Nanotechnology in orthodontics—2: Facts and possible future applications

Nanotechnology in orthodontics—2: Facts and possible future applications

CHAPTER Nanotechnology in orthodontics—2: Facts and possible future applications 12 Tarek El-Bialy The University of Alberta, Edmonton, AB, Canada ...

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CHAPTER

Nanotechnology in orthodontics—2: Facts and possible future applications

12 Tarek El-Bialy

The University of Alberta, Edmonton, AB, Canada

12.1 INTRODUCTION Nanotechnology involves the creation, manipulation, and use of materials and devices at the size scale of ,100 nm. It describes the technique of creating and using devices and components comparable in size to molecules and intracellular architecture [1]. Nanotechnology is progressing well in many biological sciences including medicine, pharmacy, and dentistry. In general dentistry, nanotechnology has potential to be applied in the management of teeth hypersensitivity, anesthesia, production of more enhanced dental products, and in orthodontic treatment [2]. This chapter presents the current status of the use of nanotechnology and nanoanalysis and three possible future applications in orthodontics. These applications involve nanoscale study of the topography of different orthodontic materials to evaluate their nanocharacteristics or nanomechanical properties. The possibility of nanogene therapy to enhance generation or to modify growth of different craniofacial structures is discussed. In addition, a nanofabricated ultrasound device for orthodontics is a future direction that would change the profile of dentofacial regeneration including possible prevention and treatment of orthodontically induced root resorption or dentoalveolar fracture.

12.2 NANOSCALE IN ORTHODONTICS One of the known challenges in orthodontics is bond failure of orthodontic attachments, including orthodontic brackets and tubes. In order to minimize bond failure, many attempts have been introduced to enhance the strength of orthodontic bonding composites. One of these attempts was to introduce nanocomposites and nanoionomers [3]. The introduction of nanofiller components originally was introduced to enhance some physical properties of the hardened restorative composites. Because of the decreased dimension of the particles in the nanofillers, Nanobiomaterials in Clinical Dentistry. DOI: https://doi.org/10.1016/B978-0-12-815886-9.00012-7 © 2019 Elsevier Inc. All rights reserved.

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a wide size distribution and increased filler load are achieved, which decreases polymerization shrinkage [4], and increases mechanical strength and resistance to fracture. In addition, it has been reported that nanocomposites had a good marginal seal to enamel and dentine compared with total-etch adhesives [5]. Since these nanofillers containing resin-modified glass ionomer cements (Ketac N100) were reported to have improved physical properties, as well as increased fluoride release than other restorative materials, it has been suggested they be used as a bonding material for orthodontic attachments. The increased fluoride release by nanofiller bonding materials compared to other restorative materials makes them more attractive in orthodontics since demineralization of the labial surfaces of teeth during orthodontic therapy is one of the major challenges facing orthodontists and orthodontic patients, especially in patients with compromised oral hygiene. However, although the results of using such a nanocomposite and nanoionomer bonding system may be suitable for bonding since they fulfill the suggested ranges for clinical acceptability, they are inferior to a conventional orthodontic composite [3]. There may be ongoing attempts to enhance the bonding strength of these nanocomposite and nanoionomer bonding systems to utilize their high fluoride release property in order to make them at least comparable in bond strength to conventional orthodontic bonding systems. Because of the increased awareness of enamel demineralization around orthodontic attachments, different materials have been used to minimize enamel demineralization. The effectiveness of these materials has been evaluated using atomic force microscopy (AFM) measurements that quantitatively evaluate nanoscale enamel surface roughness after using these materials [6] (Fig. 12.1).

FIGURE 12.1 AFM of human enamel treated by acid etching only showing narrow grooves (black arrows) and flattened perikymata ridges (white arrows) with cracks and many destroyed areas of nontreated enamel surface (A); enamel treated with acid etching and fluoride varnish showing moderately wide perikymata groove (black arrow) and localized areas of destruction (white arrows) (B); enamel treated with acid etching and unfilled sealant group showing wide perikymata grooves and flattened perikymata ridges (C); and enamel treated with acid etching followed by proseal showing perikymata ridge and groove with obvious focal holes (D) (frames are 50 3 50 µm). AFM, Atomic force microscopy. Reproduced from S.F. Shinaishin, S.A. Ghobashy, T.H. El-Bialy, Efficacy of light-activated sealant on enamel demineralization in orthodontic patients: an atomic force microscope evaluation, Open Dent. J. 5 (2011) 179186.

12.3 Nanotechnology and Gene Therapy in Orthodontics

FIGURE 12.2 Because all surfaces have irregularities that are large on a molecular level, real contact occurs only at peaks of irregularities, called asperities. When interlocking occurs between the peaks and bottoms of the asperities, resistance to movement occurs [7].

Orthodontic treatment may involve removal of some teeth to alleviate dental crowding or to treat some types of malocclusions. Closing extraction spaces usually requires moving bracketed teeth along arch wires made from different types of materials using sliding (also known as arch-guided) tooth movement. The friction between orthodontic brackets and wires, especially with a combination of metals, sometimes affects the efficiency of tooth movement. Also, friction in orthodontics has contributed to loss of anchorage due to application of increased forces to overcome friction between the brackets and wires. Increased friction between orthodontic wires and bracket surfaces has been attributed to micro/nanoasperities or mechanical interlocking at the micro or nanolevels [7] (Fig. 12.2). For this purpose, nanotechnology has been introduced to study different orthodontic wires and bracket slots to evaluate nanomechanical properties and the topographic pattern of these materials in order to understand factors affecting friction between orthodontic wires and brackets. However, the exact measurements of these micro/nanoasperities have only been evaluated using AFM. AFM allows for quantitative evaluation of the nanoscale surface roughness of various orthodontic bracket slots before and after sliding movement of archwire in vitro and in vivo [8].

12.3 NANOTECHNOLOGY AND GENE THERAPY IN ORTHODONTICS Mandibular underdevelopment has been attributed to a variable interaction of genetic and environmental factors, which is believed to be difficult to manipulate or stimulate. Bite-jumping appliances, also known as functional appliances (FAs),

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have long been claimed and used to enhance mandibular growth in cases with deficient mandibles (mandibular retrognathism). A recent study systematically reviewed reports on the effectiveness of FAs and concluded that the analysis of the effect of treatment with FAs versus an untreated control group showed skeletal changes that were statistically significant in the short term, but unlikely to be clinically significant [9]. It has been reported that rat condylar growth can be significantly increased by local gene therapy with recombinant adenovirus-associated virus (rAAV)mediated vascular endothelial growth factor, which is an important angiogenic mediator in vascularization and endochondral ossification [10]. Although the rAAV vector for gene delivery is proven to be a strong and effective vector, its use in human patients is facing controversial and ethical issues. There is a growing emphasis on nanotechnology in cancer detection and treatment (http://nano. cancer.gov). For example, nanovector liposomes have been used successfully in breast cancer therapy [11]. Regardless of its successful use, nanobiotechnology is still at an early stage of development and its use in treatment of diseases other than cancer could be especially challenging. The challenges facing these nanovectors might not have viable applications, especially in mandibular growth stimulation and could end up on the “technology shelf” in the future [12].

12.4 NANOFABRICATED ULTRASOUND DEVICE FOR ORTHODONTICS In translational research, proof of concept is usually the first step in testing the viability of new technology for potential treatment of any disease. We and other researchers have shown in proof of principle the efficacy of utilizing LIPUS in stimulating mandibular growth in growing animals and in human patients [1316]. One of the main challenges we faced when a pilot clinical trial was conducted to stimulate mandibular growth in humans with hemifacial microsomia was that the patients (young adults) needed to hold the LIPUS transducers (applicators) to their mandibular condyles for 20 minutes every day for at least 1 year in order to achieve clinical improvement of the deficient side of the mandible. This created a great challenge and burden on the parents to do this for that extended period of time. In order to minimize errors in LIPUS application and maximize consistency in treatment a noncompliant LIPUS application is in high demand. In addition, we have shown that LIPUS application to orthodontically moving teeth can minimize root resorption [17]. External apical root resorption (EARR) concurrent with orthodontic treatment is widely accepted as a risk in all types of orthodontic treatment appliances. Challenges in using LIPUS intraorally in the treatment of EARR concurrent with orthodontic treatment, include that the size of commercially available LIPUS transducers is quite large (3.5 cm3), difficult to adjust, and larger than any human tooth. In addition, the patients have to

12.5 Nanomechanical Sensors for Orthodontic Forces

FIGURE 12.3 (A) Large-scaled LIPUS device; (B) future nanofabricated intraoral LIPUS device.

hold the LIPUS transducers tightly against the gingiva of the corresponding tooth/ teeth for 20 minutes per day for at least 4 weeks in order to achieve a clinically noticeable decrease in EARR concurrent with orthodontic treatment. Because of these challenges there are needs for noncompliant LIPUS devices that can be inserted into the patient’s mouth and deliver the predesigned LIPUS treatment to the tooth/teeth in question. In order to build an intraoral LIPUS device that is independent of power supply or patient compliance, a nanocircuit design has been incorporated in order to nanofabricate the main operation circuit, as well as LIPUS transducer controller. In addition, a nanofabricated battery is required in a nanoscale intraoral LIPUS device. The first step in this nanodesigned LIPUS device was the nanofabrication of the operation circuit that delivers the required signal to the LIPUS transducer. This step has been developed by our group and tested for its validity to be potentially used for future nanofabricated LIPUS transducers and devices [18]. A future nanofabricated LIPUS device is compared to the original large-scaled device in Fig. 12.3.

12.5 NANOMECHANICAL SENSORS FOR ORTHODONTIC FORCES AND MOMENTS MEASUREMENT Orthodontic forces and moments are an undetermined force system due to many factors that are involved, including the orthodontic wire materials (that affect its modulus of elasticity) and geometry (that affects its stiffness). Both modulus of elasticity and geometry are important in determining wire stiffness according to the following equation (Figs. 12.4 and 12.5): K ðstiffnessÞ 5 E 3 I ðE: modulus of elasticity; I: is the area moment of inertiaÞ

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FIGURE 12.4 Wire diameter (d). For round wire;

π d4 I5 64



FIGURE 12.5 Rectangular wire base (b) and height (h). For rectangular wire;

I5

b h3 12



In addition, wire stiffness is also dependent on the wire length, which is determined intraorally by the interbracket distance. The smaller the bracket width, the greater the interbracket distance and the lower the wire stiffness according to the following equation: K ðstiffnessÞ

α1 L3

where L is the interbracket distance or wire length (Fig. 12.6). All the above factors affect the stiffness of the wire and consequently the force applied to the teeth. Since any small changes in wire length or diameter/crosssection can change the wire stiffness and consequently the applied force by this wire, it is almost impossible to predict the exact amount of force applied by the same wire to two different patients due to the difference in teeth crown widths, resulting in variation in interbracket wire lengths, and consequently applying

12.5 Nanomechanical Sensors for Orthodontic Forces

FIGURE 12.6 Interbracket distance between the maxillary left canine and maxillary left lateral incisor (yellow line) is less than that between maxillary left central incisor and maxillary left lateral incisor (blue line). The longer wire segment is more flexible than the shorter one.

different forces using the same type, shape, and size of wire. What complicates this process further is that the moments applied to the teeth are the result of multiplication of the magnitude of force times the perpendicular distance between the centers of resistance of the tooth to the line of action of the applied force (Fig. 12.7). Since the teeth root lengths are different among individuals, this consequently changes the length of the moment arms and the applied moments using similar forces. In order to apply biologically tolerable forces and moments to the teeth to efficiently move teeth with minimal adverse effects, such as EARR, depending on the individual’s intrinsic susceptibility, researchers have been working to develop brackets that can carry three-dimensional mechanical sensors in the bracket bases to measure in three dimensions the real-time forces and moments applied to the teeth. This would facilitate the orthodontist adjusting these forces should they exceed biologically acceptable limits. In order to achieve this, microsensors have been proposed in the recent literature. Lapatki et al. in 2007 reported on the introduction of a “smart” bracket for multidimensional force and moment measurement [19,20]. They reported on a large-scale prototype bracket that utilized microsystem chip encapsulation. Development of a nanosystem chip that can be encapsulated into small low-profile contemporary bracket systems with reduced mesio-distal and occlusogingival dimensions will allow clinical testing of the utilization of this technology.

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FIGURE 12.7 The moment produced by the force (F) equals the magnitude of the force F (100 g) multiplied by the perpendicular distance between the center of resistance and the line of action of the force (x 5 10 mm).

12.6 FUTURE APPLICATIONS OF NANOTECHNOLOGY IN ORTHODONTICS Although nanotechnology application in orthodontics is considered to be in its infancy, there is huge potential for application of nanotechnology in orthodontics, including nanodesigned orthodontic bonding materials, possible nanovectors for gene delivery for mandibular growth stimulation, and nano-LIPUS devices. Also, nanomechanical sensors can be fabricated and incorporated into the base of orthodontic brackets and tubes in order to provide real-time feedback about the applied orthodontic forces. This real-time feedback allows the orthodontist to adjust the applied force to be within a biological range to efficiently move teeth with minimal side effects. In a fast-growing world of nanotechnology, the hope would be to get these technologies into clinical application sooner than later. However, financial burden in developing and application of such technologies is a road block that requires special funding programs from major funding agencies and organizations.

12.7 CONCLUSIONS In conclusion, the future in orthodontic treatment will rely mainly on nanotechnology should all the current attempts succeed in its clinical application at a reasonable cost to the orthodontist and patients. It is recommended that appropriate research funds be allocated to orthodontic and dentistry nanotechnology research and development to help take these technologies to the clinical trial phase.

References

ACKNOWLEDGMENT The author would like to thank the authors who provided permission to use their published figures in this chapter.

REFERENCES [1] M.A. Zarbin, C. Montemagno, J.F. Leary, R. Ritch, Nanomedicine in ophthalmology: the new frontier, Am. J. Ophthalmol. 150 (2010) 144162. e2. [2] F.J. Leary, Nanotechnology: what is it and why is small so big? Can. J. Ophthalmol. 45 (5) (2010) 449456. [3] T. Uysal, A. Yagci, B. Uysal, G. Akdogan, Are nano-composites and nano-ionomers suitable for orthodontic bracket bonding? Eur. J. Orthod. 32 (2010) 7882. [4] N. Moszner, U. Salz, New developments of polymeric dental composites, Prog. Polym. Sci. 26 (2001) 535576. [5] S. Geraldeli, J. Perdigao, Microleakage of a new restorative system in posterior teeth, J. Dent. Res. (special issue A) (2003) 126 (Abstract). [6] S.F. Shinaishin, S.A. Ghobashy, T.H. El-Bialy, Efficacy of light-activated sealant on enamel demineralization in orthodontic patients: an atomic force microscope evaluation, Open Dent. J. 5 (2011) 179186. [7] W. Proffit, Contemporary Orthodontics, fifth ed., Elsevier, 2012, p. 329. [8] G.J. Leea, K.H. Parkc, Y.G. Parkc, H.K. Park, A quantitative AFM analysis of nanoscale surface roughness in various orthodontic brackets, Micron 41 (2010) 775782. [9] E. Marsico, E. Gatto, M. Burrascano, G. Matarese, G. Cordasco, Effectiveness of orthodontic treatment with functional appliances on mandibular growth in the short term, Am. J. Orthod. Dentofacial. Orthop. 139 (1) (2011) 2436. Review. [10] A.B. Rabie, J. Dai, R. Xu, Recombinant AAV-mediated VEGF gene therapy induces mandibular condylar growth, Gene Ther. (2007). [11] J.W. Park, Liposome-based drug delivery in breast cancer treatment, Breast Cancer Res. 4 (3) (2002) 9599. [12] P. Fortina, L.J. Kricka, S. Surrey, P. Grodzinski, Nanobiotechnology: the promise and reality of new approaches to molecular recognition, Trends Biotechnol. 23 (4) (2005) 168173. [13] R. Oyonarte, M. Za´rate, F. Rodriguez, Low-intensity pulsed ultrasound stimulation of condylar growth in rats, Angle Orthod. 79 (5) (2009) 964970. [14] T. El-Bialy, I. El-Shamy, T.M. Graber, Growth modification of the rabbit mandible using therapeutic ultrasound: is it possible to enhance functional appliance results? Angle Orthod. 73 (6) (2003). [15] T.H. El-Bialy, A. Hassan, T. Albaghdadi, H.A. Fouad, A.R. Maimani, Growth modification of the mandible using ultrasound in baboons: a preliminary report, Am. J. Orthod. Dentofacial. Orthop. 130 (10) (2006). 435 e7435 e14. [16] T. El-Bialy, A.H. Hassan, A. Alyamani, T. Albaghdadi, Treatment of hemifacial microsomia by therapeutic ultrasound and hybrid functional appliance. A nonsurgical approach, Open Access J. Clin. Trials 2 (2010) 2936. [17] T. El-Bialy, I. El-Shamy, T.M. Graber, Repair of orthodontically induced root resorption by ultrasound in humans, Am. J. Orthod. Dentofacial. Orthop. 126 (2) (2004).

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[18] W.T. Ang, C. Scurtescu, W. Hoy, T. El-Bialy, Y.Y. Tsui, J. Chen, Design and implementation of therapeutic ultrasound generating circuit for dental tissue formation and tooth-root healing, IEEE Trans. Biomed. Circ. Syst. 2 (2010) 4961. [19] B.G. Lapatki, O. Paul, Smart brackets for 3D-force-moment measurements in orthodontic research and therapy—developmental status and prospects, J. Orofac. Orthop. 68 (5) (2007) 377396. [20] B.G. Lapatki, J. Bartholomeyczik, P. Ruther, I.E. Jonas, O. Paul, Smart bracket for multi-dimensional force and moment measurement, J. Dent. Res. 86 (1) (2007) 7378.

FURTHER READING Ebrahim et al., 2012A. Ebrahim, J. Yeung, A. Habib, T. EL-Bialy, J.M. AL-Qahtani, Histomorphometric analysis: effect of laser and LED on mandibular growth. Abstract # 954. AADR, Tampa Florida, March 23, 2012. Kumar and Vijayalakshmi, 2006R. Kumar, R. Vijayalakshmi, Nanotechnology in dentistry, Indian J. Dent. Res. 17 (2) (2006) 6265. Rues et al., 2011S. Rues, B. Panchaphongsaphak, P. Gieschke, O. Paul, B.G. Lapatki, An analysis of the measurement principle of smart brackets for 3D force and moment monitoring in orthodontics, J. Biomech. 44 (10) (2011) 18921900. Epub 2011 May 13.