nanotechnology: a boon to dentistry

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78 JDSOR Nanotechnology: A Boon to Dentistry 1 Mayuresh J Baheti, 2 Nandlal Girijalal Toshniwal ABSTRACT Dentistry is frequently facing revolutions in order to provide a most reliable and comfortable therapeutic option for the patients. Recently, nanotechnology has emerged as a new science exploi- ting specific phenomena and direct manipulation of materials on nanoscale. Nanorobotics is the technology of creating machines or robots at or close to the microscopic scale of a nanometer (10 –9 m). Nanotechnology, being an interdisciplinary field, has three main extensively overlapping areas, nanoelectronics, nanomaterials, and nanobiotechnology, and these have ap- plications in healthcare. Nanotechnology has diverse applica- tions in the field of dendritic polymers, including sophisticated visualization of dental structures, improvement in the physical properties of materials, mimicking the natural processes in tooth development, and in the use of specialized nanomachines called nanorobots to execute regular dental measures. Different pos- sible approaches of nanotechnology in dentistry might include the application of nanotechnology to local anesthesia, dentition renaturalization, the permanent cure for hypersensitivity, com- plete orthodontic realignment in a single visit, and continuous oral health maintenance using mechanical dentifrobots. The present article aims to provide an early glimpse on the impact and future implication of nanorobotics and highlights the role of nanomaterials and their potential to be used in the diagnosis and management of oral diseases in dentistry. Keywords: Nanodentistry, Nanorobots, Nanotechnology, Nanostructure. How to cite this article: Baheti MJ, Toshniwal NG. Nano- technology: A Boon to Dentistry. J Dent Sci Oral Rehab 2014; 5(2):78-88. Source of support: Nil Conflict of interest: None INTRODUCTION Science is undergoing yet another change in helping mankind enter a new era, the era of nanotechnology. Nanotechnology era is fast approaching which was unheard of two decades ago. The opportunity to witness the beginning of a pionee- ring development in technology is encountered rarely. All disciplines of human life will be impacted by advances in REVIEW ARTICLE 1 Postgraduate Student, 2 Professor and Head 1,2 Department of Orthodontics and Dentofacial Orthopedics Rural Dental College, Pravara Institute of Medical Sciences Loni, Maharashtra, India Corresponding Author: Mayuresh J Baheti, Postgraduate Stu- dent, Department of Orthodontics and Dentofacial Orthopedics Rural Dental College, Pravara Institute of Medical Sciences Loni-413736, Maharashtra, India, Phone: +91-9028822692 e-mail: [email protected] 10.5005/jp-journals-10039-1018 nanotechnology in the near future. The growing interest in this field is giving emergence to new field called ‘nano- medicine’, a science and technology of diagnosing, treating and preventing diseases, and preserving and improving human health, using nanoscale structured materials. Once one considers other potential applications of nanotechnology to medicine, it is not difficult to imagine what nanodentistry would look like. The present article aims to provide an early glimpse on the impact and future implication of nanorobotics and highlights the role of nanomaterials and their potential to be used in the diagnosis and management of oral diseases in dentistry. THINKING EARLY BY A PHYSICIST Physicist Richard P Feynman, in 1960, had the first notion of how nanotechnology could be applied to medicine. In his historic lecture in 1959, he concluded saying, ‘This is a development which, I think, cannot be avoided.’ 1 HISTORY The term ‘nanotechnology’ was first used by Norio Taniguchi in 1974, though it was not widely known. Inspired by Feynman’s concepts, K Eric Drexler independently used the term ‘nanotechnology’ in 1986. Humans have been using nanotechnology for a long time without realizing it. The processes of making steel, vulcanizing rubber and sharpening a dental instrument, all rely on manipulations of nanoparticles. Richard Zsigmondy studied nanomaterials in the early 20th century, and later discoveries culminated in ideas presented by Nobel Prize winning physicist, Richard Feynman in a lecture called ‘Plenty of Room at the Bottom’ in 1959, in which he explored the implications of matter manipulation. 1 Applications began in the 1980s with the invention of the scanning tunneling microscope and the discovery of carbon nanotubes and fullerenes. 2 Nanotechnology—The Real Meaning ‘Nano’ is derived from the Greek word ‘vaos’, meaning ‘dwarf’; it is usually combined with a noun to form words, such as nanometer, nanotechnology, or nanorobot. Nanotech- nology is a promising area that deals with nanometer (10 –9 m) sized items. Nanotechnology is the science of manipulating matter measured in the billionths of meters or nanometer, roughly the size of 2 or 3 atoms. 3

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Page 1: Nanotechnology: A Boon to Dentistry

Mayuresh J Baheti, Nandlal Girijalal Toshniwal

78

JDSOR

Nanotechnology: A Boon to Dentistry1Mayuresh J Baheti, 2Nandlal Girijalal Toshniwal

ABSTRACTDentistry is frequently facing revolutions in order to provide a most reliable and comfortable therapeutic option for the patients. Recently, nanotechnology has emerged as a new science exploi­ting specific phenomena and direct manipulation of materials on nanoscale. Nanorobotics is the technology of creating machines or robots at or close to the microscopic scale of a nanometer (10–9 m). Nanotechnology, being an inter disciplinary field, has three main extensively overlapping areas, nanoelectronics, nanomaterials, and nanobiotechnology, and these have ap­plications in healthcare. Nanotechnology has diverse applica­tions in the field of dendritic polymers, including sophisticated visualization of dental structures, improvement in the physical properties of materials, mimicking the natural processes in tooth development, and in the use of specialized nanomachines called nanorobots to execute regular dental measures. Different pos­sible approaches of nanotechnology in dentistry might include the application of nanotechnology to local anesthesia, dentition renaturalization, the permanent cure for hypersensitivity, com­plete orthodontic realignment in a single visit, and continuous oral health maintenance using mechanical dentifrobots. The present article aims to provide an early glimpse on the impact and future implication of nanorobotics and highlights the role of nanomaterials and their potential to be used in the diagnosis and management of oral diseases in dentistry.

Keywords: Nanodentistry, Nanorobots, Nanotechnology, Nanostructure.

How to cite this article: Baheti MJ, Toshniwal NG. Nano­technology: A Boon to Dentistry. J Dent Sci Oral Rehab 2014; 5(2):78­88.

Source of support: Nil

Conflict of interest: None

INTRODUCTION

Science is undergoing yet another change in helping mankind enter a new era, the era of nanotechnology. Nanotechnology era is fast approaching which was unheard of two decades ago. The opportunity to witness the beginning of a pionee­ring development in technology is encountered rarely. All disciplines of human life will be impacted by advances in

REVIEW ARTICLE

1Postgraduate Student, 2Professor and Head1,2Department of Orthodontics and Dentofacial Orthopedics Rural Dental College, Pravara Institute of Medical Sciences Loni, Maharashtra, India

Corresponding Author: Mayuresh J Baheti, Postgraduate Stu­dent, Department of Orthodontics and Dentofacial Orthopedics Rural Dental College, Pravara Institute of Medical Sciences Loni­413736, Maharashtra, India, Phone: +91­9028822692 e­mail: [email protected]

10.5005/jp-journals-10039-1018

nanotechnology in the near future. The growing interest in this field is giving emergence to new field called ‘nano­medicine’, a science and technology of diagnosing, treating and preventing diseases, and preserving and improving human health, using nanoscale structured materials. Once one considers other potential applications of nanotechnology to medicine, it is not difficult to imagine what nanodentistry would look like. The present article aims to provide an early glimpse on the impact and future implication of nanorobotics and highlights the role of nanomaterials and their potential to be used in the diagnosis and management of oral diseases in dentistry.

THINKING EARLY BY A PHYSICIST

Physicist Richard P Feynman, in 1960, had the first notion of how nanotechnology could be applied to medicine. In his historic lecture in 1959, he concluded saying, ‘This is a development which, I think, cannot be avoided.’1

HISTORY

The term ‘nanotechnology’ was first used by Norio Taniguchi in 1974, though it was not widely known. Inspired by Feynman’s concepts, K Eric Drexler independently used the term ‘nanotechnology’ in 1986. Humans have been using nanotechnology for a long time without reali zing it. The processes of making steel, vulcanizing rubber and sharpening a dental instrument, all rely on manipulations of nanoparticles. Richard Zsigmondy studied nanomaterials in the early 20th century, and later discoveries culminated in ideas presented by Nobel Prize winning physicist, Richard Feynman in a lecture called ‘Plenty of Room at the Bottom’ in 1959, in which he explored the implications of matter manipulation.1 Applications began in the 1980s with the invention of the scanning tunneling microscope and the discovery of carbon nanotubes and fullerenes.2

Nanotechnology—The Real Meaning

‘Nano’ is derived from the Greek word ‘vaos’, meaning ‘dwarf’; it is usually combined with a noun to form words, such as nanometer, nanotechnology, or nanorobot. Nanotech­nology is a promising area that deals with nanometer (10–9 m) sized items. Nanotechnology is the science of mani pulating matter measured in the billionths of meters or nanometer, roughly the size of 2 or 3 atoms.3

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In the literature, both a fairly broad as well as a rather narrow concept of nanotechnology is employed. The first sig nifies any technology smaller than microtechnology. In contrast, the latter stands for the technology to program and manipulate matter with molecular precision and to scale it to 3D products of arbitrary size.

Nanorobots: What are They?

Nanorobots are theoretical microscopic devices measured on the scale of nanometers (1 nm equals one millionth of 1 mm). When fully realized from the hypothetical stage, they would work at the atomic, molecular and cellular levels to perform tasks in both the medical and industrial fields that have heretofore been the stuff of science fiction (Fig. 1). Nanomedicine’s nanorobots are so tiny that they can easily traverse the human body. Scientists report the exterior of a nanorobot will likely be constructed of carbon atoms in a diamondoid structure because of its inert properties and strength. Super smooth surfaces will lessen the likelihood of triggering the body’s immune system, allowing the nano robots to go about their business unimpeded. Glucose or natural body sugars and oxygen might be a source for propulsion and the nanorobot will have other biochemical or molecular parts depending on its task.4

Nanomachines are largely in the research and development phase, but some primitive molecular machines have been tested. An example is a sensor having a switch approximately 1.5 nm across, capable of counting specific molecules in a chemical sample. Another potential application is the detection of toxic chemicals, and the measurement of their concentrations in the environment.5

What Made Nanotechnology Possible?

Two achievements developed nanotechnology through the scientific method rather than conceptual; first, the invention of scanning tunneling microscope (STM) by Binnig and

Rohrer in 1981, by which the individual atoms were easily identified for the first time. Some of the limitations of this microscope were eliminated through the invention of the atomic force microscope, which could image nonconducting materials such as organic molecules. This invention was integral for the study of carbon buckyballs, discovered at Rice University in 1985-1986 and carbon nanotubes few years later.6 Man’s desire to create materials with better improved properties is ever lasting and still pursuing. Nanotechnology has an immense potential in fulfilling this desire; the properties of materials change drastically by just manipulating the way atoms or molecules are arranged.6

Elements and Mechanism of Action on Nanorobots

Nanorobots in medicine are used for the purpose of main­taining and protecting the human body against patho gens. They are 0.5 to 3 m in diameter and are cons tructed of parts with dimensions in the range of 1 to 100 nm. The main element used is carbon in the form of diamond/fullerene nano composite due to its increased strength and chemical inert ness. Other light elements such as oxygen, nitrogen can be used for special purposes. The external passive diamond coating provides a smooth, flawless coating and evokes less reaction from the body’s immune system.6

The powering of nanorobots can be done by metabolizing local glucose, oxygen and externally supplied acoustic energy. They can be controlled by onboard computers capable of performing around 1000 or more computations per second. Communication with the device can be achieved by broadcast type acoustic signaling. A navigational network installed in the body provides high positional accuracy to all passing nanorobots and keep track of the various devices in the body. Nanorobots are able to distinguish between different cell types by checking their surface antigens. Building nanorobots involves sensors, actuators, control, power, communications and interfacial signals across spatial scales and between organic/inorganic as well as biotic/abiotic systems. Nanoactuators can be controlled by light or electrical signals.7 When the task of the nanorobots is com pleted, they can be retrieved by allowing them to effuse themselves via the usual human excretory channels. They can also be removed by active scavenger systems.7

TECHNIQUES OF NANOTECHNOLOGY8

Top-down Technique

These seek to create smaller devices by using larger ones to direct their assembly. Here, small features are made by starting with larger materials patterning and carving down to make nanoscale structures in precise patterns. Complex Fig. 1: Dental nanorobots

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structures containing hundreds of millions of precisely positioned nanostructures can be fabricated. Materials redu­ced to the nanoscale can suddenly show very different pro­perties, enabling unique applications. As the size of system decreases, there is an increase in the ratio of surface area to volume and number of physical phenomena becomes noti ce ably pronounced which include statistical as well as quan tum mechanical effects.

Bottom-up Technique

These seek to arrange smaller components into more complex assembly. This begins by designing and synthesizing custom­ made molecules that have the ability to self­assemble or self­organize into higher order mesoscale or macroscale structures. Modern synthetic chemistry has reached the point where it is possible to prepare small molecules to almost any structure. These methods are used today to manufacture a wide variety of useful chemicals such as pharmaceuticals or commercial polymers. Such bottom­up approaches are much cheaper than top­down methods, but could potentially be overwhelmed as the size and complexity of the desired assembly increases.

Nanomaterials

Siegel has classified nanomaterials as zero-dimensional, one­dimensional, two­dimensional and three­dimensional nanostructures.9 Various nanostructures include the following:• Nanoparticles• Nanopores• Nanotubes• Nanorods• Nanospheres• Nanofibers• Nanoshells• Dendrimers• Liposomes• Fullerenes• Nanowires• Nanobelts• Nanorings• Nanocapsules• Quantum dots• Dendrimers and dendritic copolymers.

Inorganic nanoparticles either currently in use or under development include:• Semiconductor nanoparticles• Metal nanoparticles• Metal oxide nanoparticles• Silica nanoparticles• Polyoxometalates• Gold nanocrystals.

Nanomedicine and Nanodentistry

Nanomedicine is the science and technology of diagnosing, treating and preventing disease and traumatic injury relieving pain and preserving and improving human health through the use of nanoscale structured materials, biotechnology and genetic engineering, eventually complex molecular machine systems and nanorobots.10,11

Nanodentistry will make possible the maintenance of near­perfect oral health through the use of nanomaterials, biotechnology including tissue engineering and nanorobotics.

Nanodentistry

Nanodentistry includes:• Nanorobotics• Nanodiagnostics• Nanomaterials.

NANOROBOTICS

Local Anesthesia

Micron­sized active analgesic dental robots suspended in a colloidal solution instilled on the patient’s gingiva reach the pulp via the gingival sulcus, lamina propria and dentinal tubules. This is guided by a combination of che mical gra­dients, temperature differentials and even positional naviga­tion which are all under the control of onboard nano computer as directed by the dentist. Assuming a total path length of about 10 mm from the tooth surface to the pulp and a modest travel speed of 100 µm/s, nanorobots can complete the journey into the pulp chamber in approximately 100 seconds.

Once installed in the pulp and having established control over nerve-impulse traffic, the analgesic dental nanorobots maybe commanded by the dentist to shut down all sensitivity in any tooth that requires treatment. When the dentist presses the icon for the desired tooth on the hand­held controller display, the selected tooth immediately numbs. After the oral procedures are completed, the dentist orders the nanorobots (via the same acoustic data links) to restore all sensation, to relinquish control of nerve traffic and to egress from the tooth via similar pathways used for ingress; following this, they are aspirated. Nanorobotic analgesics offer greater patient comfort and reduced anxiety without the use of needles, greater selectivity and controllability of the analgesic effect, fast and completely reversible action, and avoidance of most side effects and complications12 (Fig. 2).

Dental Hypersensitivity

Natural hypersensitive teeth have eight times higher surface density of dentinal tubules and diameter with twice as large as nonsensitive teeth. Reconstructive dental nanorobots,

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using native biological materials, could selectively and precisely occlude specific tubules within minutes, offering patients a quick and permanent cure.10,12,13

On reaching the dentin, the nanorobots enter dentinal tubular holes that are 1 to 4 μm in diameter and pro ceed toward the pulp, guided by a combination of chemical gra­dients, temperature differentials and even position of navi­gation, all under the control of the onboard nanocomputer as directed by the dentist. There are many pathways to travel nanorobots from dentin to pulp. Because of different tubular branching patterns, tubular density may present significant challenge to navigation. Assuming a total path of length of about 10 mm from the tooth surface to the pulp and a modest travel speed of about 100 μm/second, nanorobots can complete the journey into the pulp chamber in approximately 100 seconds. The presence of natural cells that are constantly in motion around and inside the teeth, including human gingival, pulpal fibroblasts, cementoblasts, odontoblasts, and bacteria inside dentinal tubules, lymphocytes within the pulp or lamina propria suggests that such journey be feasible by cell­sized nanorobots of similar mobility.10,13

Dental Biomimetics

The most interesting venue for speculation on the nano­restoration of tooth structure is that of nanotechno logy mimi cking processes that occur in nature (biomimetics), such as the formation of dental enamel. Through an affor­dable desktop manufacturing facility, fabrication of a new tooth in the dentist’s office within the time and economic constraints of a typical dental office visit, complete dentition replacement therapy will become feasible soon.

Chen et al utilizing nanotechnology simulated the natural biomineralization process to create the dental enamel, using highly organized microarchitectural units of nanorod­like calcium hydroxyapatite crystals arranged roughly parallel to each other.14

Dental 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 of natural enamel, or contemporary ceramic veneers as well as good biocompa­tibility. Pure sapphire and diamond are brittle and prone to fracture resistant as part of a nanostructure composite mate­rial that possibly includes embedded carbon nanotubes.14

Orthodontic Treatment

Sliding a tooth along an archwire involves a frictional type of force that resists this movement. Use of excessive ortho dontic force might cause loss of anchorage and root resorption. In a study published by Katz, a reduction in fric­tion has been reported by coating the orthodontic wire with inorganic fullerene-like tungsten disulfide nanoparticles (IF-WS2), which are known for their excellent dry lubri cation properties.15 In future, orthodontic nanorobots could directly manipulate the periodontal tissues, including gin givae, perio­dontal ligament, cementum and alveolar bone, allowing rapid and painless tooth straightening, rotating and vertical repositioning within minutes to hours. This is in contrast to current molar­uprighting techniques, which require weeks or months to complete (Fig. 3).

Nanorobotic Dentifrice (Dentifrobots)

A mouthwash full of smart nanorobots could identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystem.16 Further the devices would identify particles of food, plaque or tartar and lift them from the teeth to be rinsed away. Being suspended in liquid and able to swim about, devices would be able to reach surfaces beyond reach of toothbrush bristles or the fibers of floss. 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.

These invisibly small dentifrobots (1­10 microns), crawl­ing at 1 to 10 microns/sec, would be inexpensive, purely mecha nical devices, that would safely deactivate themselves if swallowed, and would be programmed with strict occlusal avoidance protocol. Properly configured dentifrobots could

Fig. 2: Nanorobots in local anesthetic solution

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identify and destroy pathogenic bacteria residing in the plaque and elsewhere, while allowing the ~500 species of harmless oral microflora to flourish in a healthy ecosystem. Dentifrobots also would provide a continuous barrier to halitosis, since bacterial putrefication is the central metabolic process involved in oral malodor.10,17 With this kind of daily dental care available from an early age, conventional tooth decay and gingival disease will disappear.

Renaturalization Procedures

Dentition renaturalization procedures may become a popular addition to the future dental practice, made possible through esthetic dentistry. This can be mainly used in patients who desire to have their old dental amalgams excavated and their teeth remanufactured with native biological mate­rials. Full coronal renaturalization procedures, in which all fillings and crowns are removed, and the affected teeth are remanufactured to become indistinguishable from the original teeth.10 However, demand will grow for full coronal renaturalization procedures, in which all fillings, crowns and other 20th century modifications to the visible dentition are removed, with the affected teeth remanufactured to become indistinguishable from the original teeth.

Nanovectors

A calcium phosphate nanoparticle was found to potentially serve as a good vehicle (nanovectors) to deliver target genes to fibroblasts for periodontal regenerative purposes in vitro.18

Surgical Nanorobotics

A surgical nanorobot, programmed or guided by a dentist, could act as a semiautonomous onsite surgeon inside the human body. Such a device could perform various functions such as searching for pathology and then diagnosing and correcting lesions by nanomanipulation, coordinated by an onboard computer while maintaining contact with the supervising surgeon via the coded ultrasound signals.19

NANODIAGNOSTICS (DIAGNOSIS OF ORAL CANCER AND OTHER DISEASES)

Nanoscale Cantilevers

Nanoscale cantilevers are flexible beams resembling a row of diving boards. They are built using semiconductor lithographic techniques that can be engineered to bind to molecules associated with cancer. They may bind to altered DNA sequences or proteins that are present in certain types of cancer and can provide rapid and sensitive detection of cancer­related molecules.20 As a cancer cell secretes its mole cular products (DNA sequences or proteins), the anti­bodies coated on the cantilever fingers selectively bind to these secreted proteins, changing the physical properties of the cantilever and signaling the presence of cancer.

Nanopores

A nanopore is simply a small hole, of the order of 1 nm in internal diameter. Nanopore sequencing is one of the most promising technologies being developed as a cheap and fast alternative to the conventional Sanger sequencing method. Protein or synthetic nanopores have been used to detect DNA or RNA molecules. Because DNA passes through a nanopore, scientists can observe the shape and electrical properties of each base, or letter, on the strand that can be effective in oral cancer detection and treatment.21

Nanotubes

Nanotubes of various types have been investigated for dental applications. They are carbon rods about half the diameter of a molecule of DNA that not only can detect the pre sence of altered genes but also may help researchers pinpoint the exact location of those changes. A multidisciplinary team at the Massachusetts Institute of Technology (MIT) has develo ped carbon nanotubes that can be used as sensors for cancer drugs and other DNA damaging agents inside living cells. Carbon nanotubes fluoresce near infrared light takes advantage whereas human tissue does not. The interaction between DNA and the DNA disruptor changes the intensity or wavelength of the fluorescent light emitted by nanotubes.22 Titanium oxide nanotubes have been shown

Fig. 3: Orthodontic nanorobots

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in vitro to accelerate the kinetics of HA formation, mainly in context of bone­growth applications for dental implant coatings. More recently, modified single-walled carbon nanotubes (SWCNT) have been shown to improve the flexural strength of RBC. These SWCNT had silicon dioxide applied to them in conjunction with specialized organo-silane­bonding agents.23

Quantum Dots

These are tiny crystals that glow when they are stimulated by ultraviolet light. When injected into the body, they would drift around until encountering cancerous tissue. The deadly cells would latch onto a special coating on the glowing dots. The light particles would serve as a beacon to show doctors where the disease has spread. Quantum dots bind themselves to proteins unique to cancer cells, literally bringing tumors to light. Quantum dots can be used as photo-sensitizers which can mediate targeted cellular destruction. They can bind to antibody present on surface of target cell and when stimulated by UV light, will release reactive oxygen species and this will be lethal to target cell. This therapy can be used to fight with malignant cells.24

Nanoelectromechanical Systems (NEMs)

Nanotechnology­based NEMS biosensors that exhibit exquisite sensitivity and specificity for analyte detection, down to single molecule level are being developed. They convert (bio)chemical to electrical signal.25

Cantilever Array Sensors

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.

These are extremely useful in the diagnosis of oral cancer and diabetes mellitus and for the detection of bacteria, fungi and viruses.

Oral Fluid Nano Sensor Test (OFNASET)

Oral fluid nano sensor test (OFNASET) technology that combines self­assembled monolayers (SAM), bionano­technology, cyclic enzymatic amplification, and microfluidics for detection of salivary biomarkers for oral cancer. It was demonstrated that a combination of two salivary proteomic biomarkers (thioredoxin and IL-8) and four salivary mRNA biomarkers (SAT, ODZ, IL-8, and IL-1b) detected oral cancer with high specificity and sensitivity.26

Optical Nanobiosensor

The nanobiosensor is a unique fiberoptics-based tool which allows the minimally invasive analysis of intracellular compo nents such as cytochrome C, an important protein invol ved in the production of cellular energy as well as in apoptosis, or programmed cell death.26

Lab-on-a-Chip Method

Lab-on-a-chip (LOC) is a device which integrates several labo ratory functions on a single chip. LOCs deal with the hand ling of extremely small fluid volumes down to less than picoliters.

Assays are performed on chemically sensitized beads populated into etched silicon wafers with embedded fluid hand ling and optical detection capabilities. Com plex assays can be performed with small sample volu mes, short analysis times, and markedly reduced reagent costs. LOC methodologies have been used to assess the levels of interleukin-1beta (IL-1beta), C-reactive protein (CRP), and matrix metalloproteinase-8 (MMP-8) in whole saliva, which are potential uses of these biomarkers for diagnosing and categorizing the severity and extent of periodontitis.27,28

NANOMATERIALS IN DENTISTRY

Nanocomposites

Nonagglomerated discrete nanoparticles are homogeneously distributed in resins or coatings to produce nanocomposites. The nanofiller used includes an aluminosilicate powder having a mean particle size of 80 mm and a 1:4 M ratio of alumina to silica and a refractive index of 1.508.17

Advantages

Superior hardness, flexible strength, modulus of elasticity, translucency, esthetic appeal, excellent color density, high polish and polish retention and excellent handling properties.

Nanofilled Resin-modified Glass Ionomer

A new nanofilled RMGI restorative material has been intro-duced for restoration of primary teeth and small cavities in permanent teeth. It is based on a prior RMGI with a simpli-fied dispensing and mixing system (paste/paste) that requires the use of a priming step, but no separate condi tioning step. Its primary curing mechanism is by light activation, and no redox or self­curing occurs during setting. Apart from the user-friendliness, the major innovation of this mate-rial invol ves the incorporation of nanotechnology, which allows a highly packed filler composition (69%), of which approximately two-thirds are nanofillers.

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Nanosolution

Nanosolutions produce unique and dispersible nanoparticles, which can be added to various solvents, paints and polymers in which they are dispersed homogenously. Nanotechnology in bonding agents ensures homogeneity and that the adhesive is perfectly mixed every time.29 Nanoparticles have also been used as sterilizing solutions in the form of nanosized emulsified oil droplets that bombard pathogens.

Nano-optimized Moldable Ceramics

• Nanofillers enhance polishing ability and reduce wear.• Nanopigments adjust the shade of the restoration to the

surrounding teeth (chameleon effect).• Nanomodifiers increase the stability of the material and

prevent sticking to instruments.30

Impression Material

Impression material is available with nanotechnology appli­cation. Nanofillers are integrated in vinylpolysiloxanes, pro ducing a unique addition of siloxane impression mate­rial. The material has better flow, improved hydrophilic properties and enhanced detail precision.31

Nanoencapsulation

South West Research Institute (SWRI) has developed targe­ted release systems that encompass nanocapsules including novel vaccines, antibiotics and drug delivery with reduced side effects. Future specialized nanoparticles could be engineered to target oral tissues, including cells derived from the periodontium.17 At present, targeted delivery of genes and drugs to human liver has been developed by Osaka University in Japan 2003. Engineered Hepatitis B virus enveloped L particles were allowed to form hollow nanoparticles displaying a peptide that is indispensible 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.

Other Products manufactured by SWRI

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

b. Medical appendages for instantaneous healing: • Biodegradable nanofibers—delivery platform for

hemostatic. • Wound dressings with silk nanofibers in development. • Nanocrystalline silver particles with antimicrobial

properties on wound dressings (ActicoatTM, UK).17

Silver is an antiseptic, targeting a broad spectrum of Gram positive and Gram negative bacteria such as MRSE, MRSA and even vancomycin­resistant strains. Pure silver

particles at nanoscale have greater surface­to­mass ratio offering greater solubility and chemical reactivity, and higher antibacterial activity compared to conventional silver preparations.32

c. Bone targeting nanocarriers.33

Calcium phosphate-based biomaterial is an easily flow-able, moldable paste that conforms to and interdigitates with host bone supporting growth of cartilage and bone cells.

Materials to induce Bone Growth

Bone is a natural nanostructured composite composed of organic compounds (mainly collagen) reinforced with inorganic ions (HA). It is this natural nanostructure that nano technology aims to emulate for dental applications. Nano bone uses the principle of smaller the particle size, larger the surface area in volume. The nanocrystallites show a loose microstructure, with nanopores situated between the crys tallites. This material structure will be com pleted by pores in the micrometer area. By following this process, a rough surface area is formed on the boundary layer between the biomaterial and cell, which is very important for fast cell growth. All pores are interconnecting. Because the cells are too big for the small pores, blood plasma containing all the important proteins is retained in the interstices.33

Hydroxyapatite nanoparticles used to treat bone defects are as follows:• Ostium (Osartis GmbH, Germany) HA• VITOSSO (Orthovita, Inc, USA) HA + TCP• NanOSSTM (Angstrom Medica, USA) HA.

Recently developed nanobioactive glass in concentration less than 4 mg/ml was found to be biocompatible with gingival fibroblasts in an in vitro study.34 Calcium sulfate is used to fill small voids such as those found in postextraction sockets and periodontal bone defects and as an adjunct to the longer lasting bone grafting materials. Dr Ricci has formulated a new calcium sulfate­based nanocomposite. BoneGen-TR resorbs more slowly and regenerates bone more consistently.

Nanoneedles

Scientists have achieved a subtle surgical operation on a parti cular living cell, by means of a needle that is just a few billionths of a meter wide. Nanoneedles are nanosized stain less steel needles, which will make cell surgery possi­ble in the near future. Nanoneedles can be used to deliver mole cules, such as nucleic acids, proteins, or other chemi­cals to the nucleus, or may even be used to carry out cell surgery.35 Using the nanoneedle approach, we can get to a very specific location within the nucleus; this is the key advantage of this method.

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Trade name: Sandvik Bioline, RK 91TM needles (AB Sandvik, Sweden).

Nanotweezers

The Danish research group (Nanohand) has developed nano­tweezers, which can be used for both imaging and manipu­lation of nanosized objects to make cell surgery feasible in the near future. The dental research in the area of single particle surveillance and manipulation, based on laser nanotweezer technology. In the continuation of research into manipulating carbon nanotubes inside scanning electron microscopes, 21st century nanosmiths have begun crafting a suite of research tools, including nanotweezers, nanobearings and nano­oscillators. These nanotweezer probes consist of two wires tapered consecutively through a nanopipette and kept electrically isolated.36

Self-assembly

It is an autonomous organization of components into pat­terns or structures without human intervention. Polyelectro­lyte materials bearing a number of charged groups are most commonly used in self­assembly as they enable stable, smooth, homogeneous films to be formed with a num ber of functional groups. Of these, the best studied systems are poly­allylamine/polystyrene sulfonate and diazoresin/polystyrene sulfonate.11,37

Recently, the use of pH-induced self-assembly of a peptide-amphiphile is used to artificially construct a nano­structured fibrous scaffold with the structural features of extracellular matrix. Furthermore, after cross­linking, the newly produced fibers are able to direct mineralization of hydroxyapatite to form a composite material in which the crystallographic axes of hydroxyapatite are aligned with the long axes of the fibers which mimic the periodontium.

Nanomaterials for Periodontal Drug Delivery

Nanomaterials widely explored for controlled drug release are hollow spheres, core­shell structure, nanotubes and nano composite. Drugs can be incorporated into nano spheres composed of a biodegradable polymer, and this allows for timed release of the drug as the nanospheres degrade facili­tating site-specific drug delivery (Fig. 4).

Recently triclosan­loaded nanoparticles prepared using poly (d, l­lactide­coglycolide), poly (d,l­lactide) and cellulose acetate phthalate was found to be effective in achieving reduction of inflammation.38,39 Tetracycline incorporated into microspheres is available as Arestin for drug delivery by local means into periodontal pocket. A nanostructured 8.5% doxycycline gel was observed to afford periodontal surface preservation following experimental periodontal disease in rats.40

Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) is a new treat­ment method for the removal of infectious pathogens using a photosensitizer and light of a specific wavelength, e.g. toluidine blue with a wavelength of about 600 nm. Recently, Methylene blue (photosensitizer) has been encapsulated within poly (D,L lactidecoglycolide) (PLGA) nanoparticles (≈ 150-200 nm in diameter) and was found to offer a novel design of nanoplatform for enhanced drug delivery and photo destruction of oral biofilms. A new photosensitizer, indo cyanine green (ICG)-loaded nanospheres with an 805 nm wavelength low­level diode laser irradiation showed an aPDT­like effect, which might be useful for a potential photo dynamic periodontal therapy.41

Implants

Nanotechnologies are increasingly used for surface modi­fi cations of dental implants as surfaces. Properties, such as chemistry and roughness play a determinant role in achieving and maintaining their long­term stability in bone tissue. Direct bone­to­implant contact is desired for a biomechanical anchoring of implants to bone rather than fibrous tissue encap sulation.42

Recently, three nanostructured implant coatings are developed as follows:• Nanostructured diamond: They have ultra high hardness,

improved toughness over conventional microcrystalline dia­mond, low friction, and good adhesion to titanium alloys.43

• Nanostructured processing applied to hydroxyapatite coatings: This is used to achieve the desired mechanical characteristics and enhanced surface reactivity and has been found to increase osteoblast adhesion, proliferation, and mineralization.43

• Nanostructured metalloceramic coatings: These provide continuous variation from a nanocrystalline metallic bond at the interface to the hard ceramic bond on the surface.43

Fig. 4: Nanorobot drug delivery

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Nanostructured ceramics, carbon fibers, polymers, metals and composites enhance osteoblast adhesion and calcium/phosphate mineral deposition. Studies have suggested that nanophase ZnO and TiO2 may reduce S. epidermidis adhesion and increase osteoblast functions necessary to promote the efficacy of orthopedic implants.44

Nanomaterials for Healing of Wounds

Nucryst (Wakefield, USA) has made a wound­healing material (dressing) that is generally used in specialist burn­treatment hospitals in America. The dressing contains nano­crystalline silver that stops 150 types of fungus and bacteria, including several bacteria that are resistant to anti biotics. Meanwhile, another company has placed nanoparticles into a plastic material to make it biocidal. This can be useful for devices that are placed inside the body.45

Bionic Mandible

The bionic mandible is helpful to reconstruct the entire man­di ble similar to normal mandible in function and sensa tion. It is not far from achieving, just like the first bionic arm cons tructed on Sullivan by Todd Kuiken and his team using nanotech­enabled robotic myoelectric prosthetic limb.46

Safety Aspects of Nanotechnology

Despite the numerous health and healthcare advances provided by nanomaterials and nanotechnologies, several side effects have also been noted. The main health risks related to the use of such devices consist of cytotoxicity, translocation to undesired cells, acute and chronic toxicity, unpredictable and indeterminate safety concerns, and the environmental impact of nanomaterials and nonbiocompa­tibility. Some nanoparticles show increased toxicity due to their increased surface area.47 Studies have shown carbon nanotubes to be cytotoxic and to induce granulomas in the lungs of laboratory animals. Also, metals and metallic oxide nanoparticles such as copper, cobalt, titanium oxide, and silicon oxide have inflammatory and toxic effects on cells. There is an ongoing debate among researchers about the bene fits and risks of nanotechnology. There are no exact Food and Drug Administration (FDA) regulations for the control of nanotechnology­based materials and allied problems. Overall, there is a critical requirement to standardize these nanotechnology­based products and delivery devices. Char­acterization, safety and environmental impact are the three main elements that need to be regulated. However, regulatory agencies like the FDA, the Environment Protection Agency (EPA) and the Nuclear Protection Agency are regulating the major health risks associated with nanomaterials. Workers may be exposed to nanosized particles in the manufacturing

or industrial use of nanomaterials; the National Institute for Occupational Safety and Health is performing research on nanoparticle interaction with body systems.47

In vivo­used nonpyrogenic nanorobot materials include bulk teflon, carbon powder, and monocrystal sapphire. How­ever, pyrogenic nanorobots include alumina, silica, and trace elements such as copper and zinc. Moreover, the pyrogenic path of the intrinsic nanodevice surface is circumvented by in vivo medical nanorobots. Nanorobots may liberate inhibitors, antagonists to the pyrogenic pathway, in a targeted manner to selectively take up the endogenous pyrogens, chemically alter them, and then release them back into the body in a harmless inactivated form. The benefits of nano­technology are enormous, therefore studies that examine the health, environmental, ethical and safety issues should improve our understanding of how to exploit the benefits and diminish the risks.

Role of a Dentist in Practicing Nanodentistry

The question arising in the mind is that if everything is done by computers, then what will be the role of a dentist? But thankfully the role of a dentist will evolve with time and it would be more exacting. Cases of simple neglect will become fewer and patients of rare disease and esthetic concern will become more. Treatment option will be more exac ting and we will be able to make the diagnosis with patient preference and his genetic make­up in mind. All this will demand, even more so than today, the best technical abilities, professional judgment, and strong doctor-patient interpersonal skills, that is the hallmark of the contemporary dentist.

The Future

Predicting the future is a risky business. However, it is not too early to consider, evaluate and attempt to shape potential effects of nanodentistry.14 Nanotechnology will change dentistry, healthcare and human life more profoundly than many developments of the past.45

Nanodentistry will lead to efficient and highly effective personalized dental treatments. A new generation of cell­based therapies will be available for regenerating tissues, and anti-inflammatory drugs and pain medications will be tailored to maximize efficacy and safety.22

The miracles of nanodentistry envisioned by dentists might sound unlikely, implausible or even heretic.31 Yet, the theoretical and applied research to turn them into reality is progressing rapidly. However, as with all technologies, nanotechnology carries a significant potential for misuse and abuse on a scale and scope never seen before. Nanodevices cannot be seen, yet carry powerful capabilities. They also

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Journal of Dental Sciences and Oral Rehabilitation, April-June 2014;5(2):78-88 87

JDSOR

have the potential to bring about significant benefits, such as improved health, better use of natural resources and reduced environmental pollution. The future might truly bring the days of miracle and wonder.

CONCLUSION

New science and technologies are previously making their way into all aspects of dental practice and have changed traditional approaches to diagnostics, risk assessment, pre­vention, and many other procedures. The impact of nano­technology on the field of dentistry is creating major changes with respect to improvement of health, diagnosis, and proper use of natural resources. Nanotechnology has had its greatest effect on restorative dentistry by contributing to the enhance­ment of previously established clinical RBC systems with the help of nanostructures, such as nanoparticles, nanotubes, nanorods, quantum dots, dendrimers, nanospheres, nano­fibers, etc. Moreover, nanocomposites or nanomaterials are likely to have a greater role in material development for the dental trade. Nanotechnology improves the understanding of the pathophysiologic basis of disease, conveys extra refinements in diagnosis, and yields more efficient treatment and preventive properties. Nanodentistry has the potential to preserve complete oral health with the use of nanomate­rials, biotechnology (including tissue engineering and gene therapy), and dental nanorobotics. In the future, it is expected that nanotechnology will develop into the core technology underlying dentistry. As with all emerging technologies, a successful future for nanotechnology will only be achieved through open sharing of ideas and research finding, through testing and frank discussion.

In short, ‘Future is coming, it will be amazing’. Time, advances, resources and needs will determine which pros­pects become reality. These and other exciting future appli­cations of manmade nanomachines will be limited only by our imagination.

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