Nanotechnology

The introduction of microfill restoratives in the early 1970s ushered in the era of dental nanotechnology. As discussed in Chapter 13, microfilled composites contain silicon dioxide (SiO₂) reinforcing particles about 40 nm in diameter that are dispersed in prepolymerized resins that have been ground to form so-called organic filler particles in the micron size range. Current microhybrid and nanofilled composites contain filler particles range from about 20 to 600 nm. This use of nanoparticle technology allows the formulation of dental materials with high translucency, excellent initial polish, and retention of gloss while maintaining mechanical properties and wear resistance equivalent to those of current clinically proven hybrid composites. Several 2- to 3-year clinical trials have investigated the nanohybrids performance in a variety of oral restorations and found that the nanohybrids show great promise for extending survival beyond the current 5 to 10 years. Currently, a variety of approaches designed to overcome the deficiencies of nanoparticle composites are in progress. None of these is likely to result in a breakthrough that will lead to a universal esthetic composite that can rival the durability of amalgam. However, there is a high likelihood that many will contribute incremental advantages that, when combined and optimized, will result in such a material by the next decade.

Other recent applications of nanotechnology in dentistry have focused on the delivery of molecules that promote hard tissue remineralization by noninvasive techniques. In this context, the most promising technology for the nanorestoration of tooth structure is biomimetics, the study and use of processes that mimic those that occur in nature, particularly those that involve self-assembly of components to form, replace, or repair oral tissues (Saunders, 2009). These concepts are discussed further later in this chapter.

For dental biomaterials, nanoparticulates have been shown to strongly influence the host response at both cellular and tissue levels, making their use particularly attractive for modifying dental implant surfaces. Electrophoretic, sol-gel and pulsed laser deposition, sputter coating, and ion beam–assisted deposition, among others, are approaches that have been utilized to develop nanotextured thin-film biocompatible coatings for implant surfaces. These technologies reduce the thickness and particle size of the coating layer and thereby increase its specific surface area and reactivity, thus improving the interaction with the surrounding living tissue. See, for example, Bayne (2005) and (Subramani and Ahmed, 2012).

These technologies are at an advanced stage and their use to develop nanosized preparations of various components in dental materials and improve both performance properties and durability in the near future is quite likely. However, it should be noted that nanosized particles and surface features with very high surface area–to-volume ratios are usually different in their bioactivity, solubility, and antimicrobial effects compared with larger particles. Thus, these changes in properties cannot be extrapolated by an inverse linear analysis of particle size, but must be determined through in vitro and in vivo testing of the nanomaterials. Potentially important nanoparticles will range from metals, such as silver, to ceramic powders, such as titanium dioxide. For example, in situ–generated silver nanoparticles have been reported to be highly effective in restorative resins, bonding resins, and prosthetic resins for inhibiting a variety of biofilm-forming bacteria while not interfering with manipulation, curing, mechanical properties, or other performance properties (see Fan et al., 2011, and Oei et al., 2012).

Several of the emerging materials and technologies described later in this chapter rely on nanotechnology.

Resin Restorative Materials

Prolonging the service life of dental restorations is of great public health importance because it delays or avoids the need for repair or replacement of the restorations. The frontier for resin restorative materials continues to be the reduction of composite shrinkage, reduced porosity, improving the composite-dentin interface, reducing wear and attrition, and increasing the degree of conversion of resin monomers. Improvements in these characteristics are needed in order to increase the service life of resin-based restorations and thereby reduce the need to retreat the original restored teeth.

Longevity and survival studies have shown that dental resin composites available during the past 10 years or so have an average replacement time of 5.7 years. The failures were mainly caused by three primary factors: (1) surface loss due to two- and three-body wear; (2) marginal deficiencies due to breakdown and/or gap formation and (3) secondary marginal caries (secondary caries). Whereas the relatively recent innovations discussed earlier (“Innovations in Dental Composites” in Chapter 13) have likely increased the service life of currently marketed resin composites, there is still an incomplete understanding of all factors that lead to failures. For example, there remains significant uncertainty on the interactions among several variables including bacterial biofilms, such as dental plaque and the mechanisms of wear, fatigue, fracture, and secondary caries. Current ongoing research is making progress to gain better insights into how interactions among physical and oral environmental factors and the composition of composites initiate and influence failure mechanisms (Petrovic et al., 2010). Future research should lead to developments that further extend durability and survivability, possibly rivaling that of amalgam.

Another factor that influences longevity is operator error. Materials that present difficult handling, curing, and other technique-related problems are inherently prone to mistakes that often lead to material defects (e.g., air inclusions and low degree of cure), which in turn hasten the onset of fatigue and other failure mechanisms. Here, too, substantial research and development effort is in progress that can be expected to lead to a series of ever more “technique insensitive” (forgiving), operator-friendly, resin-based materials that also maintain a balance of other required properties such as strength, wear resistance, and esthetics.

Two recently introduced novel flowable composites, G-aenial Universal Flo (GC America, Alsip, IL) and Surefil-SDR flow (DENTSPLY International, York, PA), among others, exemplify such operator-friendly materials. Both are highly translucent and offer flowable rheologies (i.e., consistencies) and easy handling together with a large depth and degree of conversion; they are marketed as bulk fill, universal restorative resins with exceptional ease of placement. Both exhibit low shrinkage and low shrinkage stress when tested in vitro, and early clinical trial results show that they have early-stage wear resistance and durability similar to those of current posterior resins.

G-aenial Universal Flo is based on 4,8-di(methacryloxy methylene)-tricyclodecane (TCDDMA), a bulky, space-filling dimethacrylate monomer (see Figure 13-22 in Chapter 13). TCDDMA has a tricyclodecane three-ring central group that prevents monomers from aligning and thus offsets polymerization shrinkage. This “steric hindrance” effect slows the rate of polymerization and lengthens the time needed for the curing reaction to reach the point of solidification. This facilitates the ability of adjacent polymer chain segments to slip among themselves and relax stresses that develop before the resin paste solidifies.

Surefil-SDR flow utilizes what the company describes as a “polymerization modulator” in the backbone of the SDR resin monomer. A schematic of a dimethacrylate monomer—which appears to have a bulky, space-filling central group similar to that of TCDDMA—is shown in the company literature. Whatever the chemical structure, published results show that the material has flow and other handling characteristics, together with a high translucency, that promote a high degree and depth of cure. These features place it in the category of technique insensitive.

These two highly flowable composite products also contain a reinforcement filler loading on a par with highly loaded, nonflowable, even “packable” hybrids such as those described in Chapter 13. This high loading, together with low curing stress and a high level and depth of cure, account in large part for the expectation of their high durability and long service life. At this time the means whereby this combination of high filler loading and a flowable working consistency are achieved have not been disclosed. However, given the intensity of research and development, other products of this type can be expected and, with further improvements, significant progress toward the goal of ensuring reliably placed restorative resins with the durability and forgiveness of amalgam combined with the esthetics of porcelain can be expected in the near future.

Antimicrobial Materials

Although the clinical performance of dental resins has improved remarkably in terms of durability, bond strength, and esthetics, most resins lack antimicrobial properties. Consequently, the inclusion of bacteriostatic or bactericidal properties is greatly needed, especially since synthetic materials of all types readily facilitate bacterial colonization and biofilm formation. Such new, improved materials may be derived from formulas with better nanofiller or improved interphase bonding agents for the ceramic fillers and resins. Future composite restoratives may also arise from (1) new fluoride-containing monomers for the prevention of secondary caries (such as fluoride-releasing dimethacrylate monomer containing a ternary zirconium fluoride chelate), (2) antibacterial monomers (such as methacryloyloxydodecylpyridinium bromide (MDPB), (3) antibacterial and fluoride-releasing monomers, (4) the use of a higher filler percentage with nanoparticles, and (5) matrix metalloproteinase (MMP)–inhibiting components incorporated in the composite. Continual fluoride uptake (recharging from food or periodic treatments) and release are desirable in restoratives to inhibit or prevent caries. Antimicrobial characteristics are desirable, but they must be sustained after polymerization. Silver and titanium particles continue to be considered for antimicrobial effects, alone or attached to polymers. Silica nanoparticles are already used in composites to improve polishability and translucency, but new nanoparticles may exhibit enhanced penetration into etched dentin to improve mechanical and adhesive properties. The MMP-inhibiting materials may deter degradation of the etched dentin that interfaces with a dental composite in the hybrid layer. Suppression of MMP by agents other than ethylenediaminetetraacetatic acid (EDT) and chlorhexidine can also inhibit remineralization, which is a likely area of improvement for dentin bonding agents.

The treatment and management of dental caries have always been fundamental parts of dentistry. Early discovery of the disease’s demineralization process facilitates the ability to inhibit or arrest the caries process or to remineralize the lesion’s tissue, which is of significant value to the patient. New non-fluoride-containing, antimicrobial monomers such as MDPB, may help to prevent secondary caries, whereas other more effective fluoride-containing/releasing resins may be invented for this purpose. Antibiotics are being used as endodontic irrigation rinses, especially when they are combined with various acids or chemicals that quickly dissolve the dentinal smear layer created by endodontic instruments in a root canal. Combination devices containing a drug, BMP, or amino acids are envisioned for endodontic and periodontal uses. Antimicrobial materials are needed for restoratives and other dental materials that have novel and improved properties compared with those that are now available. For instance, future materials may use the antimicrobial properties of the calcium silicates or calcium aluminates for enhanced endodontic and pulpal procedures necessitated by the adverse effects of bacterial action. Silver zeolite, triclosan, and modified (chlorinated) polyethylene or other polymers may satisfy applications where an antimicrobial material is needed.

Preventing and removing biofilms is especially important for periodontics and endodontics. Adjunctive liquids are needed that can quickly kill and remove bacterial colonies in biofilms during periodontal scaling. In endodontics, new irrigants are needed to better remove and deactivate smear layers containing remnant bacteria after root canal preparation. As with acid etching, the frontier for smear layer removal or biofilm dissolution continues to advance with faster, more effective treatment regimens.

Remineralizing Agents and Materials

The remineralization of tooth surfaces with incipient lesions, prevention of secondary caries, and durable bonding to etched dentin are key areas of research for future dental materials (Donly et al., 1994 and Lippert et al., 2004) because of their great public health importance in preventing sustained enamel demineralization and prolonging the service life of composite restorations without repair or replacement. In the future, nanoparticles of hydroxyapatite may be helpful for remineralization because they are on the same crystalline scale as naturally occurring hydroxyapatite crystals in teeth. A promising example of this approach was reported by (Li et al., 2008) who found that 20-nm nanohydroxyapatite particles provided an anticaries repair effect while larger hydroxyapatite particles did not.

New remineralizing dentin bonding agents should ensure wetting and flow and preferably completely fill the demineralized zone created by etching prior to or simultaneous with bonding to the restorative material. For instance, new MTA-type* products have been tested in the lab with polyacrylic acid and sodium tripolyphosphate as a dentin-bonding layer. When it was applied under a restorative material, the combined material infiltrated the demineralized collagen fibrils with precursors that restored the calcium phosphate at the interfaces of the dentin and the restorative material. These and other remineralizing materials are needed to move forward from the laboratory to clinical trials of new dental adhesives for composites. Incorporation of some of these technologies into primers and dentin bonding agents are expected to both inhibit caries activity and increase the service life of composite restorations.

Low concentrations of fluoride are known to promote enamel and dentin remineralization (Gelhard and Arends, 1985). However, after treatments with topical fluoride gels, rinses, or dentifrices, salivary fluoride concentrations decrease exponentially to low concentrations within a few hours.

The appearance of secondary (recurrent) caries denotes a state of demineralization of the tooth tissues at the margin of a restoration. In today’s dental practices, the margins of restorations are often placed in subgingival areas for the sake of enhanced esthetics, but this situation predisposes to increased plaque retention and secondary caries.

The clinical diagnosis of secondary caries is the most common reason for the replacement of restorations in general practice; this includes all types of restorations, such as those produced with amalgam, composite, and glass ionomer cement. Typically 50% to 60% of all replacements of directly placed restorations in general practice are associated with the diagnosis of secondary caries. Since 50% to 75% of all restorations in adults are replacements of previously inserted restorations, the clinical diagnosis of secondary caries leads to billions of dollars of costs for patients. Therefore, it is important, in this context, to assess the scientific basis for the clinical diagnosis and prevention of secondary caries and to enhance the potential to remineralize previously demineralized enamel adjacent to restorations.

The dental literature reflects a strong demand for preventive and “healing” therapies for individuals at moderate risk for caries to prevent a shift to a high level of risk. For some of these individuals, the daily ingestion of fluoride from toothpaste, well water, and other fluoridated sources may be inadequate to prevent caries, especially when other risk factors are present. These factors include a reduced saliva flow rate, increased consumption of foods and beverages that contain fermentable carbohydrate (that is, cariogenic substances), and reduced tooth cleaning ability. Saliva analyses indicate that residual fluoride concentrations in the mouth after long periods between tooth brushing decrease from 1 ppm or more to a range between 0.02 and 0.08 ppm. Because of this reduction in fluoride, remineralization may not be possible, since the transfer of calcium and phosphate ions into enamel depends on a sufficient and sustainable supply of fluoride ions. Furthermore, because the concentration of calcium ions in saliva is also very low in healthy individuals (a maximum of approximately 60 ppm), remineralization may be further retarded without an additional source of calcium.

It is well known that low concentrations of fluoride have a beneficial effect on enamel and dentin remineralization. For treatments to be effective over periods longer than the brushing time and the subsequent time for salivary clearance, fluoride must be deposited and slowly released. Calcium fluoride or similar deposits act in such a way because of a surface covering of phosphate and/or proteins, which make the CaF₂ less soluble under in vivo conditions than the pure form in inorganic solutions. Subsequently, in the presence of phosphate groups on the surface of calcium fluoride globules, fluoride is released with decreasing pH when the phosphate groups are protonated in dental plaque. Saliva alone has the ability to increase plaque pH with bicarbonates, although typically this process may take up to 2 hours. The susceptibility of apatite in enamel surface layers makes it critical to control the acidity of the plaque fluid and Ca²⁺ and PO₄³⁻ concentrations in saliva. The subsequent remineralization process is characterized by the reverse of this process. When the oral pH is restored to approximately 7, Ca²⁺ and PO₄³⁻ ions are incorporated into the depleted mineral layers of enamel as new apatite. The demineralized zones in the crystal lattice act as nucleation sites for new mineral deposition. In the presence of fluoride (at high concentrations), the original carbonated apatite (CAP) loses its remaining carbonate and is replaced by a hybrid of hydroxyapatite (HAP) and fluorapatite (FAP). This cycle is fundamentally dependent on enamel solubility and ion gradients. Essentially, the sudden drop in pH produces an undersaturation of these essential ions (Ca²⁺ and PO₄³⁻) in plaque fluid with respect to tooth mineral following meals. This promotes the dissolution of enamel. At neutral pH, the ion supersaturation of plaque produces a reverse shift in the equilibrium, causing a mineral deposition within the tooth surface.

Emerging technologies and materials that promote remineralization at early and moderately advanced stages of caries will be developed more rapidly as soon as the primary factors that dominate the remineralization process can be controlled effectively. In addition, more sensitive imaging or measurement processes are needed to validate early stages of remineralization and to more effectively determine whether or not preventive therapies produce optimal outcomes.

Bone-Grafting Materials

In addition to remineralizing small lesions, gross remineralizing treatments and bone grafts are increasingly needed for dentistry. Bone-grafting materials are necessary for various oral surgeries, such as alveolar ridge augmentation and sinus augmentation and for the placement of implants or to improve mandibular denture stability. Extraction socket grafting materials are gaining popularity to prevent the collapse of cortical bone and enable the placement of an implant. Also, patients prefer faster treatment with fewer surgeries, which is driving research toward single-stage implant procedures with immediate functional loading (IFL). Implants with nanotechnology coatings may increase the success and acceptability of the single-stage and IFL procedures, but before implant placement, grafts are often needed.

Graft materials are available containing allogeneic, xenogeneic, or synthetic hydroxyapatite particles to act as a scaffold for gradual replacement by the patient’s bone. These current bone grafts slowly resorb and the replacement bone densifies over months until a restorative denture or implant can be made. More rapid resorption and bone-growth-stimulating materials are needed to meet the demand for faster implant placement after tooth extraction, even immediate placement. Some available grafting materials are designed for faster resorption and bone growth. For instance, PepGen P-15 (DENTSPLY Friadent, Mannheim Germany), a hydroxyapatite product with an amino acid, is available for accelerating natural bone regeneration. Infuse (Medtronic, Minneapolis, MN), a collagen sponge with recombinant human bone morphogenetic protein-2 (rhBMP-2), is indicated for sinus augmentation and localized alveolar ridge augmentation. Bone morphogenetic proteins, also known as cytokines, represent a group of growth factors that can affect cell interactions and cell behavior. Perioglas and NovaBone Dental Putty (NovaBone Products, Jacksonville, FL) contain coarse (greater than 100 µm) bioglass particles for implantation as a resorbable scaffold for bone growth and periodontal grafting. “Ostim-Paste (aap Biomaterials GmbH, Dieburg, Germany) is a nanocrystalline hydroxyapatite paste that can be used to repair the intraoral bony defects that may result from cystectomies (a surgical procedure to remove a cyst), root tip resections, extractions, and surgical tooth removal and for augmentations in the areas of the alveolar processes and maxillary sinuses (sinus lift) as well as to fill periodontal defects. Clinical trials are needed to determine the success of each of these approaches and guide the development of future products.

New bioactive glasses are under development that contain more boron and silica than the original formulas of 45S5 bioglass (45 wt% SiO₂ and a 5:1 ratio of CaO to P₂O₅) for osteogenesis, and the new formulas may be resorbed more quickly with faster bone replacement. Copper or silver in these glasses may also enhance soft tissue deposition in other applications. Powders, fibers, or foams of the bioactive glasses may be used as scaffolds for use in the rapid replacement of bone or soft tissue. Scaffolds of bioactive glass are used for osteoconductivity, and they may also initiate chondrogenesis. The latter could be useful for temporomandibular joint (TMJ) treatments. Combinations of biodegradable polymers with bioactive glass particles may also enhance tissue replacement and serve as the basis for new grafting materials.

Stimulus-Responsive “smart” Materials

“Smart” materials are designed for interaction with external stimuli such as light, temperature change, stress, moisture, pH, or electric/magnetic fields (McCabe et al., 2009). Currently, these dental materials include (1) zirconia ceramics that transform from a tetragonal to monoclinic crystal form when tensile stress is induced at crack tips, leading to an increase in crystal volume and compressive stress that tends to prevent propagation of the cracks; (2) composites designed for initiation of curing by irradiation with particular wavelengths of blue light or composite cements that change color when irradiated (for use in orthodontics); (3) glass ionomer cement that when desicccated, weakens the cement to make it easier to remove orthodontic bands; and (4) glass ionomer restoratives that increase the release of fluoride when the pH in plaque fluid decreases (ten Cate et al., 1995).Nickel-titanium wires that soften when chilled below body temperature for bending are “smart” and very useful for threading together orthodontic brackets at the earliest treatment stages with the most misaligned teeth. Future smart materials may include cements that can be triggered to soften and allow debonding by a temperature change or irradiation process. Cements such as this would be very attractive for use with temporary crowns, orthodontics, and some implant restorations.

Emerging technologies and materials may also include smart hydrophilic resins that effectively seal moist microscopic crevices adjacent to defective restorations and release fluoride and/or other mineralizing agents when the pH of oral fluids decreases to a range of 4.0 to 5.5—that is, when enamel demineralization often occurs.

The use of sealants, varnishes, and composites that release fluoride is not new. However, most of the studies on these materials were based on commercial products whose compositions were not known precisely and whose ages at placement were unknown or not identified. In addition, few studies have analyzed the influence of particle composition, particle size, and particle size distribution, nor have they demonstrated the on-demand nature of “smart sealing materials.”

Secondary caries and the unnecessary replacement of defective restorations can be prevented and adjac/>