Nanotechnology in Dentistry: Clinical Applications, Benefits, and Hazards

Govind Shashirekha, MDS; Amit Jena, MDS; and Satyajit Mohapatra, MDS

The prefix nano emanated from the Greek word nanos, which means dwarf, and is used to describe materials whose molecular size lies in the range of 0 to 100 nanometers. One nanometer (nm) is one-billionth or 10-9 of a meter. Japanese scientist Dr. Nori Taniguchi in 1974 coined the term nanotechnology and defined it as “the processing of separation, consolidation, and deformation of materials by one atom or one molecule.”¹ The possibility of molecular engineering was first described by Nobel laureate physicist Richard Feynman in 1959 at the American Physical Society meeting at the California Institute of Technology in a lecture titled There’s Plenty of Room at the Bottom. In 1987, one-time student of Feynman K. Eric Drexler, published a book titled Engines of Creation-The Coming Era of Nanotechnology. In 1991 Sumio Iijima described carbon nanotubes in an article titled Helical Microtubules of Graphitic Carbon.²

Nanomaterials

Nanomaterials are materials whose component size ranges from 0 to 100 nm in at least one dimension. These materials may be present in the form of a cluster of atoms, grains, fibres, or films, or as nanoholes. Nanomaterials possess improved properties as compared to the parent material. The change is basically of two types: (1) due to increase in the surface area; and (2) quantum effects. As the material size approaches the nanoscale dimensions, a greater number of these nanoscale materials can be incorporated with the resultant increase in surface area.³ Quantum effects refer to the optical, electric, and magnetic properties that are altered when the material approaches the smaller end of the nanoscale.

Nanomedicine, Nanorobots, and Implantable Devices

The concept of nanomedicine was first introduced by Robert A Frietas, Jr. in 1993 and was defined, as follows: “Nanomedicine is the preservation and improvement of human health using molecular tools and molecular knowledge of the human body.”⁴ It has diversified actions ranging from target drug delivery to creating tissue scaffolds based on nanoscale molecules.

Nanorobots are about 0.5 µm to 3 µm in diameter and made of components in nanoscale dimensions. Carbon in the form of diamonds or fullerenes is the chief component. Once inside the target tissues, these nanorobots respond to definite programs. This gives the flexibility to control and execute procedures at the cellular and molecular level. Nanorobots have found their use into various areas of medicine, including pharmaceutics, diagnostics, gene therapy, and dentistry.⁵

Nano implantable devices are applied in various fields ranging from tissue regeneration materials, implantable devices, osseous repair, implant coating materials, bioresorbable materials, smart materials, tissue replacement materials, and diagnostic and therapeutic aids, to cochlear materials.

Approaches to Nanodentistry

In the top-down technique, larger devices are used to assemble smaller devices (Figure 1).¹ Milling, machining, and lithography are a few examples of this technique.⁶ The bottom-up technique refers to the use of smaller components into a more complex assembly. It involves the process of designing custom-made molecules that reorganize to higher scale structures. This method is most widely used as it proves to be more economical and cost effective.

Nanorobotic Local Anesthetics

Nanorobotic local anesthetics are composed of a colloidal solution of activated nanosized local anesthetic molecules. When applied to the gingival or the oral mucosa and signaled, the anesthetic travels via the epithelial and connective tissues of the gingiva to reach the pulp, thus providing selective anesthesia, which is under the control of the clinician. These ambulatory nano-active solutions are directed to the target site by chemical and temperature gradients. Upon reaching the pulp and establishing control over the nerve-impulse traffic, these nanorobots may be commanded to shut all neurosensory sensations to a particular tooth or multiple teeth as desired by the dentist. On completion of the procedure, the nanorobots may again be signaled to restore the sensation and, following this, they are aspirated. The advent of this technology offers greater patient comfort with minimal patient anxiety, precise selectivity, and controllability of the analgesic effect, as well as complete reversibility of the analgesic.⁷

Dentin Hypersensitivity

Reconstructive dental nanorobots are able to selectively and precisely block dentinal tubules, offering a quick and permanent cure. These nanorobots travel toward the dental pulp via the dentinal tubules. Desensitizing toothpaste containing 15% hydroxyapatite nanoparticles has been found to be effective in reduction of dentin hypersensitivity clinically even after single application for a period of 4 weeks.⁸

Dentifrobots

Dentifrobots are nanorobots incorporated into dentifrices and mouthwashes that help to clean organic residues by moving throughout the gingival tissues at a speed of approximately 10 microns/second, continuously preventing the accumulation of calculus. They can also be deactivated when accidentally swallowed by the patient.⁹ Dentifrobots can selectively identify and destroy pathogenic bacterial species in plaque biofilms and prevent halitosis.¹⁰

Nanodiagnostics

Nanoscale cantilevers: Flexible beams resembling rows of divided boards that bind to cancer-associated molecules.

Nanopores: These act as filters for DNA that allow only single strands of DNA to pass through them, thus allowing efficient DNA sequencing.

Nanotubes: These are nanosized carbon rods that are about half the diameter of a DNA molecule. They help to detect and identify the exact location of altered genes.

Quantum dots: These nanomaterials fluoresce when illuminated by ultraviolet light. When coated appropriately, they bind to proteins associated with cancer cells.

Nano Electromechanical Systems (NEMS): Nanotechnology-based NEMS biosensors are used for analyte detection. They help in converting (bio)chemical to an electrical signal.¹¹

Oral fluid nanosensor test (OFNASET): This technology helps detect salivary biomarkers for oral cancers. It incorporates self-assembled monolayers (SAM), bionanotechnology, cyclic enzymatic amplification, and microfluidics for detection of salivary biomarkers. In a study, 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) had high sensitivity and specificity in detection of oral cancer.¹²

Optical Nanobiosensor: These are minimally invasive, fiberoptic-based nanobiosensors that allow analysis of intracellular components and proteins.¹³

Lab-on-a-chip methods: Lab-on-a-chip combines various laboratory functions on a single chip. The analysis is done on chemically activated beads embedded onto silicon wafers. The advantage of this method includes a small sample requirement, short analysis time, and reduced cost. In dentistry, these have been used to assess the levels of interleukin-1 beta (IL-1ß), C-reactive protein (CRP), and matrix metalloproteinase-8 (MMP-8) in the whole saliva, which acts as biomarkers for diagnosing and categorizing the severity and extent of periodontitis.¹⁴

Nanomaterials

Nanocomposites: These are composite resins containing homogenously distributed nano-agglomerated nanoparticles. Aluminosilicate powder in 1:4 ratio is the most commonly used filler, with an average particle size of 80 nm.¹⁵ These nanofillers have a refractive index of approximately 1.503 and have advantages over conventional microfilled and hybrid resin-bonded composite (RBC) systems. These nanofilled composites have increased polishability, smoothness, flexural strength, and color characteristics compared to other posterior RBC.

Nanosolution (Nano adhesives): Nanosolutions manufactured using soluble nanoparticles when used in bonding agents lead to a homogenous and well-mixed adhesive consistently.¹⁶ They have high bond strength, long shelf-life, good marginal seal, fluoride release, and good stress absorption.^8,15

Nano Light-curing Glass-Ionomer Restorative: Application of nanotechnology to glass-ionomer cement (GIC) was first developed for Ketac™ Nano (3M ESPE, 3mespe.com) with fluor aluminum-silicate technology having nanoparticles in the range of 1 µm.¹⁷ The addition of nanoparticles resulted in improved esthetics and polishability of the restoration.¹⁸ Another nanofilled light-cured varnish (G-Coat Plus™, GC Europe, gceurope.com) is applied onto the surface of viscous GIC (Fuji IX GP® Extra, GC Europe). This commercial product is the EQUIA (Easy-Quick-Unique-Intelligent-Aesthetic) system, which contains inorganic silica nanofillers (15 wt. % and 40-nm size) dispersed in a liquid. Nanofillers resulted in improved wear resistance by avoiding initial water intake and dehydration and decreased initial setting time. Friedl et al¹⁹ in a retrospective study of nanomodified GICs evaluated their performance over conventional GICs and concluded EQUIA restorations to be superior. Earlier study of antimicrobial property of silver nanoparticles in GIC against Streptococcus mutans has shown to be highly effective in reducing the bacterial load.²⁰

Endodontic Sealers

Application of nanotechnology has been extended to the field of endodontics as well. Bioceramic-based sealer EndoSequence BC Sealer™ (Brasseler USA, brasselerusadental.com) containing calcium silicate, calcium phosphate, calcium hydroxide, zirconia, and a thickening agent, has been developed. The addition of nanoparticles resulted in improved handling and physical properties. When introduced into root canals, a hydration reaction occurs where a nanocomposite structure of calcium silicate and hydroxyapatite is formed. Water is essential for the setting reaction. Thus, in over-dried canals, setting time is prolonged.²¹ The addition of nanoparticles also facilitates delivery of material from 0.012 capillary needles and its adaption to irregular dentin surfaces. It sets hard in few hours and has good sealing ability along with dimensional stability. Its alkaline pH of (12.8) gives antimicrobial properties as well.^21,22

Silicon-based sealer containing gutta-percha powder and silver nanoparticles less than 30 µm in size has been introduced as well (GuttaFlow® 2, Coltene Whaledent, nam.coltene.com). It is available as capsules that can be mixed and injected as a cold flowable filling system.²¹ It has good biocompatibility and dimensional stability with good sealing ability and is resistant to bacterial penetration. Recently, antibacterial quaternary ammonium polyethyleneimine (QPEI) nanoparticles have been incorporated into other sealers (eg, AH Plus®, Dentsply DeTrey, dentsply.com; Epiphany®, Pentron Clinical Technologies, pentron.com; Guttaflow, Coltene), which are relatively stable, have good biocompatibility,²³ and resulted in good antibacterial activity without affecting mechanical properties.²⁴

Impression Materials

Nanofillers integrated into vinylpolysiloxanes resulted in impression materials with better flow, improved hydrophilic properties, and enhanced reproduction of surface details.²⁵

Nanocomposite Artificial teeth

Artificial composite teeth containing homogeneously diffused nanofillers have been reported to be superior to conventional acrylic teeth in terms of surface smoothness, abrasion resistance, and color stability.^26,27 Enhanced antifungal activity along with increased fracture toughness is seen in silver nanoparticle modified denture teeth.^28,29

Orthodontic Nanorobots

Orthodontic nanorobots could directly manipulate the periodontal tissues, thereby allowing a painless and rapid method for correcting malocclusion.³⁰

Nanomaterials for Tissue Regeneration

Nanobiomaterial-based tissue scaffolds are used for pulpal cell culture. Scaffolds based on nanofibers of biodegradable type I collagen or fibronectin are used for regeneration.^31,32 Pulp tissue regeneration is possible using self-assembling polypeptide hydrogels. The nanofiber mesh formed supported growing pulpal cells.³³ A study conducted by Misawa et al³⁴ has shown that cell growth was enhanced using Puramatrix containing repeats of essential amino acids (alanine, arginine, and aspartate). Other nanobiomaterials with potential dental applications for cell culture include natural silk³⁵ and an injectable self-assembling collagen-I scaffold, which when loaded with exfoliated teeth stem cells resulted in the formation of pulp-like tissue and functional odontoblasts.³⁶ Nanohydroxyapatite-based bone graft materials are also being used to treat large bone defects.³⁷

Nanomaterials for Periodontal Drug Delivery

Experimented nanomaterials explored for controlled drug delivery include nanotubes, hollow spheres, core-shell structure, and nanocomposite. Drugs incorporated into nanospheres of a biodegradable polymer allows for timed release of the drug.

Triclosan-loaded nanoparticles manufactured using poly(d,l-lactide-coglycolide), poly(d,l-lactide), and cellulose acetate phthalate was found to be effective in reducing periodontal inflammation.^38,39 Microspheres containing tetracycline are available as Arestin for controlled drug delivery into the periodontal pocket.¹⁰ An in vivo study observed nanostructured 8.5% doxycycline gel preserved the periodontal surface following experimentally induced periodontal disease in rats.⁴⁰

Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) is a relatively newly introduced treatment modality for removal of infectious pathogens. It uses a photosensitizer and light of a specific wavelength, eg, toluidine blue at 600-nm wavelength. Effective oral biofilm destruction with methylene blue dye (photosensitizer) encapsulated within poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (≈ 150 nm to 200 nm in diameter). A newly developed photosensitizer, indocyanine green (ICG), with loaded nanospheres when activated with 805-nm wavelength using a diode laser, has an a PDT-like effect and may serve as a potential photodynamic periodontal therapy.⁴¹

Implants

Surface characterizations of implant surfaces are increasingly being used to achieve higher success rates.⁴² The nanostructured implant coatings developed include (1) nanostructured diamond, with ultra-high hardness, improved toughness, low friction, and good adhesion to titanium alloys; (2) hydroxyapatite implant coatings manufactured using nanostructured processing, which has been found to increase the osteoblastic activity in terms of its adhesion, proliferation, and mineralization; and (3) nanostructured metalloceramic coatings on implant surface, which augments the osseointegration of dental implants by forming a nanocrystalline metallic bond with the implant surface and another hard ceramic bond on its surface.⁴³

Nanoneedles

Nanosized stainless steel crystals incorporated into commercially available needles have been developed (Sandvik Bioline 1RK91™, Sandvik, smt.sandvik.com). Current research is being conducted for the development of nanotweezers that would make cell surgery possible in the near future.¹⁵

Safety Issues

Nanobiomaterial technology is extensively being applied in healthcare services largely because of its various advantages. However, with increased use, concerns about the safety of these nanobiomaterials are being raised. The increased rate of absorption associated with manufactured nanoparticles is the main concern. Nanoparticles have an increased surface area:volume ratio, which leads to increased absorption of these particles through the skin, lungs, and digestive tract. Nonbiodegradable nanoparticles when accumulated within the body may be deposited in various organs and may lead to an unwanted reaction within biological tissues.

A study conducted by the Swedish Karolinska Institute revealed that iron-oxide nanoparticles were nontoxic on human lung epithelial cells and caused no DNA damage. Zinc-oxide nanoparticles were slightly worse. Titanium dioxide caused only DNA damage; carbon nanotubes caused DNA damage at low levels. Copper oxide was found to be highly toxic and was categorized as a health risk.⁴⁴

Conclusion

Advances in nanotechnology are paving the future of healthcare management. Nanodevices cannot be seen by the naked eye yet possess powerful capabilities. They have the potential to bring about significant benefits, such as improved health, better use of natural resources, and reduced environmental pollution. However, these nanodevices are also associated with significant potential misuse and abuse.

Nanodentistry aims to ensure comprehensive oral healthcare of the patient and emphasizes the primary prevention of oral diseases. With the availability of advanced and accurate diagnostic methods, a number of oral diseases can be prevented or treated at early signs.

Challenges in terms of basic molecular engineering methods, mass production techniques, and simultaneous coordination of a large number of nanorobots must be addressed prior to any large-scale application of nanotechnology.

Though the science of nanotechnology may appear as fiction in the present scenario, the future holds strong promise for utilizing and maximizing this technology for the benefit of mankind. Nanotechnology will change dentistry, healthcare, and human life profoundly. However, at the same time, social issues of public acceptance, ethics, regulation, and human safety will need to be addressed before molecular nanotechnology can enter the modern medical and dental armamentarium.

About the Authors

Govind Shashirekha, MDS
Professor
Department of Conservative Dentistry & Endodontics
Institute of Dental Sciences
Siksha ‘O’ Anusandhan University
Bhubaneswar, Odisha, India

Amit Jena, MDS
Professor and Department Head, Department of Conservative Dentistry & Endodontics
Institute of Dental Sciences, Siksha ‘O’ Anusandhan University
Bhubaneswar, Odisha, India

Satyajit Mohapatra, MDS
Private Practice
Cuttack, Odisha, India

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