Silver nanoparticles in dentistry
Introduction
The use of silver in oral care has been known for centuries and gained worldwide spread in the 19th century as one the main components in dental amalgams used for tooth restoration. Its use in amalgams has been reduced since 1930 as they were progressively substituted by esthetic polymer-based resins [1]. Since nanoscience has evolved and the outstanding antimicrobial properties of nanostructured silver-based formulations have been demonstrated against microorganisms such as bacteria, viruses, and fungi [2], [3], [4], [5], [6], [7], [8], the interest in silver has been renewed, and several promising new technologies are currently under development, especially in dental materials. In this context, AgNPs have been demonstrated to be effective antimicrobial components in prosthetic materials [9], adhesives [10], [11], and implants [12], [13], to promote caries arrestment [14], to prevent biofilm formation [15], and for osteogenic induction [16]. Fig. 1 shows the increasing interest in AgNPs in the 21st century in dentistry. As a result, it is reasonable to foresee that, in the near future, AgNPs will play an important role in oral healthcare.
Silver has a [Kr]4d105s1 electron configuration. Since the 4d shell does not effectively shield the 5s1 electrons, they are strongly attracted to the nucleus, and a relatively high standard reduction potential is observed (E0(Ag+/Ag) = +0.799 V). Hence, metallic silver is rather unreactive. On the other hand, silver has the lowest first ionization potential in Group 11 and thus, Ag+ is the most stable species in aqueous solutions, including physiological fluids, and in solids. Due to the filled 4d orbital, Ag+ compounds present a significant covalent character and they do not tend to form organometallic compounds. In addition, they do form complexes with coordination numbers as low as 2 [17]. Silver ions form bonds preferably with sulfur but also with nitrogen and oxygen. So Ag+ can bind to enzymes with S-pending groups as well as N atoms from nucleic acids [18]. Besides formulations containing Ag+, other silver-based compounds have also been successfully applied in dentistry. For instance, the linear complex [Ag(NH3)2+]F, which was recently cleared for caries arrestment in the US, is used in Japan for more than 80 years [19], [20]. However, with the development of nanotechnologies, AgNPs have gained most of the focus.
It is now possible to produce AgNPs with controlled size and morphology, high homogeneity (i.e. low polydispersity index) [21], and specific target functions, (i.e. functionalized with molecular capping agents, from small hydrophilic and hydrophobic chemical groups to large biomacromolecules, such as proteins) [22]. The nucleation and growth process of AgNPs can be mediated both by synthetic reagents and by biologically available products from plants and microbes [23], [24], [25]. As the nanoparticle composition, particle size distribution, morphology and surface chemistry can be finely tuned [26], [27], [28], AgNPs can access different sites in the oral cavity; in such a way they can currently be conceived as multifunctional building blocks [29] for dental materials and dentistry protocols.
Recent scientific achievements demonstrated the benefits of the use of AgNPs in dentistry as antimicrobial agents in a wide range of applications, preventing the need for infection therapies in several cases [30]. AgNPs have shown a very high antimicrobial effect, in comparison with several antimicrobial molecules, with good biocompatibility [9], [31], [32]. They can also act synergistically with several types of antibiotics [33], [34], [35], [36]. Furthermore, AgNPs have been used as the main agent in inorganic and polymeric-based antimicrobial (nano)composites [24], [37], [38]. Also, important studies have been carried out in order to elucidate the potential risks to human health, and through environmental exposure of AgNPs, thus trying to delimit the safe use of AgNPs-based products and technology [39], [40], [41]. Multiple and broad aspects of AgNP synthesis, processing, applications and toxicology have been well covered in recent reviews [8], [21], [22], [23], [24], [25], [39], [40], [41], [42], [43]. In the last three years, some influential reviews with different focuses on the application of nanotechnology in dentistry have been published [6], [7], [44], [45]. However, aspects involving AgNPs production and nanobiotechnological applications were reviewed only in a general sense, and not specifically for dentistry [31], [46]. Also, their applications in dental biomaterials covered specifically implants and their incorporation into nanocomposites [47].
In this review, the perspectives related to AgNPs-based technologies aimed at oral care are presented in detail, and organized by their application in (i) nanocomposites, (ii) implant coatings, (iii) pre-formulation with antimicrobial activity against cariogenic pathogens, periodontal biofilm, fungal pathogens and endodontic bacteria, and (iv) other applications (local anesthesia and oral cancer). Recent achievements in the study of the mechanism of action of AgNPs are also presented, as well as the most important toxicological aspects.
Section snippets
Mechanistic aspects of silver acting on bacteria
Although the antibacterial mechanism of AgNPs has not been fully elucidated, some aspects of the antimicrobial action of AgNPs have been recognized. Silver ions are capable of acting on different structures of the bacterial cell. Primarily, these ions seem to adhere to the cell wall and cytoplasmic membrane through electrostatic attraction and affinity to sulfur proteins, thus enhancing the permeability of the membrane and also leading to disruption of these structures [48], [49]. In
Application of AgNPs in nanocomposites
AgNPs have been incorporated into tissue conditioner, denture resins, and other biomaterials [69], [70], [71]. Antifungal effect against Candida albicans has been demonstrated when AgNPs were added to poly(methyl methacrylate) (PMMA) resins for dentures [72] and silicone-based soft liners [73]. This microorganism may cause denture stomatitis and mucosal infections. Nanocomposites of acrylic resins and AgNP (∼38 nm) have also shown a strong antimicrobial effect against Escherichia coli together
Implants modified with AgNPs
The coating of implants has been a strategy to hamper bacterial adhesion to their surfaces and also to stimulate osseointegration and fibroblast proliferation. AgNPs together with other antibiotics have been tested in coating formulations, showing favorable results regarding antimicrobial activity. AgNPs were used in combination with tantalum nitride for the coating of titanium substrates. The composites with a silver concentration of 21.4 wt% presented significant antibacterial effect against
Antimicrobial activity against cariogenic pathogens
A healthy human oral microbiota has around 600 microorganisms living in different habitats such as teeth, tongue, cheeks and gingival sulcus [98]. They are mainly bacteria, viruses and fungi and many of them co-evolved with our species through mutualism [99]. Tooth decay and gingivitis are two of the most prevalent bacterial diseases. Dental caries is a condition caused by a specific biofilm that produces acid, leading to tooth enamel and dentin demineralization. It is a global and costly oral
Other applications
Besides the dental applications already mentioned, AgNPs have been investigated as interesting tools in the treatment and diagnosis of different cancers [8], [121]. Nevertheless, studies of the potential use of AgNPs in the treatment of oral cancer are scarce. One of the most important cancers that affect the oral cavity is squamous cell carcinoma. This cancer makes up 90% of head and neck cancers and includes a class of epithelial cancers originating from the oral or nasal cavity, paranasal
Toxicity of AgNPs
Although the use of AgNPs improves the performance of dental materials, proactive approximations might also be introduced to establish safe conditions for the use of AgNPs in dentistry. The toxicity of AgNPs was demonstrated to be directly related to the activity of free Ag+ ions released in the medium [130], [131]. Another concern exists about the capability of AgNPs to cross the blood-brain barrier (BBB) through trans-synaptic transport, with final accumulation in the brain [132]. In vitro
Conclusions
By comparing to the clinical uses of AgNPs in medicine, such as to treat skin infections as wound dressings [143] and in the prevention of infections with silver-impregnated central venous catheters [144], most of results in dentistry have been in vitro, focusing on the antimicrobial efficacy of silver-based systems. Recent studies though have demonstrated excellent antimicrobial activity of AgNPs in materials such as nanocomposites, acrylic resins, resin co-monomers, adhesives, and implant
Acknowledgments
Support from São Paulo Research Foundation (FAPESP), National Council for Scientific and Technological Development (CNPq), INOMAT (MCTI/CNPq), NanoBioss (MCTI) is acknowledged. The authors thank F. Rangel for electron microscopy images.
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