<<

View metadata, citation and similar papers at core.ac.uk brought to you by CORE

+ MODEL provided by Elsevier - Publisher Connector Journal of Dental Sciences (2013) xx,1e9

Available online at www.sciencedirect.com ScienceDirect

journal homepage: www.e-jds.com

ORIGINAL ARTICLE : An emerging area in the field of dentistry

Shweta Jain a, Ashutosh Pal Jain b, Sourabh Jain b, Om Narayan Gupta b, Ankur Vaidya b*

a Department of Pharmaceutics, Adina Institute of Pharmaceutical Sciences, Sagar 470002, Madhya Pradesh, India b Bhagyoday Tirth Pharmacy College, Sagar 470002, Madhya Pradesh, India

Received 28 May 2013; Final revision received 23 August 2013 Available online ---

KEYWORDS Abstract Background/purpose: Nanotechnology is the science of material manipulation at dentistry; the billionth of a meter or nanometer scale, roughly the size of two or three atoms. Nanotech- nanomaterials; nology, being an interdisciplinary field, has three main extensively overlapping areas, nanoe- ; lectronics, nanomaterials, and nanobiotechnology, and these have applications in healthcare. nanostructures; Materials and methods: Nanotechnology is an intensifying area that covers a vast and diverse nanotechnology area of medical and dental applications. 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 mea- sures. Nanomaterials including nanoparticles, nanospheres, nanorods, nanotubes, nanofibers, dendrimers, and other nanostructures are imperative materials in modern research having a variety of applications in medicine and drug research. Results: The unique size of nanomaterials makes them fascinating carriers for dental products. The present review describes the clinical effectiveness of nanotechnology in the field of dentistry. The article also discusses various nanocarriers used in the field of dentistry. Copyright ª 2013, Association for Dental Sciences of the Republic of China. Published by Else- vier Taiwan LLC. All rights reserved.

* Corresponding author. Bhagyoday Tirth Pharmacy College, Sagar 470002, Madhya Pradesh, India. E-mail address: [email protected] (A. Vaidya).

1991-7902/$36 Copyright ª 2013, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.jds.2013.08.004

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL 2 S. Jain et al

Introduction improved health, better use of natural resources, and minimized environmental pollution. “Nano” is derived from the Greek word ao2, meaning The first nanosize device was contemplated by the late “dwarf”; it is usually combined with a noun to form words Nobel Prize-winning physicist Richard P. Feynman in 1959 such as nanometer, nanotechnology, or nanorobot. Nano- (he won the Nobel Prize for physics in 1965). In his technology is a promising area that deals with nanometer momentous lecture in 1959, he concluded by saying (10À9 m)-sized items. It was expected that nanotechnology “nanotechnology is a development which I think cannot be 4 will develop at some level for materials, devices, and sys- avoided”. In 2000, Freitas repeated the Richard Feynman tems. Previously, nanoparticles were studied because of prediction, which accompanied the origin of nano- their size-dependent physical and chemical properties.1 technology’s definition and vision that the atomic-level Today, they are at the commercial investigation phase.2 accuracy given by molecular devices operating at the 5 Dentistry, as an individual healthcare field, has not been nanoscale was a predictable technologic prospect. Nano- excused, having already been targeted directly with novel technology is the space at the nanoscale (i.e., one billionth ‘nanomaterials’; at the same time, it has indirectly gained of a meter), which is smaller than “micro” (one millionth of the benefit of nano-related progress in the electronics in- a meter) and larger than “pico” (one trillionth of a meter) dustry through the ongoing computerization of modern (Fig. 1). The rapidity of its appliance to dentistry has been practices. The speed at which progress has been made in less than innovative; nevertheless, the impact of nano- science has introduced nanotechnology to dentistry from its technology on dental education has grasped the attention theoretical basics instantly into the actual world. of dental professionals. Rising attention in upcoming medical applications of needs to conquer the confines of its nanotechnology in dentistry is foremost in the emergence application in order to improve the pathophysiologic basis of a novel field called nanomedicinedthe science and of disease, to bring more sophisticated diagnostic oppor- technology of diagnosing, treating, and preventing disease tunities, and to yield more effective therapies and pre- or injury, relieving pain, and of preserving and improving ventive properties. human health, using nanoscale-structured materials. Nanodentistry is a fascinating technique in the mainte- Outline of nanostructures used in dentistry nance of oral health with the use of nanomaterials, including tissue engineering and, ultimately, dental nano- Present day nanostructures exploit carefully structured robots. The expansion in new methods of expertise, largely nanocarriers such as nanoparticles, nanorods, nanospheres, those concerned with inspiring methods of study, has pre- nanotubes, nanofibers, dendrimers, quantum dots (QDs), viously altered the approach of sight and describes the nanopores, nanoscale cantilevers, nanoshells, and lipo- ideology of premium dental materials, tools, and practices. somes to target specific tissues and organs. These nano- However, at the same time, social issues involving public structures may serve in the diagnosis and cure of dental reception, ethics, regulation, and human safety must be disease, as well as providing anticancer agents in dentistry. addressed before molecular nanotechnology gains a firm position in the modern medical and dental armamentarium. Novel treatment prospects in dentistry include: local Nanoparticles anesthesia, dentition renaturalization, a permanent hy- persensitivity cure, complete orthodontic realignment A (Fig. 2A) is a particle that has one dimension during a single visit to the clinic, covalently-bonded dia- that is 100 nm or less in size. The properties of many con- mondized enamel, and continuous oral health maintenance ventional materials change when formed from nano- using mechanical dentifrobots. In this review, we focus on particles. Nanoparticles of different compositions the importance and applications of nanotechnology in the correspond to the most common use of nanoscale units in field of dentistry along with a brief introduction to the dentistry. They are presently being used in resin-based various nanostructures and nanomaterials that are been composite (RBC) restorations with published 2-year clin- 5 used in dental applications. ical results. Focus is being placed on the application of nanoparticles for dental composites and reformulations of interfacial silanes. These have been used for several years to coat and bond inorganic fillers into RBC matrices in Historical prospects of nanotechnology in dental restoratives along with tailoring of newer types of dentistry silane bonding agents for the use of nanoparticles in RBCs. Nanoparticles and related alterations of existing RBC sys- The term “nanotechnology” was proposed by Professor tems have established significant clinical usefulness.6 Kerie E. Drexler, a lecturer and researcher of nanotech- Nanohybrid RBCs are presently the most promising nology. In the last decade, several hypothetical predictions example of nanotechnology. Xia et al reported that surface have been made based on the prospective relevance for modification by the organosilane of TiO2 nanoparticles nanotechnology in dentistry, with varying levels of within a resin matrix was found to improve the micro- confidence.3 hardness and flexural strength of dental RBCs.7 Mayworm Nanotechnology changed dentistry and healthcare more et al discovered that the wear resistance of nanoparticles intensely than many developments of the past. Nanotech- containing dental composites increases after its storage in nology minimizes the misuse of dentistry that was seen artificial saliva.8 The storage of artificial saliva increases previously. It provides significant benefits, including the material’s wear resistance, signifying that material

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL Nanotechnology in the field of dentistry 3

Figure 1 The size of materials on nanoscale. bulking post-cure takes place and saliva absorption occurs nanoscale processes for inherent development in natural only on the surface of the composites. Vickers hardness and tooth. During the secretory stage of enamel, the Fourier transform infrared (FTIR) spectroscopy analyses amelogenin-rich organic matrix self-assembles to form before and after artificial saliva treatment further confirm nanosphere structures that are allied along the budding the effect. Surface microhardness of the composites de- enamel crystallites.12 Particularly, nanosphere assembly in creases after storage in artificial saliva whereas bulk combination with calcium phosphate deposition and ame- microhardness of the materials increases. Moreover, it has logenin nanochain assembly should be considered in a 13 been reported that radiopaque Ta2O5/SiO2 filler nano- restorative perspective. particles dispersed in a methacrylic matrix results in ad- hesives with radiopacity higher than dentin and enamel and Nanotubes excellent adhesive strength.9 Nanotubes (Fig. 2D) are nanometer-scale tube-like struc- Nanorods tures that have been explored for several dental applica- tions. Titanium oxide nanotubes have been revealed Nanorods (Fig. 2B) are nanoscale objects having dimensions in vitro to accelerate the kinetics of HA formation, mainly ranging from 1 nm to 100 nm. These are of particular sig- in the perspective of bone growth applications for dental nificance in a curative perspective. Hydroxyapatite (HA)- implants.14 Recently, modified single-walled carbon nano- based composites have shown swaying bioactivity. Howev- tubes (SWCNTs) have been shown to improve the flexural er, information on the influence of nanosized HA on the strength of RBCs. These SWCNTs had silicon dioxide properties of dental materials, especially dentin bonding applied to them in combination with specialized organo- adhesives, is yet insufficient. Nanorods having a nanosized silane bonding agents.15 Moreover, novel nanostructured HA adhesive system may have practical applications in titania tubes have been successfully introduced in the poly dental clinics. Chen et al have created enamel-prism-like (methyl methacrylate) (PMMA) bone cement matrix to 10 HA nanorods that have self-assembly properties. They enhance its mechanical properties (including high aspect are analogous to the enamel rods that construct the vital ratio), and fictionalization of the nanotubes allows them crystalline construction of dental enamel; therefore, to establish extended and strong interfacial adhesion.16 In nanorods may provide a convenient artificial model of this addition, the biocompatibility of carbon nanotube- naturally-occurring structure. Shojai et al synthesized HA reinforced bone cements seems to be challenging.17 nanorods with high crystallinity and high aspect ratio, Silica-doped high aspect-ratio TiO2 nanotube layers were which showed high dispersion stability in a dilute dental produced with different concentrations of silica particles experimental adhesive. HA nanorods may be regarded as an through anodization in NaCl electrolyte containing alternative to other fillers such as silicates for use in dental different concentrations of water glass (24 g/L or 48 g/L adhesives.11 Na2SiO3) by electrochemical anodic oxidation of Ti in chloride-containing electrolytes. The biomimetic apatite Nanospheres deposition behavior [under simulated body fluid (SBF)] showed successful silica doping of the resultant nanotube Similarly, nanospheres (Fig. 2C) have also been explored for layers with significant abundant OH groups on their sur- their potential evolution to curative systems to mimic faces. The results clearly demonstrate that the growth of

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL 4 S. Jain et al

Figure 2 Nanostructures used in dentistry: (A) nanoparticle; (B) nanorod; (C) nanosphere; (D) nanotube; (E) nanofibers; (F) dendrimers; (G) quantum dots; (H) nanopores; (I) nanocantilever; (J) nanoshell; (K) liposome; (L) nanoneedle.

HA on nanotubes that may be due to silica doping greatly Dendrimers and dendritic copolymers enhances the fast nucleation and growth of HA, especially for the tubes in their “as-formed” amorphous state, which Dendrimers (Fig. 2F) are perfect monodisperse macromol- usually require a long time for apatite induction. ecules with standard and highly branched 3D architecture. Dendrimers and dendritic copolymers have been less stud- ied than other nanostructures for dental composite appli- Nanofibers cations. Mixtures of specific polymers have been investigated to optimize effectiveness of restorative ap- plications.23,24 Photopolymerized dendritic copolymers and Nanofibers (Fig. 2E) are defined as fibers with diameters particulate filler composites have been combined for use as less than 1000 nm. These are explored for several dental restorative materials.24 Moreover, the incorporation biomedical applications.18 Currently, nanofibers are used to of polymerizable 2,3-dihydroxybenzyl ether dendrimers or produce ceramics containing HA and fluor-HA.19 Moreover, dendrons into dental composite resins produced dental nanofibrillar silicate crystals have been explored in their materials with enhanced physical properties.25 capability for strengthening dental composites, exclusively a mixture of the broadly employed 2ʹ-bis-[4-(methacrylox- ypropoxy)-phenyl]-propane (Bis-GMA) with triethylene gly- Quantum dots col dimethacrylate (TEGDMA) added as a thinning agent.20,21 Nanofibers were established to improve the Quantum dots (QDs; Fig. 2G) are typically semiconductor physical properties of these composites by addition in the nanocrystals that have gained tremendous attention due to correct proportion and with distribution of the fibers/ their unique electronic, magnetic, chemical, and optical crystals uniformly.20 The nanofibrous (NF)-poly(L-lactic properties. They have proven very useful in applications in acid) (PLLA) supported odontogenic differentiation of many fields across the physical, engineering, chemical, human dental pulp stem cells (DPSCs) and dentin-like tissue biological, and medical sciences, but especially in formation, demonstrating its potential for dental tissue dentistry.26 QD conjugates display important advantages engineering application.22 Nanofibers have a high aspect with standard epifluorescence microscopy, and brilliant ratio and a high surface area to volume ratio, which may single cell resolution of both in vitro and in vivo biofilm can lead to significantly enhanced physical and mechanical be achieved. The photostability of QD conjugates enables properties.17 micromanipulation of feasible spatially determined

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL Nanotechnology in the field of dentistry 5 communities from the enamel chip surface. Alves et al confirmed that liposomes adsorb to HA, which is the major studied dental resins impregnated with different concen- constituent of dental enamel.29 More recently, Nguyen et al trations of CdSe/ZnS coreeshell QD and found that QD core have investigated the potential of liposomes as a dental drug incorporation into dental resins allows the fabrication of delivery system, specifically for teeth targeting using in vitro restorative materials with fluorescence properties that adsorption of charged liposomal formulations to HA.30 They closely match those of natural human teeth.27 found that negatively charged liposomes were more effec- tive and were the least reactive with the components of Nanopores parotid saliva. The reactivity of negatively charged lipo- somes is based on the type of charge group bound to them. A nanopore (Fig. 2H) is simply a small hole, of the order of Calcium ion present in parotid saliva is a prerequisite for the 1 nm in internal diameter. Nanopore sequencing is one of interaction with negatively charged liposomes, and their the most promising technologies being developed as a affinity to the cations determines the degree of interaction. cheap and fast alternative to the conventional Sanger sequencing method. Protein or synthetic nanopores have Overview of nanomaterials used for dental been used to detect DNA or RNA molecules. Because DNA applications passes through a nanopore, scientists can observe the shape and electrical properties of each base, or letter, on Applications of in dentistry are especially the strand that can be effective in oral cancer detection promising, and areas such as disease diagnosis, drug de- and treatment.28 livery, specific drug targeting, and molecular imaging are being intensively investigated, with some products under- Nanoscale cantilevers going clinical trials.

Nanoscale cantilevers (Fig. 2I) are flexible beams resem- bling a row of diving boards. They are built using semi- Nanodentistry conductor lithographic techniques that can be engineered to bind to molecules associated with cancer. They may bind Novel possible treatment prospects in dentistry might to altered DNA sequences or proteins that are present in comprise local anesthesia, dentition renaturalization, a certain types of cancer and can provide rapid and sensitive permanent hypersensitivity cure, entire orthodontic re- detection of cancer-related molecules.29 As a cancer cell alignments through a single visit to the clinic, covalently secretes its molecular products (DNA sequences or pro- bonded diamondized enamel, and continuous oral health 31 teins), the antibodies coated on the cantilever fingers protection using mechanical dentifrobots. selectively bind to these secreted proteins, changing the physical properties of the cantilever and signaling the Nanocomposites presence of cancer. Nanocomposites are prepared by the uniform distribution Nanoshells of distinct nanoparticles in resins or coatings. Andrade et al tested fragments of nanofiller containing aluminosilicate Nanoshell materials have received considerable attention in (1:4 M ratio of alumina to silica) powder. These fragment recent years because of the potential applications associ- nanofillers had a mean particle size of 80 nm and 1.508 ated with them. These materials have a variety of applica- refractive index. Recently, a nanofill/nanohybrid compos- tions in dentistry including fluorescent diagnostic labels, ite has been found to show acceptable clinical performance 32 catalysis, avoiding photodegradation of teeth, enhancing in restorations of occlusal cavities of posterior teeth. photoluminescence, creating photonic crystals, and prepa- Moreover, the application of alumina-whisker-reinforced ration of bioconjugates. A nanoshell (Fig. 2J) is a type of composites in dental applications might be promising for spherical nanoparticle consisting of a dielectric core that is increasing hardness and fracture toughness compared with 33 covered by a thin metallic shell (usually gold). By modifying other materials. the core-to-shell ratio making up the nanoshells, scientists Dental resin nanocomposites containing CaF2 nano- can propose these shells to absorb near-infrared light particles that were developed with relatively high strength creating a powerful heat that is mortal to cancer cells. as well as sustained release of fluoride ions yielded resto- Nanoshells have a core of silica and a metallic outer layer.28 rations that reduce the occurrence of both secondary caries and restoration fracture.34 Nanocomposites show better Liposomes hardness, superior flexural strength, modulus of elasticity, and translucency, superior handling properties, and display The disadvantage that accompanies conventional drug de- a 50% decrease in filling shrinkage. livery systems is short retention time in the oral cavity because of salivation, irregular swallowing, food and Nanosolutions beverage intake, and abrasion by soft tissue movements. The use of liposomes as a dental drug delivery system is a A nanosolution is a unique dispersion of nanoparticles that new approach that might overcome this problem. Liposomes is generally used as a bonding agent. This ensures homo- (Fig. 2K) are vesicular structures with an aqueous core sur- geneity and also ensures that the adhesive is entirely mixed rounded by a lipid bilayer. In vitro experiments have all the time during bonding.

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL 6 S. Jain et al

Impression materials techniques could be used to check, suspend, or vary nerve impulse traffic in individual nerve cells in real time. Such For all impression materials, desirable properties include nanorobots may be prescribed by an on board nano- accuracy, dimensional stability, a pleasing smell and taste, computer that executes preprogrammed directives in the shortest setting time that is suitable for a given pro- response to local sensor stimuli. Nanorobotic dentifrice cedure, and easy removal of the set impression. The elas- (dentifrobots) transported by mouthwash or toothpaste at tomeric materials that are most frequently used are: least once a day can be used to protect supragingival and aqueous hydrocolloids (alginate and agar) and nonaqueous subgingival surfaces, metabolizing intended organic matter rubber (polysulfide, silicone, and polyether) materials. into safe and unscented vapors and performing uninter- 37 Nanofillers are incorporated in vinylpolysiloxanes, creating rupted calculus debridement. an exclusive addition of siloxane impression materials. The material has improved flow, enhanced hydrophilic proper- Dentin hypersensitivity cure ties, and better feature accuracy.35 Dentin hypersensitivity may occur due to the variation in Nanoencapsulation hydrodynamic pressure transmission to the pulp. This is based on the reality that hypersensitive teeth have eight The South West Research Institute (SWRI) Texas, United times more surface density of dental tubules and tubules of States, has urbanized targeted release systems that cover larger diameter compared to nonsensitive teeth. Conven- nanocapsules together with novel vaccines, antibiotics, and tionally, dental hypersensitivity is controlled or eradicated drug delivery with reduced side effects. Future focused by educating the patient regarding the undue intake of nanoparticles could be engineered to target oral tissues as acidic food, as well as providing guidance on the proper well as cells derived from the periodontium.35 Multilayer tooth brushing technique and analysis of occlusion. Effec- epoxy nanoencapsulants have a long history of medical tive treatment must be preceded by a proper diagnosis, applications in dentistry with their optimal use being im- established after the exclusion of any other possible causes plants with a medium-term (30 days to 6 months) lifespan. of the pain. These cases must be managed efficiently, A typical multilayer epoxy application might be a dental quickly, and permanently. Recently, reconstructive dental implant that measures moisture in a patient’s mouth, then nanorobots, using indigenous biological materials, could stimulates the submandibular gland to produce more saliva. selectively and precisely impede specific tubules within minutes, providing patients with a fast and lasting ther- apy.38 Moreover, dentin hypersensitivity can be treated by Nanorobotic dentifrice occlusion dentine tubules; open tubules are sealed and isolated from a peripheral stimulus, preventing fluid The use of conventional topical anesthetics does not movement from triggering a pain response.39 guarantee pain-free dental local anesthesia. The efficacy of conventional systems depends on the duration of applica- Dental plaque prevention tion and the gauge of the needle used. Recently, the introduction of a colloidal suspension having millions of dynamic analgesic micron-sized dental robots has proved It is accepted that dental plaque is mostly a complex bac- sufficient for performing intra-oral procedures, including terial biofilm. A wide variety of clinical studies has been periodontal manipulations, operative dentistry, and oral offered over the years to develop efficient strategies to surgery. Nanorobots are macroscale or microscale machines avoid and control periodontitis, such as antimicrobial that allow precision interactions with nanoscale objects mouth rinses. A plaque control mechanism to prevent caries that can be manipulated with nanoscale resolution. Their includes the following steps: (1) remove all plaque; (2) first useful application was in medicine to identify and reduce plaque levels below the threshold for disease; and destroy cancer cells but the most interesting applications (3) alter plaque pathogenicity. Possible approaches might may be in dentistry. Orthodontic nanorobots could openly therefore include: (1) mechanical removal of plaque; (2) influence the periodontal tissues, including gingivae, peri- the use of antimicrobial drugs either locally or systemically; odontal ligament, cementum, and alveolar bone, allowing (3) alteration in plaque biochemistry; (4) prevention of rapid and painless tooth straightening, rotating, and verti- bacterial attachment to the tooth surface; and (5) alter- cal repositioning within minutes to hours. This offers an ation of plaque ecology. To date, atomic force microscopy advantage over the molar uprighting techniques in current (AFM) is the foremost nanotechnology technique in use for use, which require weeks or months to complete. These analysis of cells and biofilm surfaces. AFM has been effec- nanorobots arrive at the pulp through the gingival sulcus, tively applied to explore nanometer-scale topographical changes resulting from the treatment of Streptococcus lamina propria, and dentinal tubules, and can be controlled 40 by dentists to protect the particular tooth from all sensa- mutans biofilms to various mouth rinse treatments. tions. After the completion of oral therapy, nanorobots can be used to renovate all sensations by improving nerve Dental implants passage.36 The first nanosized dental nanorobots were introduced for specific motility mechanisms to steal or Current trends in clinical dental implant therapy include swim through human tissue with navigational exactitude, the use of endosseous dental implant surfaces inflated with acquire energy, sense and manipulate their surroundings, nanoscale topographies. Implants using nanotechnology can and achieve safe cytopenetration; a combination of these effectively accelerate bone growth and increase

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL Nanotechnology in the field of dentistry 7 predictability. Nanoscale alteration of titanium endosseous sclerosis (MS) who have amalgam fillings, the levels of Rbcs, implant surfaces can change cellular and tissue responses hemoglobin, hematocrit, thyroxine (T4), T lymphocytes, and that may promote osseointegration and dental implant T8 (CD8) suppressor cells are significantly lower, while blood therapy. Moreover, the addition of nanoscale deposits of HA urea nitrogen and hair mercury levels are significantly and calcium phosphate produces a more complex implant elevated. Siblerud and Kienholz studied the hypothesis that surface for osteoblasts to form.41 Hg from silver dental fillings (amalgam) may be related to MS.44 They compared blood findings between MS subjects Tooth durability and appearance who had their amalgams removed to MS subjects with amalgams. MS subjects with amalgams were found to have The durability and appearance of teeth may be improved significantly trivial levels of Rbcs, hemoglobin, and hemato- by substituting upper enamel layers with covalently crit compared to MS subjects with amalgam removal. T4 bonded artificial materials such as sapphire or diamond, levels were further decreased in the MS amalgam group, and which have 20e100 times the hardness and strength of they had significantly lower levels of total T lymphocytes and natural enamel or modern ceramic veneers and good T8 (CD8) suppressor cells. The authors also examined biocompatibility. Like enamel, sapphire is fairly vulnerable epidemiological correlations between dental caries and MS to acid corrosion. Sapphire is the best standard whitening as well as how Hg could be causing the pathological and sealant and can be used as a cosmetic alternative. How- physiological changes found in MS. ever, sapphire and diamond are brittle and prone to fracture; this drawback can be overcome by the addition Safety aspects of nanotechnology of carbon nanotubes.42 Despite the numerous health and healthcare advances Nanoneedles provided by nanomaterials and nanotechnologies, several side effects have also been noted. The main health risks Scientists have achieved a subtle surgical operation on a related to the use of such devices consist of cytotoxicity, particular living cell, by means of a needle that is just a few translocation to undesired cells, acute and chronic toxicity, billionths of a meter wide. Nanoneedles are nanosized unpredictable and indeterminate safety concerns, and the stainless steel needles, which will make cell surgery environmental impact of nanomaterials and non- possible in the near future. Nanoneedles are marketed biocompatibility. Some nanoparticles show increased under the trade name of Sandvik Bioline, RK 91TM needles toxicity due to their increased surface area.43 Studies have (AB Sandvik, Sandviken, Sweden). Nanoneedles (Fig. 2L) shown carbon nanotubes to be cytotoxic and to induce can be used to deliver molecules such as nucleic acids, granulomas in the lungs of laboratory animals. Also, metals proteins, or other chemicals to the nucleus, or may even be and metallic oxide nanoparticles such as copper, cobalt, 43 used to carry out cell surgery. Using the nanoneedle titanium oxide, and silicon oxide have inflammatory and approach, we can get to a very specific location within the toxic effects on cells.45 There is an ongoing debate among nucleus; this is the key advantage of this method. researchers about the benefits and risks of nanotechnology. There are no exact Food and Drug Administration (FDA) Nanotweezers regulations for the control of nanotechnology-based ma- terials and allied problems. Overall, there is a critical The Danish research group (Nanohand) has developed requirement to standardize these nanotechnology-based nanotweezers, which can be used for both imaging and products and delivery devices. Characterization, safety, manipulation of nanosized objects to make cell surgery and environmental impact are the three main elements feasible in the near future. The dental research in the area that need to be regulated. However, regulatory agencies of single particle surveillance and manipulation, based on like the FDA, the Environment Protection Agency (EPA), and laser nanotweezer technology. In the continuation of the Nuclear Protection Agency are regulating the major research into manipulating carbon nanotubes inside scan- health risks associated with nanomaterials. Workers may be ning electron microscopes, 21st century nanosmiths have exposed to nanosized particles in the manufacturing or in- begun crafting a suite of research tools, including nano- dustrial use of nanomaterials; the National Institute for tweezers, nanobearings, and nano-oscillators. These nano- Occupational Safety and Health is performing research on 46 tweezer probes consist of two wires tapered consecutively nanoparticle interaction with body systems. through a nanopipette and kept electrically isolated.38 In vivo-used nonpyrogenic nanorobot materials include bulk teflon, carbon powder, and monocrystal sapphire. However, pyrogenic nanorobots include alumina, silica, and Dental composites and red blood cell (Rbc) trace elements such as copper and zinc. Moreover, the systems pyrogenic path of the intrinsic nanodevice surface is cir- cumvented by in vivo medical nanorobots. Nanorobots may Dental amalgam is an alloy of mercury with various metals liberate inhibitors, antagonists to the pyrogenic pathway, in used for dental fillings. It became the dental restorative a targeted manner to selectively take up the endogenous material of choice due to its low cost, ease of application, pyrogens, chemically alter them, and then release them strength, tolerance to a wide range of clinical placement back into the body in a harmless inactivated form.47 environments, and reasonable tolerance to the presence of The benefits of nanotechnology are enormous, therefore moisture during placement. In patients with multiple studies that examine the health, environmental, ethical,

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL 8 S. Jain et al and safety issues should improve our understanding of how 3. Freitas RA. Nanodentistry. J Am Dent Assoc 2000;131:1559e65. to exploit the benefits and diminish the risks. 4. Kumar SR, Vijayalakshmi R. Nanotechnology in dentistry. Ind J Dent Res 2006;17:62e5. 5. Rosin M, Schwahn C, Kordass B, Konschake C, Greese U, 48 Disputes faced by nanodentistry Teichmann D. A multipractice clinical evaluation of an ORMOCER restorativee2-year results. Quintessence Int 2007; These include: (1) economical nanorobot mass production 38:306e15. technique; (2) precise positioning and assembly of the 6. Karabela MM, Sideridou ID. Effect of the structure of silane coupling agent on sorption charactersistics of solvents by molecular-scale part; (3) biocompatibility; (4) simultaneous dental resin-nanocomposites. Dent Mater 2008;24:1631e9. coordination of activities of large numbers of independent 7. Xia Y, Zhang F, Xie H, Gu N. Nanoparticle-reinforced resin- micron-scale robots; and (5) social issues of public accep- based dental composites. J Dent 2008;36:450e5. tance, ethics, regulation, and human safety. 8. Mayworm CD, Camargo JSS, Bastian FL. Influence of artificial saliva on abrasive wear and microhardness of dental compos- ites filled with nanoparticles. J Dent 2008;36:703e10. Future prospects of nanotechnology in 9. Schulz H, Schimmoeller B, Pratsinis SE, Salz U, Bock T. Radi- dentistry opaque dental adhesives: dispersion of flame-made Ta2O5/SiO2 nanoparticles in methacrylic matrices. J Dent 2008;36:579e87. The future holds the prospect that dental practice will 10. Chen H, Clarkson BH, Sun K, Mansfield JF. Self-assembly of largely be performed using equipments and devices based synthetic hydroxyapatite nanorods into an enamel prism-like e on nanotechnology. Future specialized nanodentistry could structure. J Colloid Interface Sci 2005;288:97 103. 11. Shojai MS, Atai M, Nodehi A, Khanlar LN. Hydroxyapatite nano- be engineered to target oral tissues, including cells derived rods as novel fillers for improving the properties of dental ad- from the periodontium. Nanotechnology is predicted to hesives: synthesis and application. Dent Mater 2010;26:471e82. alter health care in dentistry in the following ways: (1) 12. Fincham AG, Moradian-Oldak J, Simmer JP. The structural novel methods for disease identification and avoidance; (2) biology of the developing dental enamel matrix. J Struct Biol therapeutic assortment customized to the patient’s profile; 1999;126:270e99. (3) drug delivery and gene therapy. 13. Fan Y, Sun Z, Wang R, Abbott C, Moradian-Oldak J. Enamel inspired nanocomposite fabrication through amelogenin su- pramolecular assembly. Biomaterials 2007;28:3034e42. Conclusion 14. Oh SH, Finones RR, Daraio C, Chen LH, Jin S. Growth of nano- scale hydroxyapatite using chemically treated titanium oxide New science and technologies are previously making their nanotubes. Biomaterials 2005;26:4938e43. way into all aspects of dental practice and have changed 15. Zhang F, Xia Y, Xu L, Gu N. Surface modification and micro- traditional approaches to diagnostics, risk assessment, structure of single-walled carbon nanotubes for dental resin- based composites. J Biomed Mater Res B Appl Biomater prevention, and many other procedures. The impact of 2008;86:90e7. nanotechnology on the field of dentistry is creating major 16. Khaled SMZ, Miron RJ, Hamilton DW, Charpentier PA, changes with respect to improvement of health, diagnosis, Rizkalla AS. Reinforcment of resin based cement with titania and proper use of natural resources. Nanotechnology has nanotubes. Dent Mater 2010;26:169e78. had its greatest effect on restorative dentistry by contrib- 17. Marrs B, Andrews R, Rantell T, Pienkowski D. Augmentation of uting to the enhancement of previously established clinical acrylic bone cement with multiwall carbon nanotubes. J Bio- RBC systems with the help of nanostructures such as med Mater Res 2006;77A:269e76. nanoparticles, nanotubes, nanorods, quantum dots, den- 18. Zhang Y, Lim CT, Ramakrishna S, Huang ZM. Recent develop- drimers, nanospheres, nanofibers, etc. Moreover, nano- ment of polymer nanofibers for biomedical and biotechnolog- e composites or nanomaterials are likely to have a greater ical applications. J Mater Sci Mater Med 2005;16:933 46. 19. Kim HW, Kim HE. Nanofiber generation of hydroxyapatite and role in material development for the dental trade. Nano- fluor-hydroxyapatite bioceramics. J Biomed Mater Res B Appl technology improves the understanding of the pathophysi- Biomater 2006;77:323e8. ologic basis of disease, conveys extra refinements in 20. Tian M, Gao Y, Liu Y, Liao Y, Hedin NE, Fong H. Fabrication and diagnosis, and yields more efficient treatment and pre- evaluation of Bis-GMA/TEGDMA dental resins/composites con- ventive properties. Nanodentistry has the potential to taining nano fibrillar silicate. Dent Mater 2008;24:235e43. preserve complete oral health with the use of nano- 21. Tian M, Gao Y, Liu Y. Bis-Gma/Tegdma dental composites materials, biotechnology (including tissue engineering and reinforced with electrospun nylon 6 nanocomposite nanofibers gene therapy), and dental . In the future it is containing highly aligned fibrillar silicate single crystals. Poly- expected that nanotechnology will develop into the core mer (Guildf) 2007;48:2720e8. technology underlying dentistry. 22. Wang J, Liu X, Jin X, et al. The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(L-lactic acid) scaffolds in vitro and in vivo. Acta Biomater 2010;6:3856e63. References 23. Viljanen EK, Langer S, Skrifvars M, Vallittu PK. Analysis of re- sidual monomers in dendritic methacrylate copolymers and composites by HPLC and headspace-GC/MS. Dent Mater 2006; 1. Murray CB, Kagan CR, Bawendi MG. Synthesis and character- 22:845e51. ization of monodisperse nanocrystals and closed-packed 24. Viljanen EK, Skrifvars M, Vallittu PK. Dendritic copolymers nanocrystal assembalies. Annu Rev Mater Sci 2000;30: and particulate filler composites for dental applications: degree 545e610. of conversion and thermal properties. Dent Mater 2007;23: 2. Paull R, Wolfe J, Hebert P, Sinkula M. Investing in nanotech- 1420e7. nology. Nat Biotechnol 2003;21:1134e47.

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004 + MODEL Nanotechnology in the field of dentistry 9

25. Paul NM, Bader SJ, Schricker SR, Parquette JR. 2,3-Branching 36. Meechan JG. Intra-oral topical anaesthetics: a review. J Dent benzyl ether dendrimers for the enhancement of dental com- 2000;28:3e14. posites. React Funct Polym 2006;66:1684e95. 37. Sumikawa DA, Marshall GW, Gee L. Microstructure of primary 26. Chalmers NI, Palmer RJ, Thumm LD, Sullivan R, Wenyuan S, tooth dentin. Pediatr Dent 1999;21:439e44. Kolebrander PE. Use of quantum dot luminescent probes to 38. Whitesides GM, Love JC. The art of building small. Sci Am 2001; achieve single-cell resolution of human oral bacteria in bio- 285:33e41. films. Env Microbiol 2007;73:630e6. 39. Cummins D. Dentin hypersensitivity: from diagnosis to a 27. Alves LP, Pilla V, Murgo DOA, Munin E. Coreeshell quantum dots breakthrough for everyday sensitivity relief. J Clin Dent 2009; tailor the fluorescence of dental resin composites. J Dent 2010; 20:1e9. 38:149e52. 40. Sharma S, Cross SE, Hsueh C, Wali RP, Stieg AZ, Gimzewski JK. 28. Burns JR, Stulz E, Howorka S. Self-Assembled DNA nanopores Nanocharacterization in dentistry. Int J Mol Sci 2010;11:2523e45. that span lipid bilayers. Nano Lett 2013;13:2351e6. 41. Albrektsson T, Sennerby L. State of the art in oral implants. J 29. Nguyen S, Solheim L, Bye R, Rykke M, Hiorth M, Smistad G. The Clin Periodontol 1991;18:474e81. influence of liposomal formulation factors on the interactions 42. Yunshin S, Park HN, Kim KH. Biologic evaluation of chitosan between liposomes and hydroxyapatite. Colloid Surface B nanofiber membrane for guided bone regeneration. J Perio- 2010;76:354e61. dontol 2005;76:1778e84. 30. Nguyen S, Hiorth M, Rykke M, Smistad G. The potential of li- 43. Dunphy GKA, Taylor MR, Banfield JF. Environmental risks of posomes as dental drug delivery systems. Eur J Pharm Bio- nanotechnology: national nanotechnology initiative funding, pharm 2011;77:75e83. 2000e2004. Environ Sci Technol 2006;40:1401e7. 31. Rybachuk AV, Chekman IS, Nebesna TY. Nanotechnology and 44. Siblerud RL, Kienholz E. Evidence that mercury from silver nanoparticles in dentistry. Pharmacol Pharm 2009;1:18e20. dental fillings may be an etiological factor in multiple sclerosis. 32. Andrade AKM, Duarte RM, Silva FDSCM, et al. 30-Month rand- Sci Total Environ 1994;142:191e5. omised clinical trial to evaluate the clinical performance of a 45. Cobb MD, Macoubrie J. Public perceptions about nanotechnology: nanofill and a nanohybrid composite. J Dent 2011;39:8e15. risks, benefits and trust. J Nanoparticle Res 2004;6:395e405.

33. Rascon AN, Elguezabal AA, Orrantia E, Bernal MBH. Al2O3(w)- 46. Roco MC. Nanoscale science and engineering educational ac- Al2O3(n)-ZrO2 (TZ-3Y)n multi-scale nanocomposite: an alter- tivities in the US. J Nanoparticle Res 2002;4:271e4. native for different dental applications. Acta Biomater 2010;6: 47. Chan KS, Lee YD, Nicolella DP, Furman BR, Wellinghoff S, 563e70. Rawls HR. Improving fracture toughness of dental nano- 34. Xu HHK, Moreau JL, Sun L, Chow LC. Strength and fluoride composites by interface engineering and micromechanics. Eng release characteristics of a calcium fluoride based dental Fract Mech 2007;74:1857e71. nanocomposite. Biomaterials 2008;29:4261e7. 48. Fakruddin Md, Hossain Z, Afroz H. Prospects and applications 35. Herzog A. Genomics O. Cyborgs and nanotechnology: a look of nanobiotechnology: a medical perspective. J Nanobiol 2012; into the future of medicine. Conn Med 2002;66:53e4. 10:31e8.

Please cite this article in press as: Jain S, et al., Nanotechnology: An emerging area in the field of dentistry, Journal of Dental Sciences (2013), http://dx.doi.org/10.1016/j.jds.2013.08.004