Review Article: Silver Nanoparticles in Dental Biomaterials
Review Article: Silver Nanoparticles in Dental Biomaterials
Review Article: Silver Nanoparticles in Dental Biomaterials
Review Article
Silver Nanoparticles in Dental Biomaterials
Juliana Mattos Corrêa,1 Matsuyoshi Mori,2 Heloísa Lajas Sanches,3 Adriana Dibo da Cruz,1
Edgard Poiate Jr.,1 and Isis Andréa Venturini Pola Poiate1
1
Department of Operative Dentistry, Fluminense Federal University, 28625-650 Nova Friburgo, RJ, Brazil
2
Prosthodontics Department, University of São Paulo, 05508-000 São Paulo, SP, Brazil
3
School of Chemistry, Rio de Janeiro Federal University, 21941-909 Rio de Janeiro, RJ, Brazil
Copyright © 2015 Juliana Mattos Corrêa et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Silver has been used in medicine for centuries because of its antimicrobial properties. More recently, silver nanoparticles have
been synthesized and incorporated into several biomaterials, since their small size provides great antimicrobial effect, at low filler
level. Hence, these nanoparticles have been applied in dentistry, in order to prevent or reduce biofilm formation over dental
materials surfaces. This review aims to discuss the current progress in this field, highlighting aspects regarding silver nanoparticles
incorporation, such as antimicrobial potential, mechanical properties, cytotoxicity, and long-term effectiveness. We also emphasize
the need for more studies to determine the optimal concentration of silver nanoparticle and its release over time.
nanoparticles also possess unique toxicity mechanisms [37]. solutions, rinsed with deionized water, dried, and irradiated
Because of that, a better understanding of AgNPs safety is with UV light from a high-pressure Hg lamp. This process
need, in order to increase their clinical use [38]. allows producing samples with different Ag concentrations,
Nanotechnology provides a wide range of possibilities depending on the AgNO3 solution concentration [49].
to develop new antimicrobial materials [3]. However, there Another difference is related to the form of AgNP obtain-
are disadvantages, for example, color change, an important ment. In some studies the particles are commercially avail-
property of dental materials [39]. In this review, we dis- able, so they are obtained directly from the producer [50–52].
cuss AgNPs incorporation into dental materials, such as In others, AgNPs are prepared by reduction of AgNO3 , with
composite resin and adhesive systems, acrylic resin, root NaBO4 [22], polyvinylpyrrolidone [21], sodium citrate [44],
canal fillings, and implants, highlighting aspects regarding and gallic acid [48], among others.
microorganism growth inhibition, cytotoxicity, and physical
properties of these modified materials.
4. Composite Resin and Adhesive System
2. AgNPs Characterization Dental caries is still the most common and widespread oral
disease, having as the main etiologic agent the acidic attack
One important step for the development of AgNPs- from cariogenic bacteria, such as Streptococcus mutans and
containing materials is their characterization. Many studies Lactobacillus spp. [51]. Currently, the most widely dental
have analyzed the Ag dispersion [26, 28, 32, 40], through material used to treat caries lesions is composite resin,
Transmission Electron Microscopy (TEM). This technique especially because of its esthetics and load-bearing properties
allows visualizing how AgNPs spread into the tested material, [53–55]. Hence, many studies have been performed, in order
as well as to verify the particle size. to improve quality and durability of polymeric restorative
According to Cheng et al. [28], NAg particles of ∼3 nm materials [56–58].
were clearly visible and well dispersed throughout the poly- In spite of the notable advances obtained, composite
mer matrix. These results were confirmed in a subsequent restorations accumulate more biofilm than other restorative
study [29], in which authors reported NAg sizes ranging from materials [59–62]. This is especially important in cases of
2 to 5 nm. This very small size allows NAg penetration on failures on restoration margin [63]. Actually, although it is
dentinal tubules [40], which can represent the possibility wanted, the perfect sealing between the restorative material
of inactivating residual bacteria on dentine. Besides that, it and the cavity wall often does not occur [32]. It has been
has also been shown that AgNPs were well dispersed in the shown that there is microleakage on restoration margins, and
material with minimal appearance of nanoparticle aggregates these gaps can be colonized by oral bacteria, resulting in
[26, 32]. secondary caries [64], which makes necessary the restoration
Another important feature to be analyzed is the minimum replacement.
inhibitory concentration (MIC) of AgNPs. MIC is defined as In order to prevent or to diminish biofilm accumulation
the lowest concentration of antimicrobial agent at which 90% over composite and in the restorations margins, antimicrobial
growth is observed in the medium [46]. Hernández-Sierra restorative materials have been developed, especially through
et al. [47] used the liquid dilution method to find the MIC the incorporation of AgNPs to composite resins [24–26]
of 25 nm-AgNPs against S. mutans strains, and the results and adhesive systems [29, 32, 40–42, 50, 52, 65, 66]. These
showed an average MIC of 4.86 ± 2.71 𝜇g/mL, suggesting a materials are multiphase substances composed of an organic
higher antimicrobial effect of AgNPs. polymer matrix, filler particles, coupling agent (silane), and
In a similar study, Espinosa-Cristóbal et al. [48] tested the initiator-accelerator of polymerization [67], and AgNPs
different AgNPs sizes (8.4 nm, 16.1 nm, and 98 nm) and incorporation is based on the modification in the filler
they reported higher MICs than the abovementioned study: components [61].
101.98 ± 72.03 𝜇g/mL, 145.64 ± 104.88 𝜇g/mL, and 320.63 ±
A research developed by Cheng et al. [26] reported the
172.83 𝜇g/mL, respectively. This probably occurred because
effect of AgNPs incorporation, at different concentrations,
of the methodology, which included sucrose for S. mutans
to a composite resin, in order to investigate its mechanical
growing. Authors also verified that MICs were directly
properties and biofilm formation. In this study, composites
proportional to the particle size; it means, as bigger the size
were synthesized with AgNPs at 0.028, 0.042, 0.088, and
as higher the MIC.
0.175%. Mechanical properties of composites with AgNPs at
0.028% and 0.042% were similar to those with no AgNPs.
3. Forms of Incorporation Besides that, counts of colony forming units (CFU) for total
streptococci and S. mutans, using AgNPs at 0.042%, were 75%
AgNPs used in dental materials are incorporated through smaller than the control group without AgNPs. These data
distinct ways, depending on the type of material. For com- suggest that AgNPs incorporation to composite resins enables
posite resin and adhesive systems, the most common tech- good mechanical properties and notable antimicrobial poten-
nique is adding a monomer, usually 2-(tert-butylamino)ethyl tial, even at low concentration.
methacrylate, in order to improve Ag salt solubility in the In order to evaluate the influence of AgNPs incorporation
resin solution [28, 32, 40]. For dental implants, the process on bond strength to dental substrate, Melo et al. [41] added
is totally different: Titanium samples are soaked in AgNO3 AgNPs, at 0.1% by mass, to an adhesive system. The results
International Journal of Biomaterials 3
have shown that AgNPs did not compromise the bond have been satisfactorily incorporated into polymers used as
strength (𝑃 > 0.1), at the same time that it decreased tissue conditioners and as denture base [82–84]. The action
metabolic activity on biofilm, compared to control group mechanisms of AgNPs-incorporated polymers is still unclear,
without AgNPs. In this study it was also observed reduction of since some authors attribute the antimicrobial effectiveness to
CFU for total microorganisms, total streptococci, and mutans the silver ions release [85, 86] and others to the direct contact
streptococci (𝑃 < 0.05). between the material and the microorganisms [87].
Li et al. [32] performed a study incorporating of AgNPs, Acosta-Torres et al. [43] developed a PMMA containing
at 0.05% by mass, to an adhesive system, aiming to assess 1 𝜇g/mL of AgNPs and they compared this new compound
bacterial inhibition provided by this antimicrobial, in both to unmodified PMMA. It has been observed that PMMA-
short and long distance. It has been reported that AgNPs AgNPs specimens showed significantly less Candida albicans
reduced CFU number and acid lactic production on biofilm adherence compared to PMMA (𝑃 < 0.05), demonstrating
over and away to the adhesive surface, evidencing that the antifungical potential of AgNPs incorporated to acrylic
AgNPs-containing adhesives enable long-distance antibacte- resin. Besides that, they evaluated the activity of mouse
rial potential. fibroblasts and human lymphocytes, and it has been shown
Another important aspect to be assessed is the biocom- that PMMA-AgNP compound does not present cytotoxity or
patibility of AgNPs-containing restorative materials. Accord- genotoxicity. These results suggest that the novel acrylic resin
ingly, Zhang et al. [42] have studied the effects of AgNPs incorporated with AgNPs could be developed as a denture
incorporation, at 0.05% by mass, to a primer and an adhesive, base.
regarding human gingival fibroblast viability. It has been In a study performed by Monteiro et al. [44] AgNPs
shown that AgNPs addition did not affect the cytotoxicity of were incorporated in a commercial acrylic resin, in different
primer and adhesive tested, evidencing the clinical applica- concentrations (0.05%, 0.5%, and 5% of AgNPs, by mass). The
bility of this antimicrobial. authors evaluated the mechanical properties of the modified
Based on abovementioned studies, it is possible to say resin, as well of the unmodified one (0% of AgNPs). There-
that the antibacterial effects of AgNPs-containing restorative unto, the flexural strength test was performed, and it was
materials might decrease the development of recurrent caries, observed that all the groups presented very similar flexural
to increase the longevity of tooth restorations, and to be resistance values, suggesting that AgNPs incorporation does
effective in decreasing the formation of bacterial biofilms not affect the mechanical properties of acrylic resin.
on teeth and restorations, without compromising mechanical When dentures are ill-fitted is recommended recovering
properties and cytotoxicity of composite resins and adhesive his base with tissue conditioners, which are easily degradable
systems. with time and occasionally susceptible to microbial coloniza-
tion [88]. Thus, AgNPs incorporation could also be profitable
in this material and not only in dentures base.
5. Acrylic Resin Accordingly, Nam [21] has incorporated AgNPs into a
Dentures, mostly constituted by poly(methyl methacrylate) commercial tissue conditioner, in the following concentra-
(PMMA) acrylic resin [68], have their inner surface con- tions: 0.1%, 0.5%, 1.0%, 2.0%, and 3.0%. Their inhibitory effect
siderably rough [69], and this roughness, allied to other was evaluated against Staphylococcus aureus, Streptococcus
factors (e.g., poor hygiene, xerostomy, and HIV infection), mutans, and Candida albicans after 24 h and 72 h. The authors
contributes to the emergence of denture stomatitis [70, have reported that the modified tissue conditioner presented
71]. This pathology, characterized by red focal area, mostly antimicrobial properties even at lower concentrations, that is,
localized in palatal mucosa, is present in 50–70% of complete 0.1% (for S. mutans and S. aureus) and 0.5% (for C. albicans).
denture wearers [72, 73], and it is frequently associated with
Candida species colonization. These fungi colonize denture 6. Endodontic Materials
surfaces forming a biofilm [74], which acts as a key-factor to
denture stomatitis development [75]. Several studies have demonstrated that bacteria are the main
The treatment of denture stomatitis is based on topical or etiologic agent of pulpal infection and periradicular lesion
systemic antifungical drugs, for example, fluoconazole and formation [89–91]. The microbiota of infected root canals is
nystatin [76–78]. However, this infection is often persistent, polymicrobial and is dominated by Gram-negative anaerobes
since antifungical resistance has been reported in Candida [92, 93]. It has been demonstrated that the presence of
biofilms [75]. Moreover, it has been observed that Candida residual bacteria in root canal is connected with significantly
species present in biofilms are less susceptible to antifungical higher rates of treatment failure [94].
drugs than planktonic cells [79–81]. Another problem related Since elimination of bacteria in root canals is the key to
to denture stomatitis is that many geriatric prosthetic wearers treatment success [95], endodontic materials should ideally
present difficulties on keeping the denture clean, due to provide some antimicrobial activity [96, 97], in order to
their reduced motor dexterity, memory loss, and cognitive improve the prognosis of endodontically treated teeth [98].
impairment [21]. Various materials have been used as root canal fillings, among
Considering the aforementioned factors, denture stom- which gutta-percha is one of the most used [95]. This material
atitis represents a challenge for dentistry, and methods for has been proved to present slight antibacterial property,
its prevention, should be encouraged. Accordingly, AgNPs provided by the zinc oxide in its components; however, this
4 International Journal of Biomaterials
does not provide to gutta-percha an effective bactericidal Several measures have been proposed to avoid bacterial con-
potential [98]. tamination, such as implant disinfection and aseptic surgical
Accordingly, Iranian researchers [45] have introduced protocols; nevertheless, bacterial invasion often occurs after
nanosilver-gutta-percha, as an attempt to improve the surgery [109].
antibacterial effect of gutta-percha. The new material, which In order to prevent biofilm formation over implants
is standard gutta-percha coated with AgNPs, has demon- surface, antibacterial coatings have been developed; however,
strated significant effect against Enterococcus faecalis, Staphy- most of them present poor long-term antibacterial action
lococcus aureus, Candida albicans, and Escherichia coli. and also the possibility of generating resistant strains after
Besides that, Shantiaee et al. [99] have tested the biocom- prolonged use [110–112]. In this context, AgNPs incorporation
patibility of this new material, by comparing the cytotoxicity to implant surface has been suggested [109, 113], since it would
of nanosilver-coated gutta-percha and normal gutta-percha be possible to produce coatings with long-term antibacterial
on mouse fibroblasts. In this study, after 24 hours, nanosilver- properties by controlling Ag release [23].
coated gutta-percha presented cytotoxicity similar to normal In study performed by Zhao et al. [23], AgNPs were incor-
gutta-percha and, after one week, it reached the lowest level porated into titania nanotubes (TiO2-NTs) on Ti implants,
of cytotoxicity among the tested materials. in a process involving silver nitrate immersion and ultravio-
Other important step in the endodontic treatment is let radiation. The antibacterial effect against Staphylococcus
the chemomechanical debridement of pulpal tissue and aureus was assessed, and results have shown inhibition of
pathogenic bacteria. In this stage, irrigant solutions should planktonic bacteria during the first several days. Moreover,
be used, for dissolving tissue and disinfecting the root canal AgNPs-coating Ti implants have presented ability to prevent
system [100]. For this purpose, sodium hypochlorite (NaOCl) bacteria adhesion for up to 30 days, which are considered
has been used for more than 70 years, and it remains as one of sufficient time to prevent post-infection in early stages.
the most common solutions [101]. However, if NaOCl passes In a similar study, Flores et al. [22] have evaluated the
beyond the apex, it is extremely toxic to the periapical tissues antibacterial activity of AgNPs against Pseudomonas aerugi-
[102]. nosa. It has been reported that the number of total cells found
In this context, Lotfi et al. [20] performed a study com- on AgNP-modified implants represents only 20% of those
paring the antibacterial effect of NaOCl and AgNP solution attached to unmodified surfaces. This data suggests that the
against Enterococcus faecalis, which is a bacterium often iso- incorporation of AgNPs on Ti implants is an efficient method
lated from failed endodontic treatment cases [103]. Authors to protect implant surface against pathogen colonization.
have observed that there were no significant differences As important as the antibacterial potential is the biocom-
among 5.25% NaOCl and 0.005% AgNPs, suggesting that this patibility of these modified implants. Aiming to evaluate this
solution, in a remarkably lower concentration, possesses the property, Lu et al. [114] have tested Ti implants incorporated
same bactericidal effect as 5.25% NaOCl; hence, it could be with different concentrations of AgNPs (0.5, 1, 1.5, 2 M). For
used as a new intracanal irrigant. all the tested concentrations, osteoblasts started to adhere on
Another important endodontic material is the mineral the coatings after 1 day of culture and spread well until 7
trioxide aggregate (MTA), used in many indications such as days of culture. However, after this, the inhibitory effect of
perforations sealing, external/internal root resorption repair, 1 M Ag on cell proliferation became significant, suggesting
and apexification [104, 105]. In spite of being a material of that AgNP coatings with low amounts of silver were more
wide application, the antimicrobial properties of MTA are favorable for osteoblasts growth.
controversial, and they seem to be limited [106, 107].
Aiming to improve its antimicrobial potential, Samiei et 8. Future Perspectives
al. [19] modified MTA by adding AgNPs, at 1% weight. Its
effect against oral bacteria and fungi species was assessed. As shown in the previous paragraphs, AgNPs-containing
Results have showed that AgNPs-containing MTA possesses dental materials present good antimicrobial properties
higher antimicrobial effect against Enterococcus faecalis, Can- (Table 1). However, much is still to be discovered. One of
dida albicans, and Pseudomonas aeruginosa, compared to the most important experiments to be performed is to apply
unmodified MTA. the bench results on in vivo studies [29, 52], since laboratory
Although AgNP is a promising antimicrobial, there are conditions do not exactly reproduce oral conditions. Other
only a few studies employing it in endodontic materials. aspect to be investigated is the long term effectiveness of
And considering that endodontic treatment success is highly AgNPs applied on dental materials [32, 51], whereas a long
connected to the bacteria elimination, researches involving lasting antimicrobial potential of them is desirable.
AgNPs incorporation to root canal filling materials and
intracanal irrigators should be encouraged. 9. Conclusions
7. Titanium Implants In this review, the antimicrobial effect of AgNPs incorpora-
tion into dental materials was investigated, such as composite
Titanium (Ti) implants, widely used in dentistry, usually resin, endodontic materials, acrylic resin, and implants.
present infection around their surface, which remains one of Several studies have shown that silver, in its nanoparticulated
the most important complications in Implantology [49, 108]. form, possesses an inhibitory effect against many bacteria
International Journal of Biomaterials 5
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Conflict of Interests nated catheter,” International Journal of Antimicrobial Agents,
vol. 23, no. 1, pp. S75–S78, 2004.
The authors declare that there is no conflict of interests [8] G. Gosheger, J. Hardes, H. Ahrens et al., “Silver-coated megaen-
regarding the publication of this paper. doprostheses in a rabbit model—an analysis of the infection rate
and toxicological side effects,” Biomaterials, vol. 25, no. 24, pp.
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