Nanotechnology in orthodontics—1: The past, present, and a perspective of the future

Nanotechnology in orthodontics—1: The past, present, and a perspective of the future

CHAPTER Nanotechnology in orthodontics—1: The past, present, and a perspective of the future 11 Karthikeyan Subramani1, Usha Subbiah2 and Sarandeep...

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CHAPTER

Nanotechnology in orthodontics—1: The past, present, and a perspective of the future

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Karthikeyan Subramani1, Usha Subbiah2 and Sarandeep Huja3 1

Advanced Education in Orthodontics & Dentofacial Orthopedics, College of Dental Medicine, Roseman University of Health Sciences, Henderson, NV, United States 2Department of Human Genetics Laboratory, Sree Balaji Dental College and Hospital, Bharath Institute of Higher Education and Research, Chennai, India 3Department of Orthodontics, James B Edwards College of Dental Medicine, Medical University of South Carolina, Charleston, SC, United States

11.1 INTRODUCTION The concept and origin of nanotechnology have been attributed to the American physicist and Nobel Laureate Richard Phillips Feynman [1], who presented a paper titled “There’s Plenty of Room at the Bottom” on December 29, 1959, at the annual meeting of the American Physical Society at California Institute of Technology. Feynman proposed to employ machines to make smaller machine tools, which in turn could be utilized to make even smaller machine tools and so on, all the way down to the molecular and nanoscale level (1 nanometer 5 1029 meter or one-billionth of a meter). He suggested that such nanomachines, nanorobots, and nanodevices could be ultimately used to develop a wide range of atomically precise micro/nanoscopic instrumentation and manufacturing tools. Feynman also talked about the storage of information on a very small scale, writing and reading in atoms, miniaturization of computers, and building tiny machines and electronic circuits with atoms. He stated that “In the year 2000, when they look back at this age, they will wonder why it was not until the year 1960 that anybody began to seriously move in this direction.” However, Feynman did not specifically use the term “nanotechnology” then. The first use of the word “nanotechnology” has been attributed to Norio Taniguchi in a paper titled “On the Basic Concept of NanoTechnology” published in 1974 [2]. Eric Drexler, an MIT graduate took Feynman’s concept of a billion tiny factories and added the idea that they could replicate more copies of themselves, via computer control instead of a human operator in his 1986 book “Engines of Creation: The Coming Era of Nanotechnology” to popularize the potential of nanotechnology. Nanobiomaterials in Clinical Dentistry. DOI: https://doi.org/10.1016/B978-0-12-815886-9.00011-5 © 2019 Elsevier Inc. All rights reserved.

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Nanotechnology is described as the multidisciplinary science, which aims at the creation of materials, devices, and systems at the nanoscale level. It refers to the manipulation, precise placement, measurement, modeling, or manufacture of sub-100-nm scale matter. In other words, it has been described as the ability to work at atomic, molecular, and supramolecular levels (on a scale of B1 100 nm) to understand, create, and use material structures, devices, and systems with fundamentally new properties and functions resulting from their small structure. Nanotechnology has been approached in two ways: from the “top-down” or the “bottom-up” approach [3]. The “top-down” approach is nothing but the utilization of miniaturization techniques to construct micro/nanoscale structures from a macroscopic material or a group of materials by utilizing machining and etching techniques. The best example of a “top-down” approach is the photolithography technique used in the semiconductor industry to fabricate components of an integrated circuit by etching micro/nanoscale patterns on a silicon wafer. The “bottom-up” approach refers to the construction of macromolecular structures from atoms or molecules that have the ability to self-organize or self-assemble to form a macroscopic structure [4,5]. Nanotechnology has much more to offer than just simple miniaturization and building the molecular structures from the atomic scale. Over the past decade, numerous discoveries and applications of nanotechnology have revolutionized multiple disciplines of science, technology, medicine, and space exploration. In the field of medicine, nanotechnology has been applied in the diagnosis, prevention, and treatment of diseases. Nanomaterials are being applied in the field of pharmacotherapeutics toward new drug synthesis, targeted drug delivery for cancer treatment, regenerative medicine, imaging, and gene therapy [6,7]. Nanotechnology offers promising scope in dentistry to improve dental treatment, care, and prevention of oral diseases. Currently, numerous nanoscale dental materials, nanocharacterization methods, and nanofabrication techniques are being employed in dentistry to improve the biomaterial properties. During the last decade, the use of nanotechnology and nanoparticles has become popular in the design and development of dental biomaterials with improved material characteristics. The purpose of this chapter is to give the reader an overview of these recent developments in nanotechnology, nanomaterials, nanoscale imaging tools, and their applications in dentistry, and more specifically in orthodontics.

11.2 NANOINDENTATION AND ATOMIC FORCE MICROSCOPY STUDIES ON ORTHODONTIC BRACKETS AND ARCHWIRES Orthodontic brackets bonded to teeth provide the means to transfer force from the activated archwire to the teeth to facilitate tooth movement. Orthodontic brackets can be metallic [stainless steel (SS), titanium (Ti), or gold] or tooth-colored (plastic or ceramic). The surface characteristics [roughness and surface free energy

11.2 Nanoindentation and Atomic Force Microscopy Studies

(SFE)] of the brackets play a significant role in reducing friction and plaque (biofilm) formation. Micro- and nanoscale roughness of these brackets can facilitate early bacterial adhesion. Even though the surfaces of newly placed brackets are smoother, there can be changes in the surface roughness and SFE during the course of orthodontic treatment. A nanoindenter coupled with an atomic force microscope (AFM) has been traditionally used to evaluate nanoscale surface characteristics of biomaterials. They have also been used to evaluate mechanical properties like hardness, elastic modulus, yield strength, fracture toughness, scratch hardness, and wear properties by nanoindentation studies. AFM, also called scanning force microscopy, was developed in 1986, subsequently led to the invention of the scanning tunneling microscope (STM) [8]. Similar in operation to the STM, the AFM involves scanning a sharp cantilever tip across a sample surface while monitoring the tip sample interaction to allow the reconstruction of the three-dimensional surface topography. A typical AFM can provide resolutions of the order of 1 nm laterally and 0.07 nm (subangstrom) vertically. AFM has been utilized to look at the nanoscale dimension of the orthodontic armamentarium and the changes taking place during the course of treatment. Orthodontic brackets and archwires can undergo changes to surface characteristics during treatment due to the effects of food and oral hygiene habits and/or calcification (Fig. 11.1) [9]. AFM has been utilized as a tool to evaluate the surface roughness

FIGURE 11.1 AFM image of retrieved Ni Ti archwire exposed in oral cavity for 1 month, depicting rough surface produced by calcification on wire surface [9]. AFM, Atomic force microscope; Ni Ti, nickel titanium.

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of SS, beta-Ti, and nickel Ti (Ni Ti) wires [10]. In this study, AFM measurement of surface roughness reiterated the fact that the roughness influences the effectiveness of sliding mechanics, corrosion behavior, and aesthetics of orthodontic archwires. The effects of decontamination and clinical exposure on elastic modulus, hardness, and surface roughness of SS and Ni Ti archwires were evaluated using AFM coupled with a nanoindenter [11]. The results of AFM evaluation showed that the decontamination regimen and clinical exposure had no statistically significant effect on Ni Ti wires, but did have a statistically significant effect on SS wires. The study concluded that it is difficult to predict the clinical significance of these statistically significant changes in archwire properties on orthodontic tooth movement. Surface roughness of various orthodontic bracket slots before and after sliding movement of archwire in vitro and in vivo were observed quantitatively using AFM in a recent study [12]. Conventional SS, ceramic, self-ligating SS, and ceramic brackets were evaluated. In vitro sliding test results with beta-Ti wire in the conventional SS and ceramic brackets showed that there was a significant increase in surface roughness only in SS brackets. The results of surface roughness with AFM measurements on the brackets after a 2-year orthodontic treatment regimen showed that self-ligating ceramic brackets had undergone less significant changes in roughness parameters than self-ligating SS brackets. The study concluded that the self-ligating ceramic bracket has great possibility to exhibit low friction and better biocompatibility than the other tested brackets, including the conventional brackets. Such studies using AFM have shown that it can be utilized as an effective imaging tool to visualize and analyze the surface properties and understand the changes taking place at the nanoscale dimension of orthodontic wires or brackets during treatment.

11.3 FRICTION-REDUCING NANOCOATINGS ON ORTHODONTIC ARCHWIRES Orthodontic archwires are used to generate biomechanical forces that are transmitted through brackets to move teeth and correct malocclusion, spacing, and/or crowding. They are also used for retentive purposes, that is, to maintain teeth in their current position. Currently orthodontic archwires are fabricated from base metal alloys. The types of wires most commonly used are SS, Ni Ti, and beta-Ti alloy wires (composed of Ti, molybdenum, zirconium, and tin). When employing sliding mechanics, friction between the wire and the bracket is one of the primary factors influencing tooth movement. When one moving object contacts another, friction is introduced at the interface, which results in resistance to tooth movement. This frictional force is proportional to the force with which the contacting surfaces are pressed together and is governed by the surface characteristics at the interface (smooth/rough, chemically

11.3 Friction-Reducing Nanocoatings on Orthodontic Archwires

reactive/passive or modified by lubricants). Minimizing the frictional forces between the orthodontic wire and brackets will speed up desired tooth movement and therefore result in less treatment time. In recent years, nanoparticles have been used as a component of dry lubricants. Dry lubricants are solid-phase materials that are able to reduce friction between two surfaces sliding against each other without the need for a liquid media. Biocompatible nanoparticles have been coated on orthodontic SS wires to reduce friction. Inorganic fullerene-like nanoparticles of tungsten disulfide (IF-WS2) (Fig. 11.2), which are potent dry lubricants, have been evaluated as self-lubricating coatings for orthodontic SS wires [13]. In a recent study, orthodontic SS wire was coated with a nickel phosphorous (Ni P) film impregnated with IF-WS2 (Fig. 11.3) [14]. Coating was done by inserting SS wires into solutions of Ni P and IF-WS2. The coated wires were then analyzed by SEM (scanning electron microscope) and energy-dispersive X-ray spectrometer as well as by tribological tests using a ball-on-flat device. Friction tests simulating archwire functioning of coated and uncoated wires were carried out by an Instron machine. The adhesion properties of the coated wires after friction were analyzed using a Raman microscope. The frictional forces when measured on the coated wire were reduced by up to 54% when compared to uncoated SS wire. The friction coefficient was also significantly reduced from 0.25 to 0.08 (Fig. 11.4). These studies concluded that SS wires coated with these nanoparticles might offer a novel opportunity to substantially reduce friction during orthodontic tooth movement. It has been reported in animal studies that these nanoparticles are biocompatible [13]. A tungsten disulfide nanocoating has also

FIGURE 11.2 TEM lattice image of a typical IF-WS2 nanoparticle. Each dark line represents an atomic layer of the basal planes with a distance of 0.62 nm between the layers [14]. IF-WS2, Inorganic fullerene-like nanoparticles of tungsten disulfide.

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FIGURE 11.3 SEM image of an Ni P 1 IF-WS2-coated SS wire (right) and the same coating shown in large magnification (left). The impregnated IF nanoparticles are clearly visible in the Ni P film [14]. IF-WS2, Inorganic fullerene-like nanoparticles of tungsten disulfide; Ni P, nickel phosphorous; SEM, scanning electron microscope; SS, stainless steel.

FIGURE 11.4 Friction coefficient of the orthodontic wire substrate compared to a wire coated with Ni P and IF-WS2 [14]. IF-WS2, Inorganic fullerene-like nanoparticles of tungsten disulfide; Ni P, nickel phosphorous.

been evaluated for friction reduction of Ni Ti substrates (Table 11.1). Ni Ti substrates were coated with cobalt and an IF-WS2 nanoparticle film by electrodeposition procedure and the friction test results showed an up to 66% reduction of the friction coefficient on the coated substrates when compared to uncoated substrates [15]. The results of such studies may have potential applications in reducing the friction when using orthodontic Ni Ti wires. One drawback to the incorporation of Ni in these types of coatings is the potential for allergic

Table 11.1 Summary of Studies on Nanoparticle Applications in Materials Used in Orthodontics Material Studied

Nanoparticle/Nanoscale Imaging Technique Used

Orthodontic stainless steel wire [13,14]

Ni P film impregnated with IF-WS2 nanoparticles

Ni Ti substrates [15]

Parameters Evaluated

Results 1. Reduced to 54% on coated wires2. Friction coefficient reduced one-third from 0.25 to 0.08

Cobalt and IF-WS2 nanoparticles

1. Frictional forces measured on coated and uncoated wires2. Friction coefficient Friction coefficient

Stainless steel, beta-titanium and Ni Ti archwires [10]

AFM

Surface roughness

Stainless steel and Ni Ti archwires [11]

AFM coupled with nanoindenter

Effects of decontamination and clinical exposure on elastic modulus, hardness, and surface roughness

Conventional stainless steel, ceramic, self-ligating stainless steel and ceramic brackets [12]

AFM

Surface roughness

66% reduction in coated substrates Surface roughness influenced the effectiveness of sliding mechanics, corrosion behavior, and aesthetics Decontamination regimen and clinical exposure had no effect on Ni Ti wires, but did have a statistically significant effect on stainless steel wires. Decontamination of stainless steel wires significantly increased surface hardness (P 5 0.01) and reduced the surface roughness (P 5 0.02) Two-year orthodontic treatment regimen showed that self-ligating ceramic brackets had undergone less change in roughness parameters than self-ligating stainless steel brackets. Selfligating ceramic brackets exhibited low friction and better biocompatibility than other brackets (Continued)

Table 11.1 Summary of Studies on Nanoparticle Applications in Materials Used in Orthodontics Continued Material Studied

Nanoparticle/Nanoscale Imaging Technique Used

Parameters Evaluated

Results Highest values for CS, DTS, and BFS were found for NVPnanoceramic powder-modified cements (184 MPa for CS, 22 MPa for DTS and 33 MPa for BFS) Conventional orthodontic composite had higher shear bond strength than nanocomposite and nanoionomer groups

Fuji II GIC [25]

Nanohydroxy and fluoroapatite, NVP containing polyacids

CS, DTS, BFS

Nanocomposite material (Filtek Supreme Plus Universal) and the nanoionomer restorative material (Ketac N100 Light Curing NanoIonomer) and a conventional orthodontic composite material (Transbond XT) [28] ECA and two conventional adhesives (composite and resinmodified glass ionomer) [29]

Nanofilled composite material (Filtek Supreme Plus Universal) and GIC modified with nanofillers, and nanofiller “clusters” (Ketac N100 Light Curing NanoIonomer)

Shear bond strength

ECA was modified by the addition of silica nanofillers and silver nanoparticles

Effect of surface characteristics, physical properties, and antibacterial activities of ECA against cariogenic streptococci

BisGMA/HEMA adhesive modified with nanogel [30]

Nanogel copolymers at a 70:30 molar ratio of IBMA and either UDMA or BisEMA

Adhesive viscosity, wet mechanical properties, short-term micro-tensile bond strength

ECA had rougher surfaces than conventional adhesives due to addition of silver nanoparticles and bacterial adhesion to ECA was less than to conventional adhesives. No significant difference in shear bond strength and bond failure interface between ECA and conventional adhesives were noted Parameters evaluated were enhanced by nanogel inclusion in the adhesive resin

AFM, atomic force microscope; BFS, biaxial flexural strength; BisEMA, bis-phenol-adimethacrylate; CS, compressive strength; DTS, diametral tensile strength; ECA, experimental composite adhesive material; GIC, glass ionomer cement; IBMA, isobornyl methacrylate; IF-WS2, inorganic fullerene-like nanoparticles of tungsten disulfide; Ni P, Nickel phosphorous; Ni Ti, nickel titanium; NVP, N-vinylpyrrolidone; UDMA, urethane dimethacrylate.

11.4 Nanoparticles in Orthodontic Adhesives

reactions in patients with nickel sensitivity [16 19]. Therefore, the effect of such Ni P coatings on SS and Ni Ti wires should be evaluated for biocompatibility in animal models and further human trials.

11.4 NANOPARTICLES IN ORTHODONTIC ADHESIVES Composite materials and glass ionomer cements (GIC) have been primarily used in orthodontics as adhesive agents for securing orthodontic brackets and bands to the surface of the teeth. The largest application of nanoparticles has been in dental composite materials, where they have been used to enhance the long-term optical properties by virtue of their small size and at the same time provide superior mechanical strength and wear resistance. Ever since the first formulation of composite resins in the 1960s, the basic compositional triad has been used: monomer, silane-treated filler, and initiators. Filler particles improve the mechanical properties of the composite material. The filler used by Bowen in 1963 [20] consisted of milled quartz particles with average size ranging from 8 to 12 µm (8000 12,000 nm). Due to the aesthetic limitations of macrofilled composites (lack of surface gloss), the minifilled composite was introduced in the 1970s. Improvement in properties such as tensile and compressive strength, modulus of elasticity, abrasion resistance, radiopacity, aesthetics, and handling were noted with higher filler load. The filler material used was silica particles of average diameter of 400 nm, allowing a maximum filler loading of 55 wt.%, with better polishability, but with a significantly lower mechanical strength [21]. It was not until the 1980s and 1990s, that mixtures of filler materials were tested. These hybrid fillers (600 2000 nm) were commercialized as hybrid, microhybrid, and condensable composites [21]. There was an improvement in mechanical strength; however the polishability was still a limitation. A maximum filler load from 70 to 77 wt.% was recorded then. Micro-filled composites (10 100 nm) were not suitable for high stress-bearing areas (e.g., Class I, II, and IV restorations) of the dentition. The particle sizes of these hybrid composites were not similar to the size of the hydroxyapatite crystal, dentinal tubule, and enamel rod. There was also a potential for compromise in adhesion between the macroscopic restorative material and the nanoscopic (1 10 nm in size) tooth structure. Therefore, nanofilled composite materials were introduced. There are two distinct types of dental nanocomposites currently available: nanofills and nanohybrids [22,23]. Nanofills contain nanometer-sized particles (1 100 nm) throughout the resin matrix, with no other large primary particles included. Nanohybrids consist of larger particles (400 5000 nm) with added nanometer-sized particles. The use of nanoparticles addresses the aforementioned difficulty by combining high mechanical strength with long-term polish retention in one material. Another adhesive material used in orthodontics is GIC. GIC is also known as polyalkenoate cement and contains components of silicate glass and polyacrylic

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acid [24]. GIC is translucent and adhesive to tooth structure and has unique properties such as biocompatibility, anticariogenic action (due to fluoride release), and adhesion to moist tooth structure. In addition, the coefficient of thermal expansion for GIC is low and close to the values of tooth structure. Besides its advantages, GIC has some disadvantages such as brittleness and inferior mechanical strength. The use of GIC in orthodontics became popular during the late 1980s due to its fluoride-releasing potential, which made it highly attractive for orthodontic band cementation. It was shown that modifying conventional GIC with nanohydroxy and fluoroapatite (Fig. 11.5) and N-vinylpyrrolidone-containing

FIGURE 11.5 SEM of hydroxyapatite (A) and fluorapatite (B) nanopowders ( 3 40,000) [25]. SEM, Scanning electron microscope.

11.4 Nanoparticles in Orthodontic Adhesives

polyacids improved its mechanical properties. When tested, it proved to have greater compressive strength and higher diametral tensile strength and biaxial flexural strength than the control group consisting of conventional GIC [25]. Recently, “nanoionomer,” which is resin-modified GIC (Ketac N100 Light Curing Nano-Ionomer), has been introduced to operative dentistry [26,27]. This light-curing nanoionomer is composed of fluoroaluminosilicate glass, nanofillers, and nanofiller “clusters” combined to improve mechanical properties and high fluoride release. A recent study tested the commercially available nanocomposite material (Filtek Supreme Plus Universal) and the nanoionomer restorative material (Ketac N100 Light Curing Nano-Ionomer) for orthodontic bracket bonding [28]. The study evaluated their shear bond strength and failure site locations in comparison with a conventional light-cure orthodontic bonding adhesive (Transbond XT). Orthodontic brackets should withstand high shearing force in the oral cavity generated during the orthodontic teeth movement. The results of the study demonstrated that conventional orthodontic composite had higher shear bond strength than that of nanocomposite and the nanoionomer groups. The study concluded that nanocomposites and nanoionomers may be suitable for bonding, but are inferior to conventional orthodontic composites. In another study an experimental composite adhesive material (ECA) containing silica nanofillers and silver nanoparticles was compared with two conventional adhesives (composite and resin-modified glass ionomer) to evaluate the surface characteristics, physical properties, and antibacterial activity against cariogenic streptococci [29]. Bacterial adhesion was measured by incubating the adhesive discs for 6 hours in saliva sample. The discs were washed with sterile phosphate-buffered saline and the number of adherent cells was determined using a Beckman LS-5000TA liquid scintillation counter. The results of this study showed that ECA had rougher surfaces than conventional adhesives due to the addition of silver nanoparticles. However, the bacterial adhesion to ECA was less than with conventional adhesives. A bacterial suspension containing ECAs showed slower bacterial growth than those containing conventional adhesives. There was no significant difference in shear bond strength and bond failure interface between ECA and conventional adhesives evaluated in this study. It can be interpreted from the study that antibacterial nanoparticles can be incorporated into orthodontic adhesive materials to prevent bacterial adhesion and caries during orthodontic treatment. One of the current challenges in adhesive dentistry using hybrid materials is overhydrophilic bonding formulations, which facilitate water percolation through the hybrid layer resulting in unreliable bonded interfaces. A recent study evaluated a nanogel-modified dentin adhesive composed of BisGMA/ HEMA (2,2-bis [4(2-hydroxy-3-methacryloyloxy-propyloxy)-phenyl] propane/ 2-hydroxyethyl methacrylate) [30]. The nanogel additives of 10 100-nm-sized particles with varied hydrophobicity were synthesized in solution and added to BisGMA/HEMA. Nanogel copolymers at a 70:30 molar ratio of isobornyl

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methacrylate and either urethane dimethacrylate (less hydrophobic) or ethoxylated bis-phenol-adimethacrylate (more hydrophobic) was used. Adhesive viscosity, wet mechanical properties, short-term microtensile bond strength to acid-etched and primed dentin were studied. All these parameters evaluated were significantly enhanced in the nanogel-adhesive group over the control group containing just BisGMA/HEMA. These recent studies reinforce the importance of nanoscale-modified adhesive materials with improved properties for their use in orthodontics.

11.5 NANOPARTICLE DELIVERY FROM ORTHODONTIC ELASTOMERIC LIGATURES Fixed orthodontic appliance treatment significantly increases the risk of enamel decalcification and white spot lesions. These are caused due to prolonged accumulation and retention of bacterial plaque on the enamel surface adjacent to the attachments (orthodontic brackets and bands). Demineralization of enamel has been reported to occur around orthodontic brackets within 1 month of bracket placement in the absence of fluoride supplementation [31,32]. Elastomeric ligature ties have been conventionally used to hold orthodontic wires securely in the bracket during the treatment process. These elastomeric ligatures can serve as a carrier scaffold for delivery of nanoparticles that can be anticariogenic, antiinflammatory, and/or antibiotic drug molecules embedded in the elastomeric matrix. The release of anticariogenic fluoride from elastomeric ligatures has been reported in the literature previously [33 35]. The studies concluded that the fluoride release was characterized by an initial burst of fluoride during the first and second days, followed by a logarithmic decrease. For optimum clinical benefit, the fluoride ties should be replaced monthly [33]. These ties gained weight intraorally with residual, leachable fluoride present in fluoride-impregnated and nonfluoride elastomeric ligature ties after 1 month of intraoral use, due to imbibition [34]. An in vivo study evaluating the efficacy of fluoride-releasing elastomers in the control of colony-forming units (CFUs) of Streptococcus mutans in the oral cavity concluded that fluoride-releasing elastomeric ligature ties are not indicated for reducing the incidence of enamel decalcification in orthodontic patients. The study found no significant reduction in CFUs in saliva or plaque around the fluoride-releasing ties when compared with the conventional elastomeric ligature ties [35]. There are very few published studies evaluating the release and efficacy of nanoparticle-based anticariogenic, antiinflammatory, analgesic, or antibiotic drug delivery from orthodontic elastomeric ligatures to prevent enamel decalcification, decrease the biofilm accumulation during the orthodontic treatment, or reduce infections. Medicated wax applied to orthodontic brackets that

11.6 Development and Future Applications of Nanotechnology

slowly and continuously released benzocaine was shown to be significantly more effective in reducing pain associated with mucosal irritation caused by brackets [36]. It could be highly advantageous to explore the local delivery of such therapeutic nanoparticles at the site of enamel decalcification, biofilm formation, and gingivitis. As with all new technological applications, however, it will also be important to carefully evaluate the rate of release of such nanoparticles, ingestion, biocompatibility, and systemic toxicity level for these new nanotechnology-based applications.

11.6 DEVELOPMENT AND FUTURE APPLICATIONS OF NANOTECHNOLOGY IN DENTISTRY AND ORTHODONTICS The future of nanotechnology in orthodontics has potential to develop in a number of additional applications as well, including: (1) the use of tooth-colored, shape-memory polymers to aesthetically move teeth, (2) tooth movement using orthodontic nanobots that could directly manipulate periodontal tissues allowing rapid and perhaps painless movement, dentifrobots (nanobots in dentifrices) delivered through mouthwash or toothpaste to patrol supragingival and subgingival surfaces performing continuous plaque/calculus removal and metabolizing trapped organic matter, and (3) nano changes on the surfaces of TADs to increase their retention, but still allow them to be removed when no longer needed.

11.6.1 THE USE OF SHAPE-MEMORY POLYMER IN ORTHODONTICS Over the past decade, there has been an increased interest in producing aesthetic orthodontic wires to complement tooth-colored brackets. Shape-memory aesthetic polymer is an area of potential research. These are a class of stimuli-responsive materials, which have the capacity to remember a preprogrammed shape imprinted during the synthesis, can be reformed at a higher temperature to impart a desired temporary shape, and recover their original shape when influenced by a stimulus, such as heat, light, or a magnetic field [37,38]. Applications of nanoparticles in shape-memory nanocomposite polymers can increase thermal conductivity of the polymers [39,40]. These wires can also be made with clinically relevant levels of elastic stiffness. Once placed in the mouth, these polymers can be activated by the body temperature or photoactive nanoparticles activated by light and thus influence tooth movement. Future research directions in shape-memory nanocomposite polymers to produce aesthetic orthodontic wires can be of interesting potential in orthodontic biomaterial research.

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11.6.2 BIOLOGICAL MICROELECTROMECHANICAL SYSTEMS/ NANOELECTROMECHANICAL SYSTEMS FOR ORTHODONTIC TOOTH MOVEMENT AND MAXILLARY EXPANSION Microelectromechanical system (MEMS) devices are manufactured using similar microfabrication techniques as those used to create integrated circuits. They often have moving components that allow a physical or analytical function to be performed by the device in addition to their electrical functions. The biological MEMS (bioMEMS) are made up of micromachined elements usually on silicon substrates, including gears, motors, and actuators with linear and rotary motion for applications to biological systems. Implantable bioMEMS have been used as biosensors for in vivo diagnostics of diseases and as drug-delivery microchips [41 43]. Nanoelectromechanical systems (NEMS) are devices integrating electrical and mechanical functionality on the nanoscale level. Evidence suggests that orthodontic tooth movement can be enhanced by supplementing the mechanical forces with electricity [44,45]. Animal experiments indicated that when 15 20 µA of low direct current (dc) was applied to the alveolar bone by modifying the bioelectric potential, osteoblasts and periodontal ligament cells demonstrated increased concentrations of the second messengers cAMP and cGMP. These findings suggest that electric stimulation enhanced cellular enzymatic phosphorylation activities, leading to synthetic and secretory processes associated with accelerated bone remodeling. However, the intraoral source of electricity is a major problem that has to be addressed. It has been recently proposed that microfabricated biocatalytic fuel cells (enzyme batteries) can be used to generate electricity to aid orthodontic tooth movement [46]. An enzymatic microbattery, when placed on the gingiva near the alveolar bone, might be a possible electrical power source for accelerating orthodontic tooth movement. It is proposed that this device uses organic compound (glucose) as the fuel, and is noninvasive and nonosseointegrated. The enzyme battery can be fabricated with the combination of two enzyme electrodes and biocatalysts such as glucose oxidase or formate dehydrogenase to generate electricity (Fig. 11.6) [46]. However, there are several issues, such as soft-tissue biocompatibility and the effect of foods with different temperatures and pH ranges on the output of such a microfabricated enzyme battery, that need to be addressed. The use of microenzyme batteries has issues including enzyme stability, electron transfer rate, and enzyme loading, which result in shorter lifetime and poor power density. Nanotechnology has offered nanostructured materials like mesoporous media, nanoparticles, nanofibers, and nanotubes, which have been demonstrated to be efficient hosts of enzyme immobilization. When nanostructured conductive materials are used, the large surface area of these nanomaterials can increase the enzyme loading and facilitate reaction kinetics, and thus improve the power density of the biofuel cells. It is expected that the MEMS/NEMS-based system will be applied over the next few years to develop biocompatible powerful biofuel

11.6 Development and Future Applications of Nanotechnology

FIGURE 11.6 A schematic diagram of an oral biocatalytic fuel cell. In this system, the reaction occurring is: glucose 1 O2-gluconolactone 1 H2O/H2O2 generating electricity for enhancing orthodontic tooth movement [46].

cells, which can be safely implanted in the alveolus of the maxilla or mandible or in the palate to enhance orthodontic tooth movement or rapid maxillary expansion.

11.6.3 NANOROBOT DELIVERY FOR ORAL ANESTHESIA AND IMPROVED ORAL HYGIENE In 2000, Robert A. Frietas Jr. suggested that dental nanorobots can be utilized to induce oral anesthesia [47]. These nanorobots can be controlled by an onboard nanocomputer that executes preprogrammed instructions and can be delivered as a colloidal suspension containing millions of active analgesic micrometer-sized nanorobot particles on the patient’s gingiva. The nanorobots might use specific motility mechanisms to travel through human tissues with navigational precision, acquire energy, and sense and manipulate their surroundings. They might also achieve safe cytopenetration and use any of a multitude of techniques to monitor, interrupt, or alter nerve-impulse traffic in individual nerve cells [48]. Frietas also proposed that these nanorobots can be guided painlessly through the gingival sulcus, lamina propria, cementodentinal junction, dentinal tubules, and finally reach the pulp. Moreover, this journey can be directed by a combination of chemical

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gradients, temperature differentials, and even positional navigation, all under the control of the onboard nanocomputer. In turn, the nanocomputer would be directed by the dentist to induce anesthesia, for example, in a specific tooth that requires treatment. More futuristic applications have been proposed by Frietas on utilizing nanorobots to treat carious lesions, dentin hypersensitivity, and dentifrobots (nanorobots in dentifrices). These could be delivered through mouthwash or toothpaste and could patrol supra- and subgingival surfaces of teeth, performing continuous plaque/calculus removal and metabolizing trapped organic matter into harmless and odorless vapor [47]. He has also suggested that orthodontic nanorobots could directly manipulate periodontal tissues, allowing rapid, painless tooth movement and repositioning within minutes to hours. However, it should be noted that inflammation and bone remodeling govern the rate of orthodontic tooth movement. The idea of achieving orthodontic tooth movement within minutes to hours looks futuristic considering the time required for the biological adaptation and remodeling processes of the periodontium that accompanies orthodontic treatment.

11.7 TEMPORARY ANCHORAGE DEVICES While temporary anchorage devices (TADs) have become increasingly utilized by orthodontic professionals to assist in the process of moving teeth, commercially available TADs exhibit a success rate of 60% 75% [49 51]. Currently TADs are manufactured with smooth Ti surfaces [pure Ti or Ti alloy (Ti 6Al 4V)] because complete osseointegration is a disadvantage that complicates their removal. On the other hand, lack of osseointegration is also one of the factors for failure of TADs. The success of TADs also depends on other factors like proper initial mechanical stability and loading quality and quantity. Clinically, there are difficulties encountered in the removal of TADs due to increased osseointegration even on the smoother-surface TADs. Therefore, it is postulated that the balance lies in the fabrication of an ideal surface that could stimulate initial osseointegration and facilitate its removal once the TAD is no longer needed. Biocompatible coatings like Ti nanotubes should be studied to evaluate whether the nanotubular layer can enhance initial osseointegration and serve as an interfacial layer between the newly formed bone and the TAD. A recent study evaluated the effects of surface roughness and carboxyl functionalization of multiwalled carbon nanotubes (MWCNTs) mixed with collagen coated onto Ti substrates [52]. The proliferation, differentiation, and matrix mineralization of MC3T3-E1 osteoblasts were investigated in this study for applications in orthodontic miniscrew implants (MSIs). (1) Smooth surfaced Ti discs, (2) Ti discs coated with collagen and MWCNTs (Ti-MWCNTs), and (3) Ti discs coated with collagen and MWCNT-COOH (Ti-MWCNT-COOH) were used in this study. It was observed that the coatings were uniform when analyzed using

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SEM. Surface profilometry showed that the MWCNT- and MWCNT-COOHcoated groups had similar surface roughness (Ra, mean 6 SE) of 0.83 6 0.006 µm and 0.83 6 0.007 µm, respectively. MTT assay was performed after days 1, 3, and 7 to assess proliferation. Alkaline phosphatase (ALP) activity was performed after days 7 and 14 to assess differentiation and Alizarin red staining was done after day 28 to measure matrix mineralization. After days 7 and 14, ALP activity assay results showed that MWCNT coatings (ALP/ protein 5 1.19) and presence of COOH group (ALP/protein 5 1.21) increased cell differentiation. Alizarin red staining after 28 days of cell culture revealed that the presence of COOH [(mean 6 SE) 1.47 6 0.01] increased matrix mineralization when compared to the MWCNT group [(mean 6 SE) 1 6 0.2]. This study showed that coatings containing MWCNT (increase in surface roughness) and MWCNT-COOH (more hydrophilic surface chemistry) influenced osteoblast proliferation and enhanced differentiation and matrix mineralization and such coatings should be further studied for applications in orthodontic MSIs.

11.8 CONCLUSIONS The applications of nanotechnology and nanoparticles have offered biomaterial scientists the opportunity to fabricate materials with improved physical and mechanical properties. The field of dental biomaterials is constantly evolving. The addition of such nanoparticles to currently available materials enhances their properties and clinical use. The applications of nanotechnology in orthodontic materials have been reported in the literature over the past few years. However, the number of studies specifically addressing orthodontics and nanotechnology are very low. The authors expect that the next decade will bring an increase in the amount and quality of research that will help unveil the next generation of nanomaterials for orthodontic treatment. There are many avenues yet to be explored that would help move MEMS/NEMS-based systems in orthodontics from the drawing board to the bench top and clinical study arena. The utilization of nanoparticles for improving TADs should be one such avenue.

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