Nanobiomaterials in Dentistry: Applications of Nanobiomaterials

Turkey

Preface of the series

Ecaterina Andronescu, Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Bucharest, Romania

The era of nanosized materials is now considered the center of the evolution of future tools and emerging technologies with wide applications in industry, research, health, and beyond. Despite recent scientific progress, biological applications of nanomaterials are far from being depleted and current knowledge is limited not only by the poor access to significant data, but also by widespread and usually unfounded speculation. Although exhaustive, the current literature is difficult to reach and understand because of the specificity and strict focuses of researchers investigating different applications of nanomaterials.

In this context, the scientific series entitled Applications of Nanobiomaterials was motivated by the desire of the Editor, Alexandru Mihai Grumezescu, and others to bring together comprehensive, up-to-date, and relevant findings on the field of biological applications of nanostructures materials, to promote the knowledge and expand our vision regarding future perspectives. Even though the approached domain is quite specific and research-oriented, this multivolume set is easily intelligible for a wide audience including undergraduate and postgraduate students, engineers, researchers, academic staff, pharmaceutical companies, biomedical sector, and industrial biotechnologies. However, some basic knowledge of the field of materials science (nanobiomaterials, pharmaceutical industry, products for medicinal treatments, nanoarchitectonics for delivery of biological active molecules and release, bone implants, and stomatology) and engineering is a requisite for understanding technical aspects.

The selected authors of each chapter are outstanding specialists in the field of nanobiomaterials, who have made impressive contributions in a specific area of research or applied area within the scope of this book.

Each of the 11 volumes of the series contains 15 chapters, addressing the most relevant and recent matters on the field of the volume.

The first volume, Fabrication and Self-Assembly of Nanobiomaterials, introduces the reader to the amazing field of nanostructured materials and offers interesting information regarding the fabrication and assembly of these nanosized structures. In Volume II, entitled Engineering of Nanobiomaterials, readers can easily find the most commonly investigated methods and approaches for obtaining tailored nanomaterials for a particular application, especially those with a great deal of significance in the biomedical field. In the following step, readers will discover the importance and the ways of modifying the surface of nanostructured materials to obtain bioactive materials, by reading Volume III, Surface Chemistry of Nanobiomaterials. Starting with Volume IV, Nanobiomaterials in Hard Tissue Engineering, and Volume V Nanobiomaterials in Soft Tissue Engineering, the biomedical applications of engineered nanaomaterials are revealed and discussed, focusing on one of the most impacted fields—tissue engineering. Volume VI, Nanobiomaterials in Antimicrobial Therapy, highlights the potential of different nanostructured materials to be utilized in the development of novel efficient antimicrobial approaches to fight the global crisis of antibiotic inefficiency and emerging infectious diseases caused by resistant pathogens. Volume VII moves on to another key biomedical domain—cancer therapy. This volume, Nanobiomaterials in Cancer Therapy, describes current issues of cancer therapy and discusses the most relevant findings regarding the impact of nanobiomaterials in cancer management. Medical Imaging represents the focus of Volume VIII, while Volume IX deals with applications of Nanobiomaterials in Drug Delivery. Volume X, entitled Nanobiomaterials in Galenic Formulations and Cosmetics, refers to the perspectives highlighted by the utilization of nanosized functional biomaterials in the development of improved drugs and active principles for different biomedical industries. Finally, Volume XI is dedicated to the impact of Nanobiomaterials in Dentistry, which currently represents one of the most investigated and controversial domains related to the biomedical applications of nanostructured materials.

Due to their specific organization, each volume can be treated individually or as a part of this comprehensive series, which aims to bring a significant contribution to the field of research and biomedical applications of nanosized engineered materials.

Preface

Alexandru Mihai Grumezescu, http://grumezescu.com/,

Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Bucharest, Romania, Department of Biomaterials and Medical Devices, Faculty of Medical Engineering, University Politehnica of Bucharest, Bucharest, Romania

About the Series (Volumes I–XI)

The increased fabrication of nanosized materials, with applications on the biomedical field by using biomimetic and bioinspired processes and formulations, has recently led to a new concept, named nanobiotechnology. This complex research brings together significant knowledge from physical, chemical, biological, and technological sciences in an applicative field.

Medical applications of nanobiomaterials range from the development of adequate scaffolds for tissue engineering to therapeutic nanostructures, such as targeted drug-delivery systems. The purpose of this multivolume set entitled Applications of Nanobiomaterials is to offer a broad, updated, and interdisciplinary point of view regarding the application of these materials of the future medicine, starting with their fabrication, specific engineering, and characterization but also discussing about their impact in tissue engineering, antimicrobial and cancer therapies, and the development of different medical and cosmetic use products. These books bring together the work of outstanding contributors who have significantly enhanced the basic knowledge and applicative concepts of this research field in their respective disciplines.

The multivolume set Applications of Nanobiomaterials contains 165 chapters, organized in 11 volumes, which are ready to present a novel and up-to-date approach related to this intriguing domain. Each chapter has been carefully composed and illustrated to highlight the relevance of nanobiomaterials on most biomedical fields, revealing the most recent applications on a specific domain. The whole set represents a great material for the academic community, starting with undergraduate and postgraduate students, researchers, engineers, and medical doctors, but also pharmaceutical companies and innovative biotechnologies.

These 11 volumes cover all relevant aspects related to the Applications of Nanobiomaterials as it follows:

Volume I: Fabrication and Self-Assembly of Nanobiomaterials

Volume II: Engineering of Nanobiomaterials

Volume III: Surface Chemistry of Nanobiomaterials

Volume IV: Nanobiomaterials in Hard Tissue Engineering

Volume V: Nanobiomaterials in Soft Tissue Engineering

Volume VI: Nanobiomaterials in Antimicrobial Therapy

Volume VII: Nanobiomaterials in Cancer Therapy

Volume VIII: Nanobiomaterials in Medical Imaging

Volume IX: Nanobiomaterials in Drug Delivery

Volume X: Nanobiomaterials in Galenic Formulations and Cosmetics

Volume XI: Nanobiomaterials in Dentistry

About Volume XI

Volume XI, entitled Nanobiomaterials in Dentistry, brings comprehensive and recent information to this new field, discussing (1) modern nanotechnology used in the production of dental materials; (2) composite resins and adhesives, (bio)cements and dental liners, modified with nanoparticles for enhanced mechanical, antibacterial, and remineralizing properties; (3) nanorestoration of tooth structure, processes that mimic nature and repair oral tissues; (4) role of nanobiomaterials and their diagnostic, therapeutic, and preventive potential in periodontics and implants dentistry; and (5) scientometric overview regarding the recent progress of nanobiomaterials in dentistry.

Volume XI contains 15 chapters, prepared by outstanding international researchers from Brazil, Mexico, Argentina, United States of America, Spain, Italy, Greece, Serbia, Romania, Turkey, Iran, India, Malaysia, Republic of Korea, and Japan.

In Chapter 1, Nanobiomaterials in Dentistry, Rastelli et al. give an overview regarding modern nanotechnology used in the production of a variety of dental materials such as light-cured composite resins, adhesive systems, impression materials, ceramics, dental implant coatings, and bioceramics, among others.

Dolete et al., in Chapter 2, entitled Understanding Dental Implants, introduce an up-to-date review regarding the quality of materials used for the fabrication of dental implants, the dental implant-associated infections, and ways of optimization to decrease infectious risks.

Chapter 3, Effect of Titanium Dioxide Nanoparticle on Proliferation, Drug-Sensitivity, Inflammation, and Metabolomic Profiling of Human Oral Cells, by Garcia-Contreras et al., shows that titanium dioxide nanoparticles (TiO2 NPs) improve mechanical and antibacterial properties of conventional glass ionomer cements (GIC) and also discusses how TiO2 NPs affect the viability, inflammation, and drug-sensitivity in human malignant and nonmalignant cells derived from the oral cavity.

In Chapter 4, Biocements with Potential Endodontic Use, Voicu et al. present an up-to-date overview of the sol-gel synthesis (Pechini method) of 2CaO·SiO2 and 3CaO·Al2O3, main components of WMTA, as well as of WMTA and partially stabilized cements (PSCs).

Kerezoudi et al., in Chapter 5, entitled Nanobiomaterials in Restorative Dentistry, present an overview of the recent applications of nanotechnology in the field of restorative dental materials. Composite resins and adhesives, cements, and dental liners, modified with nanoparticles for enhanced mechanical, antibacterial, and remineralizing properties are discussed.

In Chapter 6, New Trends, Challenges, and Opportunities in the Use of Nanotechnology in Restorative Dentistry, Huerta et al. outline the most promising technology for the nanorestoration of tooth structure, as well as the study and use of processes that mimic nature and repair oral tissues.

Chapter 7, Antimicrobial Effect of Nanoparticles in Endodontics, Kandaswamy et al. describes the applications of antimicrobial nanoparticles in the field of endodontics and their action against key microbial pathogens.

In Chapter 8, Nanotechnology in Dentistry, Ficai et al. introduce recent insights and benefits of nanotechnology in order to revolutionize dentistry as a whole and to introduce significant benefits to the society by improving health by presenting better usage of natural resources.

Chapter 9, Role of Nanomaterials in Clinical Dentistry, by Krishnamurthy and Vijayasarathy, reveals the impact of functional nanoparticles combined in dental restorative materials to serve as valuable strategies in various areas, such as management of dental caries, dentin hypersensitivity, antimicrobial agents, tooth remineralizing mechanisms, and tissue engineering.

Chapter 10, Use of Nanotechnology for the Superlubrication of Orthodontic Wires, by Gracco et al., reveals the recent advances in the improvements of the characteristics and behaviors of orthodontic arch wires with the use of inorganic fullerene-like nanoparticles.

Marković et al., in Chapter 11, Nanosynthesized Calcium-Silicate-Based Biomaterials in Endodontic Treatment of Young Permanent Teeth, describe the recent applications of calcium-silicate-based materials used in endodontic and oral-surgical procedures. The advantages of calcium-silicate-based materials are good apical sealing, setting in the presence of moisture, and acquiring high pH after mixing. Materials based on nanostructured calcium silicates may represent effective therapeutic agents for root canal obturation, especially in the case of immature roots.

Chapter 12, Characterization and Antifungal Activity of the Modified PMMA Denture Base Acrylic: Nanocomposites Impregnated with Gold, Platinum, and Silver Nanoparticles, by Ki Young Nam et al., discusses the synthesis of nanocomposites with proper thermomechanical characters and with significant antiadherent effect against Candida albicans. This chapter deals with the novel dental nanocomposites, the modified Poly(methyl methacrylate) denture acrylic impregnated with noble metal nanoparticles, as an antifungal denture base that can be specified for clinical situations.

Keceli et al., in Chapter 13, Tissue Engineering Applications and Nanobiomaterials in Periodontology and Implant Dentistry, give information about the role of nanobiomaterials and their impact in diagnosis, therapy, and prophylaxis in periodontics and implants dentistry, with particular emphasis given to current challenges and future possibilities related to the strategies of tissue engineering in periodontology and implant dentistry.

Khoroushi et al., in Chapter 14, Nanobiomaterials in Endodontics, provide a critical update regarding the current knowledge and research findings as well as potential future applications of nanobiomaterials in endodontics.

Finally, in Chapter 15, Scientometric Overview Regarding the Nanobiomaterials in Dentistry, prepared by Konur, reviews the research in dentistry and nanomaterials as well as dental nanobiomaterials. The author highlights the major research areas such as dental nanobiomaterials in teeth, dentin, and enamel as well as dental nano-osteoblasts and dental nanoimplants. The research in dental nanobiomaterials has strong public policy implications, providing strong incentives for the key stakeholders involved in dental nanobiomaterial research.

Chapter 1

Nanobiomaterials in dentistry

Alessandra Nara de Souza Rastelli¹, Emanuelle Teixeira Carreira¹, Hércules Bezerra Dias¹ and Michel R. Hamblin²,    ¹Department of Restorative Dentistry, Araraquara School of Dentistry, University of Sao Paulo State-UNESP, Araraquara, Sao Paulo, Brazil,    ²Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, MA, USA

Abstract

During the last decade, nanotechnology has emerged as a separate field of research, mainly because of its application in different areas, such as engineering, medicine, dentistry, and in the development of different technologies used for different purposes. Particularly in dentistry, nanotechnology has shown to be a promising area due to the variety of new treatment options and possibilities. In dental materials, for example, the main applications of nanotechnology have been to achieve better mechanical properties, higher abrasion resistance, less shrinkage, improved optical and esthetic properties, and to provide antimicrobial properties. Antimicrobial activity is a very important property for nanomaterials used in dentistry because of the lack of this property in resin-based materials. Modern nanotechnology is used in the production of a variety of dental materials such as light-cured composite resins, adhesive systems, impression materials, ceramics, dental implant coatings, and bioceramics, among others. Therefore, the purpose of this chapter is to present an overview of nanobiomaterials used in dentistry.

Keywords

Nanotechnology; dentistry; nanomaterial; dental composite resins; biofilm; dental materials

1.1 Introduction

Richard Feynman, in 1959, won a Nobel Prize introducing the science and concept of nanotechnology (Freitas, 2000). Since then, nanotechnology has been employed in many applications, including dentistry, where it plays an important role in diagnosis, dental materials, and different therapeutic techniques. This concept applied in dentistry has a variety of names (West and Halas, 2000).

Firstly, in order to define nanotechnology, it is necessary to understand what a nanometer is. One nanometer (nm) has been defined as a unit that equals one-billionth of a meter.

In this way, different structures can be compared in order to show how small a nanometer is compared to other structures. For example, just one strand of hair has a thickness of 100,000 nm. Then, it is so easy to visualize what is meant by one nanometer and to understand its significance (Gumusderelioglu et al., 2007).

As the size of a nanostructure is around 1–100 nm and the size of atoms is approximately 0.1 nm, it can be clearly seen that nanotechnology works at the level of atoms and molecules. In this way, according to the definition of the National Nanotechnology Initiative, nanotechnology is the manipulation of different materials for different purposes at the nanoscale (Kong et al., 2000). The ability to arrange atoms as we desire and subsequently to achieve effective, complete control of the structure of matter is possible through nanotechnology (Mansoori, 2005; Rieth, 2003; Lakshmisree, Balasubramanian and Deepa, 2013).

According to Ozbay (2006), the purposes of nanotechnology are to enable the analysis of structures using the nanoscale, to better understand the physical properties of structures at nanosize, to manufacture nanostructures, to develop different devices under nanoprecision, and to establish a link between nano- and macroscopic dimensions by appropriate methods.

Mainly because of the small size of nanoparticles and their unique characteristics, they enable defining of many physical events (Poole and Owens, 2003).

Nanotechnology can be defined as the study of the very small materials or structures (Duke, 2003). However, in order to create small structures, nanotechnology involves the development of new materials, devices, and systems with physical, chemical, and biological properties that are different from those of large-scale structures (Kong et al., 2006). Nanotechnology is therefore a promising molecular-level technology with a plethora of applications in scientific, industrial, and medical arenas (Kasraei et al., 2014).

1.2 Nanomedicine

Nanomedicine can overcome many important medical problems. Advances in medical nanotechnology have resulted in a new field called nanomedicine (Freitas, 2000). Robert A. Freitas Jr. first described this concept in 1993, and it was defined as observing, controlling, and treating the biological systems of the human body at the molecular level using nanostructures and nanodevices (Freitas, 2008).

Several applications can be included in nanomedicine. They can range from controlled drug release to tissue scaffolds based on nanoscale design patterns that encourage cell growth and tissue formation, even nanorobots for diagnostic and therapeutic meanings (Freitas, 2005a,b).

Drug molecules can be transported through the body by the circulatory system, however, could cause undesirable effects in untargeted organs. On the other hand, nanorobots can recognize unhealthy cells and can find and destroy them wherever they are located. The drug-delivery systems used to reach the exact target tissue have shown particular importance in cancer treatment in destroying all of the cancer cells and at the same time avoiding harming healthy cells (Freitas, 2005a,b).

Materials and devices based on nanotechnology are described. Some are currently manufactured. Several studies that have been performed in this field are very close to translation into practice; therefore, it can be said that these successful developments are inevitable. Nanomedicine can provide improvements for different techniques in addition to developing new techniques (Freitas, 2005a,b; Caruthers et al., 2007).

1.3 Nanobiomaterials Used in Dentistry

Similar to nanomedicine, nanotechnology applied to dentistry is expected to allow nearly perfect oral health by the use of nanomaterials and biotechnologies, including tissue engineering and different technologies such as nanorobots (Freitas, 2000).

1.3.1 Photoactivated Restorative Nanomaterials Used in Dentistry

Composite resins are polymeric materials composed by three principal components. Two of them are based on organic and inorganic matrix, and the another is based on an organosilane or coupling agent to bond the inorganic matrix represented by fillers to the organic resin. The organosilane could be defined as a molecule containing silane at one end (forming an ionic bond to SiO2) and methacrylate groups at the other end (forming a covalent bond with the resin) (Goldstein, 2002).

The organic matrix of composite resins is mainly made up of mono-, di-, or trifunctional monomers. Additionally, a free radical polymerization initiation system in photoactivated composite resins is based on camphoroquinone used with a tertiary aliphatic amine-reducing agent (4-N,N-dimethylamino-phenyl-ethanol, DMAPE). For composite resin systems chemically activated, a peroxy-compound radical-initiator, benzoyl peroxide, is used with an aromatic tertiary amine (N,N-dihydroxyethyl-p-toluidine) and an acceleration system (dimethylaminoethyl methacrylate or DMAEM, ethyl-4-dimethylaminobenzoate or EDMAB, or N,N-cyanoethyl-methylaniline or CEMA), which acts in concert with the initiator, allowing curing to take place in a clinically acceptable timescale. One stabilizer or inhibitor agent, such as hydroquinone monomethyl ether, is always used to improve the lifetime storage prior to curing and its chemical stability. Also, 2-hydroxy-4-methoxybenzophenone, a photo-protective compound, that absorbs ultraviolet (UV) light below 350 nm is used to provide color stability and avoid the effects of UV light on the amine compounds in the initiator system that can provide discoloration in the medium to long term (De la Macorra, 1999).

Bisphenol A glycidyl methacrylate (Bis-GMA) is the most frequently used monomer in dental composite resins. Whether alone or in combination with urethane dimethacrylate (UDMA), it constitutes around 20% (v/v) of standard compositions. In general, it is accepted that monomer or monomer combinations with lower molecular weight show a greater percentage of shrinkage. Because this material is highly viscous, in order to facilitate the manufacturing process and clinical handling it is diluted using other low-viscosity monomers with low molecular weight, such as bisphenol A dimethacrylate (Bis-DMA), ethylene glycol dimethacrylate (EGDMA), triethylene glycol dimethacrylate (TEGDMA), methyl methacrylate (MMA), or UDMA (Holter et al., 1997; Culbertson et al., 1997).

The polymerization process of the composite resins involves a great or low degree of shrinkage, depending on the organic matrix. To reduce or avoid this negative effect, dental manufacturers have tested different monomers, including spiro-ortho-carbonates, which expand (Millich et al., 1998), epoxy-polyol system combinations, which show 40–50% less shrinkage in vitro C bonds. Ormocers, defined as modified composites with organic and inorganic fillers, have also shown the ability to reduce curing shrinkage, albeit minimally (Manhart et al., 2000). However, the main dental composite resin manufacturers still concentrate on the traditional systems, mostly adding a Bis-GMA/TEGDMA monomer or a Bis-GMA/UEDMA/TEGDMA combination to produce the organic matrix.

Different classifications have been used for composite resins. The main classification is based on their composition. The main purpose of the classification of composite resins is to make it easier for the surgeon dentists to identify and use them in different clinical cases. One of the most popular classification is that of Lutz and Phillips, which is based on the filler size of inorganic particles. These authors divided composite resins into macrofiller composites (particles from 0.1 to 100 μm), microfiller composites (0.04 μm particles), and hybrid composites (fillers of different sizes) (Lutz and Phillips, 1983).

However, later a new and more detailed classification by Willems et al. (1992) based on a number of different parameters such as Young’s modulus, the percentage (by volume) of inorganic filler, the size of the main particles, surface roughness, and compressive stress (listed in Table 1.1) was introduced.

Table 1.1

Composite Types and Fillers Used (Willems et al., 1992)

More recently, a few years ago, a new type of composite resin based on nanotechnology was developed, and in this way a new classification of composite resins was proposed, as shown in Table 1.2.

Table 1.2

Filler Sizes and Composition of Composite Resin Materials (New Classification)

Nanocomposites are claimed to combine the good mechanical strength of the hybrids (Moszner and Salz, 2001; Moszner and Klapdohr, 2004) together with the superior polish of the microfills (Turssi, et al., 2000). Other positive features that have been reported are high wear resistance (Yap et al., 2004; Turssi et al., 2005), improved optical characteristics, and reduced polymerization shrinkage (Moszner and Salz, 2001; Chen et al., 2006). Also, these materials are available as various nanohybrid types containing milled glass fillers and discrete nanoparticles (40–50 nm) and as nanofill types, containing both nanosized filler particles, called nanomers and agglomerations of these particles (Mitra et al., 2003). The agglomerations of these particles can provide a distinct mechanical reinforcement compared with the microfill or nanohybrid systems resulting in significant improvements to their strength and durability (Curtis et al., 2009).

In composite resin technology, the particle size and quantity are crucial when determining how to best utilize the restorative materials. Changes of the filler component remain the most significant development in the evolution of composite resins (Roulet, 1987), because the filler particle size, distribution, and the quantity that can be incorporated dramatically influence the mechanical properties and clinical success of the composite. In general, the mechanical and physical properties of composites improve in proportion to the amount of filler added. Many of the mechanical properties depend on this filler phase, including compression strength and/or hardness, flexural strength, elastic modulus, coefficient of thermal expansion, water absorption, and wear resistance. Nanotechnology may be responsible for the production of composite resins with filler particles smaller than usual, higher concentrations can be included, and are polymerized into the resin system with molecules designed to be compatible when coupled with a polymer, to provide special and better characteristics (physical, mechanical, and optical) (Leinfelder, 1989) than others.

Nanofilled composite resins provide a better finish on the surface. This characteristic could improve surface texture, and material biodegrading over time in this way, may be reduced. These composite resins have also achieved good mechanical properties, indicating possible use in the anterior and posterior teeth. Also, the lower size of the particles leads to less curing shrinkage, creates less cusp wall deflection, and reduces the presence of microfissures in the enamel edges, which are responsible for marginal leakage, color changes, bacterial penetration, and possible postoperative sensitivity (Meyer et al., 2003). The main drawback of nanoparticles is that since the particles are so small, they do not reflect light, so they are combined with larger-sized particles, with an average diameter within visible light wavelengths (i.e., around or below 1 μm), to improve their optical properties.

In addition, the adhesion of restorative biomaterials to the mineralized hard tissues of the tooth should be optimized to provide the best mechanical strength, marginal adaptation, and seal, while improving the reliability and longevity of the adhesive restoration. The particle sizes of conventional composites are different to the structural sizes of the natural components of the tooth, such as hydroxyapatite (HA) crystals, dentinal tubules, and enamel rods, so that there is a potential for mismatch that compromises adhesion between the particles (40 to 0.7 nm) in the restorative material and the nanoscopic particles (1–10 nm) in the tooth structure. Nanocomposite systems have the potential to improve this match between the tooth structure and the nanosized filler particles and provide a more stable and natural interface between the mineralized hard tissues of the tooth and these advanced restorative biomaterials.

1.3.2 Nanosolutions

Nanosolutions can provide particles based on nanotechnology, which can be added to different solvents and polymers being dispersed homogeneously. In this way, nanotechnology applied to bonding agents ensures homogeneity and that the adhesive can be perfectly mixed (Kim et al., 2005). These parameters, among others, are important to obtain an adequate adhesion to dental structures.

1.3.3 Esthetic Materials

In combining finishing and polishing techniques used in dentistry, a liquid polish or paste application based on nanotechnology might provide a glossier surface for composite resin restorations.

1.3.4 Nano-Optimized Moldable Ceramics

In order to optimize moldable ceramics, some materials based on nanotechnology can be used. In this way, nanofillers, nanopigments, and nanomodifiers could be used in order to enhance finishing and polishing ability and reduce wear, adjust the color of the fillings to the remaining teeth, and increase the stability of the material and prevent sticking to instruments (Schirrmeister and Huber, 2006).

1.3.5 Impression Materials

Nanofillers can be integrated into vinylpolysiloxanes, in order to produce a unique addition of siloxane impression materials. Some properties, such as better flow, hydrophilic characteristics, and enhanced detail precision could be improved (Jhaveri and Balaji, 2005). These characteristics are very important to impression materials used in dentistry.

1.3.6 Nanoencapsulation

Some systems have been developed as targeted release systems that could include new vaccines, antibiotics, and drug-delivery systems with reduced side effects. Specialized nanoparticles could be engineered to target different oral tissues (Saravana Kumar and Vijayalakshmi, 2006).

1.3.7 Other Products Manufactured

Other products based on nanotechnology could be produced for different uses, such as

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

b. Medical dressings for improved wound healing;

• Biodegradable nanofiber delivery platform for hemostatics;

• Wound dressings with silk nanofibers currently in development;

• Nanocrystalline silver (Ag) particles with antimicrobial properties on wound dressings (Acticoat™, UK) (Saravana Kumar and Vijayalakshmi, 2006).

Ag has been shown as an antimicrobial material, targeting a broad spectrum of Gram-positive and Gram-negative bacteria and even vancomycin-resistant strains. Ag nanoparticles show greater surface ratio by providing greater solubility, chemical reactivity, and higher antibacterial activity compared to conventional, Ag particles (Zheng et al., 2010).

c. Bone-targeting nanocarriers (Kanaparthy and Kanaparthy, 2011).

Biomaterials based on calcium phosphate can be described as an easily flowable, moldable paste that conforms to and interdigitates with host bone, supporting growth of cartilage and bone cells.

1.3.8 Materials to Induce Bone Growth

Possible applications of nanotechnology for tissue engineering and stem cells in dentistry include the treatment of orofacial fractures, bone augmentation, cartilage regeneration in the temporomandibular joint, pulp repair, periodontal ligament regeneration, and implant osseointegration. Tissue engineering can provide the placement of implants, eliminating a prolonged recovery period, and being biologically and physiologically more stable than previously employed implants, and it can safely support early application of mechanical loads (Stephen, 2005; Roberson et al., 2006).

Bone is composed mainly of organic compounds (collagen) reinforced with inorganic ions, that is, HA. These characteristics are required to simulate the nanostructure for dental applications. The smaller particle size gives a larger surface area. Materials based on nanotechnology used to mimic bone tissue show a microstructure combining nanopores situated between the crystallites. This material structure is completed by pores under the micrometer scale. Under this process, a rough surface area is formed at the boundary layer between the biomaterial and the cells. This characteristic is very important for good cell adhesion and fast cell growth. All pores are self-interconnecting. Because the cells are too big for the small pores, blood plasma containing many important proteins is retained in the interstices (Kanaparthy and Kanaparthy, 2011).

Some examples of HA nanoparticles used to treat bone defects are:

• Ostium (Osartis GmbH, Germany) HA;

• VITOSSO (Orthovita, Inc, USA) HA + TCP;

• NanOSSTM (Angstrom Medica, USA) HA.

Fibers based on nanotechnology can show similarity in shape to the arrangement between collagen fibrils and HA crystals in bone structure. Some studies performed during recent years suggest that nanoparticles can be used to improve the mechanical properties of these materials. As the nanoparticles show a size comparable to that of the cellular and macromolecular components, they have been described as a preferred material (Gumusderelioglu et al., 2007; Ashammakhi et al., 2007). Bone replacement materials developed through nanotechnology are commercially available (Saravana Kumar and Vijayalakshmi, 2006; Strietzel et al., 2007; Wagner et al., 2006).

Nanocrystalline HA could provide bone grafts with better characteristics. Additionally, it has been shown that nanocrystalline HA could stimulate in a better way the cell proliferation required for periodontal tissue regeneration (Kasaj et al., 2008).

Nanobioactive glasses have shown biocompatibility with gingival fibroblasts using an in vitro model (Tavakoli et al., 2012). Some bioactive glasses have been used to fill small voids, such as those found during postextraction sockets and periodontal bone defects, and as an adjunct to the longer-lasting bone-grafting materials.

1.3.9 Nanoneedles

Needles used to suture have incorporated nanosized stainless steel crystals in their structure. The trade name of this structure is Sandvik Bioline, RK 91TM needles (AB Sandvik, Sweden). Nanoscale tweezers have been also developed which may make individual cell surgery possible in the foreseeable future (Saravana Kumar and Vijayalakshmi, 2006).

1.3.10 Self-Assembly

Self-assembly is an autonomous and spontaneous organization of different components into patterns or structures without human intervention. Polyelectrolyte materials bearing a number of charged groups are most commonly used in self-assembly as they enable stable, smooth, homogeneous films to be formed with a number of different functional groups. Of these, the best-studied systems are polyallylamine with polystyrene sulfonate and diazo-resin with polystyrene sulfonate (Kong et al., 2006; Bartold et al., 2000). Recently, the use of pH-induced self-assembly of a peptide-amphiphile has been used to artificially construct a nanostructured fibrous scaffold with the structural features of biological extracellular matrix. Additionally, after crosslinking, the newly produced fibers are able to direct mineralization of HA to form a composite material in which the crystallographic axes of HA are aligned with the long axes of the fibers which mimic the periodontium.

1.3.11 Nanomaterials for Periodontal Drug Delivery

Nanomaterials widely explored for controlled drug release include hollow spheres, core-shell structure, nanotubes, and nanocomposites. Polymers or microparticle-based hydrogels have been applied in dentistry and periodontics in particular in recent years. These delivery vehicles can affect the rate of drug release because of their structure, but the development of more refined means of delivering medications at therapeutic levels to specific sites is an important clinical issue (Levy, 1986; Page, 1984).

Into nanospheres based on a biodegradable polymer, drugs could be incorporated, and this allows for timed release of the drug as the nanospheres degrade, thus facilitating site-specific controlled drug delivery.

Nanocomposite hydrogels have been synthesized as model systems for in situ implanted local drug-delivery devices for the treatment of periodontal infections. The composite material includes the following components: nanoparticles, a matrix gel, and a suitable antibacterial drug. The nanoparticles were obtained by free-radical-initiated copolymerization of monomers, 2-hydroxy methymethacrylate and polyethylene glycol dimethacrylate in aqueous solution. The same monomers were used to prepare crosslinked matrices by photopolymerization. Nanocomposite hydrogels were obtained by mixing nanoparticles, monomers, and the drug in aqueous solution, and were then crosslinked by photopolymerization. These nanoparticles were suitable for incorporation into a hydrogel matrix and could be used to design new drug-delivery devices for dental and periodontal application (Jayakaran and Arjunkumar, 2013). We list below some advantages of nanocomposite systems for periodontal drug delivery (Goodson et al., 1983):

• Highly dispersible in aqueous medium;

• Uniform distribution of the active agent over an extended period of time;

• Controlled release of the drug;

• Reduced frequency of administration;

• Increased stability;

• Can penetrate regions inaccessible to other delivery systems.

Recently triclosan-loaded nanoparticles prepared using poly (D,L-lactide-coglycolide), poly(D,L-lactide), and cellulose acetate phthalate showed effective results in promoting a reduction in inflammation (Kohli and Martin, 2003; Piñón-Segundo et al., 2005). Microspheres containing tetracycline are commercially available as Arestin for drug delivery inside periodontal pockets (Kong et al., 2006). According to Botelho et al. (2010), a doxycycline gel based on nanostructure was shown to preserve the periodontal surface following experimental periodontal disease in rats.

1.3.12 Photodynamic Therapy

Antimicrobial photodynamic therapy (aPDT) has been defined as a treatment for the removal or control of infections by applying a photosensitizer or dye associated with a light source of a specific wavelength, for example, toluidine blue excited with a wavelength of about 630 nm. Recently, methylene blue (a phenothiazinium photosensitizer) has been encapsulated within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (≈150–200 nm in diameter) and was shown to offer a novel design of nanoplatform for enhanced drug delivery and photodestruction of oral biofilms. Indocyanine green-loaded nanospheres, classified as a new photosensitizer, irradiated under 805 nm wavelength with a low-level diode laser showed an aPDT-like effect, which might potentially be useful for aPDT in dentistry (Nagahara et al., 2013).

1.3.13 Implants

Nanotechnology is increasingly being used for surface modification of dental implants, because the surface properties play an important role in maintaining their long-term stability in bone tissue. It is necessary for direct contact between bone and implant in order to promote a good biomechanical anchoring, rather than encapsulation of the implant by fibrous tissue (Catledge, 2002).

The natural bone surface has a roughness of approximately 100 nm, and such nanoscale details are therefore important on the surfaces of implants. Osteoblast proliferation has been induced through the creation of nanosized particles on the implant surface (Gumusderelioglu et al., 2007; Tetè et al., 2008). Roughening the implant surface at the nanoscale level is important for the optimum cellular response that occurs in the tissue and encourages integration of the implant into the bone (Braceras et al., 2009; Ellingsen et al., 2006).

Titanium implants treated with a calcium surface coat based on nanotechnology have been inserted into rabbit tibias, and their effect on osteogenesis has been evaluated. The nanostructured calcium coat increased the responsiveness of the bone around the implant (Suh et al., 2007). In vitro studies have shown that the topography of the implant surface has a large effect on osteogenic cells, and that the nanosized surface morphology enhances the adhesion of osteoblastic cells. Furthermore, the morphology of nanosized surface enhances the surface area and thus provides an increased implant surface area that can better react to the biologic environment (Suh et al., 2007; Meirelles et al., 2008; Chiang et al., 2009; Park et al., 2009).

Recently three different nanostructured implant coatings have been developed:

1. Nanostructured diamond: This kind of coating shows very high hardness, improved toughness over conventional microcrystalline diamond, low friction, and good adhesion to titanium alloys (Colon et al., 2006).

2. Nanostructured processing of HA coatings: This coating material is used to provide the desired mechanical characteristics and enhanced surface reactivity and has been shown to increase osteoblast adhesion, proliferation, and mineralization (Colon et al., 2006).

3. Nanostructured metalloceramic coatings: These coatings provide continuous variation from a nanocrystalline metallic bond at the interface to the hard ceramic bond on the surface (Colon et al., 2006).

Nanostructured ceramics, carbon fibers, polymers, metals, and composites enhance osteoblast adhesion and calcium/phosphate mineral deposition. Studies have suggested that nanophase ZnO and TiO2 may reduce Staphylococcus epidermidis adhesion and increase the osteoblast functions that are necessary to promote the efficacy of orthopedic implants (Meyer and Bühner, 2006).

1.3.14 Dental Nanorobots

Although medical robots are not anticipated to have an effect on dentistry in the near future, it is not too early to consider their potential effects (Schleyer, 2000). Dental nanorobots should be able to move through teeth and surrounding tissues by using specific navigational and motion capabilities. Nanocomputers that have been previously programmed by acoustic signals used for ultrasonography could control the nanorobotic functions and location (Freitas, 2000). Nanorobots (dentifrobots) could be deposited by mouthwash or toothpaste on the surfaces of teeth providing the removal of organic substances by moving over both the supragingival and subgingival surfaces, preventing the accumulation of biofilm and dental calculus. These nanorobots could move from 1 to 10 μm/s and would be safely deactivated when they were swallowed (Saravana and Vijayalakshmi, 2006).

1.3.15 Nanocomposite Artificial Teeth

Another application of nanotechnology is related to the production of artificial teeth. In these artificial teeth based on nanocomposite, inorganic fillers under nanosize are diffused homogeneously without any accumulation in the matrix. In this way, the smoothness of the surface can be maintained even when the teeth are eroded. Some studies have shown that artificial teeth based on nanotechnology were shown to be more durable than acrylic and microfill composite teeth and showed a higher resistance to abrasion (Suzuki, 2004; Ghazal et al., 2008a,b; Loyaga-Rendon et al., 2007). Additionally, composite resin artificial teeth based on nanosized filler show better color than other systems (Imamura et al., 2008).

1.3.16 Dental Tissues and Nanostructures

Regardless of the fact that dental hard tissues such as enamel, cement, and bone are formed by the organized accumulation of HA crystals with carbon dioxide, enamel tissue presents different characteristics from those, mainly because it does not contain collagen and, in this way, the remodeling is not possible. During enamel mineralization, spontaneous self-assembly of the amelogenin protein in nanospheres plays an important role in controlling the growth of apatite crystals with carbon dioxide. This process can be implemented in order to produce other mineralized tissues, such as bone and cementum, in which nanostructures are similarly involved (Kong et al., 2006).

1.3.17 Digital Dental Imaging

Also, nanotechnology could provide improvements on digital dental imaging. For example, in digital radiography mediated by nanophosphor scintillators, the high-quality images could be obtained using a low radiation dose (Mupparapu, 2006).

1.3.18 Applications of Nanotechnology in Oral and Maxillofacial Surgery

Nanotechnology could provide many benefits, particularly in precise surgery to remove tumor tissue (Troulis et al., 2005).

1.3.19 Nanotechnology for Preventing Dental Caries

Dental caries remains one of the most common and biofilm-dependent oral diseases, and can result in the destruction of tooth structure by acidic attack from cariogenic bacteria, such as Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus spp. These bacteria are frequently present as aggregates of microorganism cells attached to each other, in an extracellular matrix and firmly attached to the tooth surface (i.e., oral biofilm or dental plaque) (Fejerskov and Kidd, 2008; Gross et al., 2012). Caries is a site-specific and dynamic disease involving destruction of the tooth structure, resulting from an imbalance in the physiologic equilibrium between mineral ions present in the tooth structure and dental plaque fluid involving demineralization and remineralization processes (Fejerskov and Kidd, 2008). Reductions in the pH (<5.5) of the oral biofilm due to the presence of bacterial acids can cause the tooth to lose calcium and phosphate ions (from enamel and dentin) causing tooth demineralization. In the remineralization process calcium and phosphate lost by the enamel may be redeposited into the tooth from dental plaque fluid or by direct action of salivary calcium and phosphate soon after the biofilm is removed by tooth-brushing (Cury and Tenuta, 2009).

However, the number of ions regained is lower than the number lost and the net result is a small but steady mineral loss. If biofilm accumulation and/or acid production are not inhibited, enamel mineral loss will continue by repeated events of mineral dissolution (demineralization). This will eventually exceed the capacity of oral fluids to repair mineral loss, and the disease will show its clinical signs—caries or carious lesions (Fontana et al., 2010). These lesions range from white spot lesions (early carious lesions with the appearance of white chalky areas on enamel) to frank cavities in the dentin. Consequently, the control of dental caries is traditionally centered on mechanical or nonspecific control of the dental plaque, because this is the chief causative factor.

Significant progress has been made in reducing and controlling dental caries using fluoride (Fontana et al., 2010). Fluoride can inhibit demineralization and can promote remineralization of hard dental tissues. Nevertheless, the limited penetration of fluoride in dental plaque may restrict its beneficial inhibitory effects in residual plaque deposits that remain in inaccessible sites of stagnation (Watson et al., 2005). Consequently, prevention and management of caries lesions at proximal surfaces (areas where the surface of one tooth touches the surface of another) and around restorations are still challenges for dental caries research (Malterud, 2012).

Secondary caries is defined as positively diagnosed carious lesion occurring at the margins of an existing restoration (McComb et al., 2002).

This phenomenon remains as one of the most frequent reasons leading to a short lifetime of dental fillings (Burke et al., 2001). In this way, it is necessary to replace the restorative materials of the dental fillings (Mjor, 1997). The principal cause of enamel demineralization is related to the adhesion of microorganisms to the teeth and/or to the fillings, which produces pathogenic dental plaque. Therefore, one of the most common methods for preventing enamel demineralization around the restorations is related to the use of dental materials that show resistance to biofilm accumulation (Ahn et al., 2009). On the other hand, as various laboratory and clinical researches have demonstrated, more plaque accumulation occurs on resin composites compared to either other restorative materials or to dental hard tissues, which results in higher prevalence of secondary caries around composite resin restorations (Sevinç and Hanley, 2010).

The amount of biofilm formation on resin composites is related to the surface roughness, which is governed by the resin type, filler size, and percentage of filler. Additionally, the dental composite resins did not show antimicrobial properties or do not have intrinsic components with antimicrobial properties (Sehgal et al., 2007). Therefore, recent studies have paid growing attention to the antibacterial activity of composite resins in order to reduce the risk of recurrent decay around esthetic direct restorative materials. Different approaches have been used to introduce antibacterial activity into resin-based dental composites and