;
• Regeneration of dentin that may either act as reparative dentin to seal off an exposed pulp chamber
or as a replacement of current synthetic materials;
 Regeneration of cementum as a part of periodontium regeneration or for loss of cementum and/or
dentin resulting from orthodontic tooth movement.
 Regeneration of periodontium including cementum, periodontal ligament, and alveolar bone.
Regeneration or synthesis of enamel-like structures that may be used as biological substitute for
enamel.
 Re-mineralisation of enamel and dentin. For tooth regeneration, biomaterials have served primarily as a
scaffold for

(1) Transplanted stem cells and/or

(2) Recruitment of endogenous stem cells.68

It is indispensable for the regeneration of tooth root, tooth crown, dental pulp, or an
entire tooth. Nanomaterials, which mimic surface properties of natural tissues, are promising candidates for
improving traditional dental tissues engineering materials. 68

95
 HAZARDS OF NANOTECHNOLOGY

"Nanoscale science and engineering promise to be as important as the steam engine, the
transistor, and the Internet, and have the potential to revolutionize all other technologies," according to Neal
Lane, former science advisor to U.S. President Bill Clinton. "But that outcome is not guaranteed."70

Nanotechnology, the emerging science of creating incredibly miniscule microscopic

machinery and objects, seems beneficiary to many people. It provides solutions to many problems of mankind.
However, nanotechnology may not be flawless.

Billions and billions of dollars have already been given to the study of nanotechnology.
Items which are unbelievable to some have already been selling. Yet, tests have shown that nanotechnology
can function as venom to the communities we live in and nanoparticles are known to biomagnify in animal
organs. Scientists are also concerned about soil and plant life.

"The smaller the particles, the more toxic they become," explained V. Howard, a
University of Liverpool pathologist. The first of two studies to look for these dilemmas was a study sponsored
by NASA, the space agency which looks to take advantage of nanomaterials. In this study a scientist and his
partners transferred three types of nanotubes into mice. The nanotubes traveled to the lungs of the rodents. All
of the nanotubes had resulted in lung infections that get in the way with oxygen receiving and may end up to
lung disease what is known as granulomas. Each mouse got one contact with the nanotubes, but the wound got
awful leading to tissue death. Quartz fragments, considered by toxicologists as a poisonous substance, had less
dangerous reactions than the nanoparticles.71

Nanomedicine is a science that uses nanotechnology to maintain and improve human

health at the molecular scale. Current and potential applications of nanotechnology in medicine range from
research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering
procedures. Its advantage over conventional medicine lies on its size. Particle size has effect on serum lifetime
and pattern of deposition. This allows drugs of nanosize be used in lower concentration and has an earlier
onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a
specific location. Major efforts are underway however; very little attention is devoted to assessment of health
risks to human or to the ecosystem. Inhaled nanoparticles have already been related to lung injury.

96
 It is recognized that physico-chemical properties in conjunction with environmental factors
and stability of the nanomaterial all contribute to the overall toxicological responses. Nanotoxicological
information, currently insufficient, will be vital in aiding academia, industry and regulatory bodies in
elucidating the mechanisms of action, balancing its risk and benefit, thus maximizing the utility of these
materials in medicine without compromising public health and environmental integrity.72

Figure 51: Diseases Associated to Nanoparticle Exposure.

97
 CONCLUSION

Nanodentistry is said to be the future of dentistry wherein all procedures are performed
using devices based on nanotechnology. Nanorobots may take place of Dental assistant employment. Teeth
implant will be possible in just one single sitting using nanomedicine and biotechnology and that too with
ultimate correctness. Diagnoses will be done using smaller machine tools and nano devices. Such devices will
be capable to diagnose a problem and give solution shortest span of time. This all will happen within another
10-20 years from now.
Nanodentistry is also referred to as robotic dentistry which uses nanorobots.
Dentirobots will help destroy harmful bacteria on daily basis which will help in decreasing tooth decay,
cavities and gum problems. Tooth repair, orthodontics, sensitivity gum repair, cosmetic procedures, tooth
renaturalization etc. will become possible with this technological changes that come along Nanodentistry.
In future, dentist employment opportunities may demand a degree in nanorobotics. This
is going to be true soon. Nurse employments will demand know-how in handling nanomaterials and
nanorobotics. Dental assistant employment is going to become hi-tech in real sense when this all happens. For
inducing local anaesthesia dentist will instill millions of active micrometer sized dental nanorobots in the
patient‘s mouth.
These nanorobots will then reach the dentin, and enter the dentinal tubule holes to
proceed towards the pulp for further treatments. For orthodontic treatment orthodontic nanorobots will
manipulate the periodontal tissues which will allow a fast and painless tooth rotating, straightening, and
vertical repositioning in minutes.
Even natural tooth maintenance will become much easier as the appearance and
durability of teeth will be improved by replacing enamel layers with artificial materials which are much
stronger than the natural coating.
Making smaller machine tools, microscopic instruments and manufacturing tools such as
nano machines, nano robots, and nano devices is going to be the top most lucrative business in future. Dental
assistant employment will become as prestigious as the dentist himself.
There will be times when the dentist will not be present for the treatment and leave the
job to the assistant and the dentrirobots of his clinic. Dentirobots can identify and destroy pathogenic bacteria
from the plaque allowing harmless oral micro flora to survive in the ecosystem. Conventional tooth decay and
gingival disease are going to disappear when such dental hygiene will be maintained on daily basis.

98
 REFERENCES
1. Jhaveri HM Balaji PR .Nanotechnology: the future of dentistry. J Indian
prosthodont Soc 2005;5(1):15-17
2. Sahoo SK, Parveen S, Panda JJ. The present and future of nanotechnology in human
health care. Nanomed Nanotechnol Bio Med. 2007; 3:20-31.
3. Gorav S., Kamlesh V., Nidhi P. Nanodentistry-The future ahead. BF Univ Dent J 2010;
1:43-45.
4. Gordijn B. Nanoethics. From utopian dreams and apocalyptic nightmares towards A more
balanced view.
5. Binu NS, Varghese NO .Nanodreams in dentistry-A step ahead the Future! JIDA 2002;
173:299-303.
6. Saravana K.R, Vijaylakshmi Nanotechnology in dentistry. Indian Journal of Dent Res
17(2): 62-65, 2006.
7. Lu, G., Kaxiras, E.: Overview of multiscale simulations of materials. Handb. Theor.
Comput. Nanotechnol. 10, 1–33 (2005)
8. Introduction to Nanoscience, 2005
9. Dr Ananya Mandal, News- Medical.net Life Sciences and Medicine.
10. "Sunscreen". U.S. Food and Drug Administration.
11. Mitchnick, MA; Fairhurst, D; Pinnell, SR (1999). "Microfine zinc oxide (Z-cote) as a photostable
UVA/UVB sunblock agent". Journal of the American Academy of Dermatology 40 (1): 85–90.
doi:10.1016/S0190-9622(99)70532-3.
12. Heim, J; Felder, E; Tahir, MN; Kaltbeitzel, A; Heinrich, UR; Brochhausen, C; Mailänder, V; Tremel,
W; Brieger, J (21 May 2015). "Genotoxic effects of zinc oxide nanoparticles.". Nanoscale 7 (19):
8931–8.
13. Wang, B; Zhang, Y; Mao, Z; Yu, D; Gao, C (August 2014). "Toxicity of ZnO nanoparticles to
macrophages due to cell uptake and intracellular release of zinc ions.". Journal of nanoscience
and nanotechnology 14 (8): 5688–96.
14. Maureen R. Gwinn and Val Vallyathan. (2006) Nanoparticles: Health Effects—Pros and
Cons Environmental Health Perspectives. 114(12):1818- 1825.

99
15. Paul J. A. Borm and Wolfgang Kreyling. (2004) Toxicological Hazards of Inhaled
Nanoparticles- Potential Implications for Drug Delivery. Journal of Nanoscience and
Nanotechnology. 4(6):1-11.]
16. Journal of Interdisciplinary Dentistry / Jul-Dec 2011 / Vol-1 / Issue-2 T. S. V.
Satyanarayana, Rathika Rai.
17. www.apinanotronics.com/investors/glossary.asp
18. Abhilash M: Potential applications of Nanoparticles: International Journal of Pharma and
Bio Sciences V1(1)2010.
19. Sílvia S. Guterres, Marta P. Alves and Adriana R. Pohlmann: Polymeric Nanoparticles,
Nanospheres and Nanocapsules, for Cutaneous Applications: Drug Target Insights 2007:
2 147–157.
20. Uttam Kedar, Prasanna Phutane, Supriya Shidhaye, Vilasrao Kadam: Advances in
polymeric micelles for drug delivery and tumor targeting:
Nanomedicine:Nanotechnology, Biology and MedicineVolume 6, Issue 6, December
2010, Pages 714–729.
21. Manju Rawat, Deependra Singh, S. Saraf, and Swarnlata Saraf. (2006) Nanocarriers:
Promising Vehicle for Bioactive Drugs. Biol. Pharm. Bull. 29(9):1790—1798.
22. Maghraby GMM, Williams AC, Barry BW. Int J Pharm. 2000;196:63–74.
23. Redziniak G. Phathologie Bio. 2003;51:279–81.
24. Choi MJ, Maibach HI. Skin Pharmacol Physiol. 2005;18:209–19.
25. Alvarez-Román R, Naik A, Kalia YN, Guy RH, Fessi H. J Control Release. 2004a;99:53–62.
26. Upadhyay Y.; Current state and future perspectives of nanotechnology in dentistry;
International Organization of Scientific Research J Pharm 2013; 3: 68-71.
27. Nanomedicine. Google search. Website : http://www.nano-biology.net

28. www.wikipedia.org/wki/nanotechnology.

29. Freitas Jr R.A. Nanodentistry. JADA 2000 Nov; 131: 1559-66.

30. Rocco MC, Nanotechnology: convergence with modern biology and medicine. Curr Opin
Biotechnol. (2003) 3, 337-46.
31. Laurent Levy – The coming era of nanorobots: Recent articles compiled by Robert A. Freitas on
Medical nanomaterials, nanobiotechnology,or nanomedicine;Oct.2000

100
32. Silke Krol, Rutledge Ellis-Behnke, Piero Marchetti: Nanomedicine for treatment of
diabetes in an aging population: state-of-the-art and future developments;Journal of
Nanomedicine Nanotechnology,Biology and Medicine; September 2012Volume 8,
Supplement 1, Pages S69–S76.
33. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer disease: progress and
problems on the road to therapeutics. Science 2002;297:353-6.
34. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in
Alzheimer disease. Acta Neuropathol 2009;118:103-13.
35. Rensink AA, De Waal RM, Kremer B, Verbeek MM. Pathogenesis of cerebral amyloid
angiopathy. Brain Res Rev 2003;43:207-23.
36. Attems J, Jellinger KA. The overlap between vascular disease and Alzheimer disease—
lessons from pathology. BMC Med 2014;12:206.
37. Herrmann N, Chau SA, Kircanski I, Lanctôt KL. Current and emerging drug treatment
options for Alzheimer disease: a systematic review. Drugs 2011;71:2031-65.
38. Bana L, Minniti S, Salvati E, Sesana S, Zambelli V, Cagnotto A, et al. Liposomes bi-
functionalized with phosphatidic acid and an ApoEderived peptide affect aβ aggregation
features and cross the blood-brainbarrier: implications for therapy of Alzheimer disease.
Nanomedicine 2014;10:1583-90.
39. Re F, Airoldi C, Zona C, Masserini M, La Ferla B, Quattrocchi N, et al. Beta amyloid
aggregation inhibitors: small molecules as candidate drugs for therapy of Alzheimer
disease. Curr Med Chem 2010;17:2990-3006.
40. Matsuoka Y, Saito M, Lafrancois J, Saito M, Gaynor K, Olm V, et al. Novel therapeutic
approach for the treatment of Alzheimer disease by peripheral administration of agents
with an affinity to beta-amyloid. Neurosci 2003;23:29-33.
41. Andrea Masotti, , Mark R. Miller, Antonella Celluzzi, Lorraine Rose, et al :Regulation of
angiogenesis through the efficient delivery of microRNAs into endothelial cells using
polyamine-coated carbon nanotubes : Journal of Nanomedicine: Nanotechnology,
Biology and Medicine; Volume 12, Issue 6, August 2016, Pages 1511–152.
42. www.nanoshop.com
43. Otilia MK, Rubinstein I .Role of nanotechnology in targeted drug delivery and imaging: a
concise review.Nanomedicne :Nanotechnology,Biology, and Medicine 2005;1:193-212.

101
44. http://advancednano.blogspot.com/2006_06_01_archive.html
45. Pramod B, Sujata S, Dayananda BC, Nagaraju K, Saleem Shaikh: Nanosystems: Role In
Oncology - An Overview: Indian Journal of Dental Sciences. March 2013 Issue:1, Vol.:5.

46. Nanodentistry- The Future. Ref: JADA Oct.2000.website:

http://www.healthmantra.com/ypb/jan01/nano

47. Wong DT. Salivary diagnostic powered by nanotechnologies, proteomics and genomics
.JADA; 137:313-321.

48. Mitra SB, Wu D, Holmes BN. An application of nanotechnology in advanced dental

materials. Am Dent Assoc 2003; 134:1382- 1390.
49. 3M ESPE Filtek™ Z350 XT Universal Restorative System and 3M ESPE Filtek Supreme
Plus Flowable Restorative :Technical product profile.
50. Ketac™ Nano Technical Product Profile
51. Ketac™ Nano Light-Curing Glass Ionomer Restorative.
http://solutions.3m.com/wps/portal/3M/en_US/3M-ESPE/dental-
professionals/products/category/direct-restorative/ketac-nano/
52. Ceram x nanoceramic restorative : scientific compendium
53. www.Dentsply.com
54. Hidehiko Sano et al. Indications for a new keyword in adhesion. Available from URL:
http://www.gc dental. Co. jp
55. Suzuki S. In-vitro wear resistance of nanocomposite denture teeth. JPD 2004 Dec; 13(4):
238-43.
56. Veracia Nanocomposite Denture Teeth: Google search. Website:
http://www.shofu.de/deutsch/deutsch/produkte/ansicht_produktgruppe.php
57. Webster J.,Ejiofor J Nanometer sized bumps improve prosthetic implant. Available
from URL: http://www.foresight .org/ conference/MNT 10 /abstracts / sinha /
index. Html Nanomedicine. Google search. Website : http://www.nano
biology.net/?gclid=Ckil_crqs40CFRAodYHzJug
58. Infonia. Equilase 10 with nanotechnologies. Available from URL:
http://www.infonia.co.kr/products/equilase.html
59. Slavkin H.C. Entering the era of molecular dentistry. JADA 1999 Mar; 130:413-417.

102
60. De Bruijn JD, Yuan H, Dekker R, Layrolle P, de Groot K, vanBlitterswijk CA.
Osteoinductive biomimetic calciumphosphate coatings and their potential use as a tissue-
engineering scaffold. In: Davies JE,editor. Bone engineering. Toronto: em squared Inc.;
2000.p. 421-31.
61. Journal of Oral and Maxillofacial Pathology: Vol. 18 Special Issue November 2014.
62. Sonia B Bhardwaj, Manjula Mehta, K Gauba: Nanotechnology: Role in dental biofilms:
Indian J Dent Res, 20(4), 2009.
63. Sara Tavassoli-Hojjati Mohammad Mahdavi Faezeh Hamzeh Mohammad Bagher
Rezvani fatemeh Ahmadian Babaki Hoorieh Saderi Mohammad Javad Kharazifard:
Effect of Nano Titanium Dioxide on Self-Cleaning and Antibacterial Properties of Dental
Mirrors: Journal Dental School 2013; 31(2):104-112.
64. Funakoshi K, Nonami T. Photocatalytic treatments on dental mirror surfaces using
hydrolysis of titanium alkoxide. J Coat Technol Res 2007; 4: 327-333.
65. J.K. Kim, R. Shukla, L. Casagrande, C. Sedgley, J.E. Nör, J.R. Baker, Jr., and E.E. Hill:
Differentiating Dental Pulp Cells via RGD-Dendrimer Conjugates: J Dent Res 89(12)
2010;1433-1437.
66. J.F. Zhang, R. Wu, Y. Fan, S. Liao1, Y. Wang, Z.T. Wen, and X. Xu : Antibacterial
Dental Composites with Chlorhexidine and Mesoporous Silica: J Dent Res 93(12):1283-
1289, 2014.
67. M. A. Saghiri, K. Asgar, M. Lotfi & F. Garcia-Godoy: Nanomodification of mineral
trioxide aggregate for enhanced physiochemical properties: International Endodontic
Journal, 45, 979–988, 2012.
68. Waqar Ahmed and St John Crean:Nanotechnology for Tooth Regeneration: FACULTY
DENTAL JOURNAL; January 2014;Volume 5;Issue 1.
69. M. Hannig , C. Hannig: Nanotechnology and its role in Caries Therapy: Adv Dent Res
24(2):53-57, 2012.
70. Former White House Science Advisor Warns that Nanotechnology's Potential Threatened
by Weak Public Education and Outreach available on website:
http://nanotechwire.com/news.asp?nid=4108
71. Hazards of nanotechnology available from website:
http://tqnyc.org/NYC040656/hazard.html

103
72. Nanomedicine: An unresolved regulatory issue. VS Chan
Innovative Therapeutics Group, Centre for Drug Administration, Health Sciences
Authority, Regul Toxicol Pharmacol (2006).
73. .Cruz L, Schaffazick SR, Dalla Costa T, Soares LU, Mezzalira G, da Silveira NP, Shapoval
ES, Pohlmann AR, Guterres SS. J. Nanosci. Nanotechnol. 2006a;6:3154–62.
74. Sanjeeb K Sahoo, Ph.D :Applications of Nanomedicine ; APBN ;Vol. 9 ;No. 20 ; 2005.
75. Zhermack Elite H-D+ Nano technology Silicones: Google search.
http://www.carisbg.com/?81&02&9674
76. Sivaramakrishnan SM, Neelakanthan P. Nanotechnology in dentistry- what does the
future hold in store? Dentistry 2014; 4: 1-3.

104