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Nanoparticles based on metal and metallic oxides have become a novel trend for dental applications. Metal nanoparticles are commonly used in dentistry for their exclusive shape-dependent properties, including their variable nano-sizes and forms, unique distribution, and large surface-area-to-volume ratio. These properties enhance the bio-physio-chemical functionalization, antimicrobial activity, and biocompatibility of the nanoparticles. Copper is an earth-abundant inexpensive metal, and its nanoparticle synthesis is cost effective. Copper nanoparticles readily intermix and bind with other metals, ceramics, and polymers, and they exhibit physiochemical stability in the compounds. Hence, copper nanoparticles are among the commonly used metal nanoparticles in dentistry. Copper nanoparticles have been used to enhance the physical and chemical properties of various dental materials, such as dental amalgam, restorative cements, adhesives, resins, endodontic-irrigation solutions, obturation materials, dental implants, and orthodontic archwires and brackets. The objective of this review is to provide an overview of copper nanoparticles and their applications in dentistry.
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Citation: Xu, V.W.; Nizami, M.Z.I.;
Yin, I.X.; Yu, O.Y.; Lung, C.Y.K.; Chu,
C.H. Application of Copper
Nanoparticles in Dentistry.
Nanomaterials 2022,12, 805.
Academic Editors: Krasimir Vasilev
and Takuya Kitaoka
Received: 28 January 2022
Accepted: 25 February 2022
Published: 27 February 2022
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Attribution (CC BY) license (https://
Application of Copper Nanoparticles in Dentistry
Veena Wenqing Xu , Mohammed Zahedul Islam Nizami * , Iris Xiaoxue Yin, Ollie Yiru Yu ,
Christie Ying Kei Lung and Chun Hung Chu
Faculty of Dentistry, University of Hong Kong, Hong Kong 999077, China; (V.W.X.); (I.X.Y.); (O.Y.Y.); (C.Y.K.L.); (C.H.C.)
Nanoparticles based on metal and metallic oxides have become a novel trend for dental
applications. Metal nanoparticles are commonly used in dentistry for their exclusive shape-dependent
properties, including their variable nano-sizes and forms, unique distribution, and large surface-area-
to-volume ratio. These properties enhance the bio-physio-chemical functionalization, antimicrobial
activity, and biocompatibility of the nanoparticles. Copper is an earth-abundant inexpensive metal,
and its nanoparticle synthesis is cost effective. Copper nanoparticles readily intermix and bind with
other metals, ceramics, and polymers, and they exhibit physiochemical stability in the compounds.
Hence, copper nanoparticles are among the commonly used metal nanoparticles in dentistry. Copper
nanoparticles have been used to enhance the physical and chemical properties of various dental
materials, such as dental amalgam, restorative cements, adhesives, resins, endodontic-irrigation
solutions, obturation materials, dental implants, and orthodontic archwires and brackets. The
objective of this review is to provide an overview of copper nanoparticles and their applications
in dentistry.
Keywords: copper nanoparticles; antimicrobial; dentistry
1. Introduction
Copper is a popular element in medical and dental research due to its antimicrobial
properties and low toxicity [
]. The antimicrobial activities are induced by either copper’s
metal ions or the oxidized cupric ions derived from copper nanoparticles (1–100 nm).
Moreover, copper is readily available for the synthesis of copper nanoparticles, so it is
cost effective [
]. Copper nanoparticles can be processed either naturally or via chemical
synthesis [
]. In addition, they can easily oxidize in air or water and produce copper oxide
nanoparticles. Like most metal nanoparticles that are commonly used in dentistry, copper
particles have variable nano-sizes and forms, a unique distribution, and a large surface-
area-to-volume ratio. These properties enhance the bio-physio-chemical functionalization,
antimicrobial activity, and biocompatibility of the nanoparticles. Reports have shown
that copper oxide nanoparticles are antimicrobial and inhibit biofilm formation [
]. The
high surface-area-to-volume ratio of copper nanoparticles enhances their antimicrobial
ability [
]. These nanoparticles’ antibacterial activities have been widely investigated,
although the exact mechanism of copper nanoparticles against microbes is not
clear [1113]
Copper nanoparticles have demonstrated higher bactericidal activity against E. coli, B.
subtilis, and S. aureus compared with silver nanoparticles, which are one of the nanoparticles
commonly used nanoparticles in biomedical research [14,15].
Researchers want to develop dental materials that have antimicrobial properties to
prevent oral infection. Copper nanoparticles exhibit antimicrobial activities and other
metallic properties associated with dental applications. Preparing these nanoparticle
composites with existing dental materials is easy and is said to be physiochemically stable.
Still, they have a very limited clinical application. In dentistry, copper nanoparticles
have mostly been studied as a modifier in amalgam and antimicrobial agents. Recently,
Nanomaterials 2022,12, 805.
Nanomaterials 2022,12, 805 2 of 15
several dental materials were studied with regard to copper nanoparticles, and it was
reported that copper nanoparticles can be added to dental cements, restorative materials,
adhesives, resins, irrigating solutions, obturations, orthodontic archwires and brackets,
implant surface coatings, and the bone regeneration process [
]. The results were
impressive but a bit ambiguous for clinical applications.
A search in PubMed using ((copper nanoparticles) AND (dentistry OR dental)) found
no relevant review articles. The aim of this review is to highlight the research directions,
their outcomes, and the feasibility of future studies. Therefore, we performed a systematic
search of the publications in English and included the maximum number of works in the
literature. We searched three common databases, namely, EMBASE, Google Scholar, and
MEDLINE. In the search, the keywords were (copper OR (copper nanoparticles) OR (copper
nanocomposite)) AND (dentistry OR (dental material)). These keywords covered as much
information about copper nanoparticles in dentistry as possible without overlooking related
research. This review includes all publications on the application of copper nanoparticles
in dentistry. Abstracts, editorials, and letters to the editor were excluded. Among the
vast number of articles reviewed, we have summarized the dental materials with copper
nanoparticles into four main categories. They are metals and alloys, polymers and resins,
restorative cements, and miscellaneous dental materials.
2. Antibacterial Mechanism of Copper Nanoparticles
Copper is a well-established antimicrobial and anti-inflammatory agent with a long
history of medicinal applications [
]. The nano-sized particles and high surface-area-to-
volume ratio allow copper nanoparticles to exhibit broad-spectrum antibacterial and antivi-
ral activities [
]. Copper nanoparticles may have a similar mode of action as other metal
nanoparticles. Although several studies have shown that copper-nanoparticle-containing
materials demonstrate antibacterial activity and biocompatibility, related antibacterial
mechanisms are not inclusive [
]. A few studies were conducted in an attempt to ex-
plore the antibacterial mechanism of copper nanoparticles. Mainly, three hypothetical
mechanisms were commonly described. First, copper nanoparticles accumulate in the
bacterial membrane and change its permeability. They then remove membrane proteins,
lipopolysaccharides, and intracellular biomolecules and cause the dissipation of the proton-
motive energy around the plasma membrane [
]. Second, reactive oxygen species
from nanoparticles (in the form of nanoparticles or ions) process post-oxidative dam-
age in cellular structures [
]. Third, cells’ uptake of ions (generated via nanoparti-
cles) decreases intracellular adenosine triphosphate production and deoxyribonucleic acid
(DNA) replication [3134].
Studies demonstrated that the carboxyl group of bacterial lipoproteins has a negative
charge that attracts positive copper ions. After binding with copper ions, bacterial cell
membranes and their permeability change, and copper ions enter the cells. When they
merge with phosphorus- and sulfur-containing biomolecules (i.e., DNA), the copper ions
alter the cell structures and cell proteins. This alteration inhibits the cell’s biochemical
processes and causes cell death [
]. However, copper ions inhibit enzymatic activity.
They alter DNA or protein synthesis, inactivate their enzymes, and promote hydrogen
peroxide production [
]. In addition, nanoparticles denature protein molecules by inter-
acting with their sulfhydryl group [
]. At the same time, DNA, ribonucleic acid, proteins,
and cytoplasm leak out through the permeable membrane, causing cell damage that kills
bacteria [38]
. Furthermore, several other hypotheses of possible modes of copper nanopar-
ticle and bacterial interaction exist, such as the permeabilization of the plasma membrane,
the peroxidation of membrane lipids, changes in proteins, the inhibition of protein assem-
bly and activity, and the deformation of nucleic acids [
]. In most cases, all of these are
directed in the same way. We believe that further
in vitro
in vivo
studies should be
conducted to produce a systematic outline [40].
Many studies investigated copper nanoparticles’ antibacterial activities. However, few
studies reported their antiviral action. They demonstrated that copper nanoparticles target
Nanomaterials 2022,12, 805 3 of 15
the viral genome, especially encoding the genes responsible for viral infections [
In addition, some studies showed a similar reactive oxygen species process in the viral
envelope or capsid, which resembles antibacterial activity [
]. Viruses are more vulnerable
to injuries induced by copper nanoparticles because, unlike bacteria and fungi, they do
not have a repair mechanism. This leads to instant cell death [
]. Processes that cause
the immediate inactivation of microbes upon contact are known as “contact killing” [
In many studies, researchers have taken advantage of this “contact killing” property and
have created copper-nanoparticle-functionalized antiviral surfaces. Copper nanoparticles
are co-integrated into surface research to increase “contact killing”, as well as to develop
antibacterial and antiviral combination effects [
]. Figure 1demonstrates the mechanism
of copper nanoparticles’ antibacterial activities in bacterial cells.
Nanomaterials 2022, 12, x FOR PEER REVIEW 3 of 14
Many studies investigated copper nanoparticles’ antibacterial activities. However,
few studies reported their antiviral action. They demonstrated that copper nanoparticles
target the viral genome, especially encoding the genes responsible for viral infections
[21,41]. In addition, some studies showed a similar reactive oxygen species process in the
viral envelope or capsid, which resembles antibacterial activity [21]. Viruses are more vul-
nerable to injuries induced by copper nanoparticles because, unlike bacteria and fungi,
they do not have a repair mechanism. This leads to instant cell death [39]. Processes that
cause the immediate inactivation of microbes upon contact are known as “contact killing”
[42]. In many studies, researchers have taken advantage of this “contact killing” property
and have created copper-nanoparticle-functionalized antiviral surfaces. Copper nanopar-
ticles are co-integrated into surface research to increase “contact killing”, as well as to
develop antibacterial and antiviral combination effects [43]. Figure 1 demonstrates the
mechanism of copper nanoparticles’ antibacterial activities in bacterial cells.
Figure 1. Antibacterial mechanism of copper nanoparticles.
1. Attach to the cell wall and release copper ions.
2. Adhere to the cell membrane and enter the cell.
3. Disrupt the cell wall and membrane, denature protein, interrupt enzymatic activity, interrupt
deoxyribonucleic acid (DNA) replication, and interrupt adenosine triphosphate (ATP) produc-
4. Generate reactive oxygen species. Reactive oxygen species further interrupt DNA replication and
initiate the breakdown of DNA, denature ribosomes, and denature protein.
3. Copper Nanoparticles in Dental Materials
Copper nanoparticles present antimicrobial and bio-physio-chemical properties.
They enrich the material pool to minimize the shortage of dental materials in various clin-
ical applications. Generally, copper nanoparticles are used in dental metals and alloys,
dental polymers and resins, dental cements, and miscellaneous dental materials (Table 1).
Figure 1. Antibacterial mechanism of copper nanoparticles.
1. Attach to the cell wall and release copper ions.
2. Adhere to the cell membrane and enter the cell.
Disrupt the cell wall and membrane, denature protein, interrupt enzymatic activity,
interrupt deoxyribonucleic acid (DNA) replication, and interrupt adenosine triphos-
phate (ATP) production.
Generate reactive oxygen species. Reactive oxygen species further interrupt DNA
replication and initiate the breakdown of DNA, denature ribosomes, and
denature protein
3. Copper Nanoparticles in Dental Materials
Copper nanoparticles present antimicrobial and bio-physio-chemical properties. They
enrich the material pool to minimize the shortage of dental materials in various clinical
applications. Generally, copper nanoparticles are used in dental metals and alloys, dental
polymers and resins, dental cements, and miscellaneous dental materials (Table 1).
Nanomaterials 2022,12, 805 4 of 15
Table 1. Properties, applications, and functions of dental materials with copper nanoparticles.
Materials [Reference(s)] Properties Applications Functions
Dental metals and alloys
Copper-coated metal [44,45] Offer antimicrobial properties Denture framework Prevent stomatitis
Copper amalgam alloy [4649]Improve microstructural
Improve mechanical properties Amalgam restoration Prevent corrosion
Copper-linked alloy [5056] Offer antimicrobial properties Dental implant Prevent implantitis
Magnesium–copper alloy [57,58] Offer antimicrobial properties Dental implant Prevent implantitis
Titanium–copper alloy [5771] Offer antimicrobial properties Dental implant Prevent implantitis
alloy [72]Offer antimicrobial properties Dental Implant Prevent implantitis
Nickel–titanium–copper alloy
Enhance mechanical properties
Enhance thermal properties
Prevent galvanic corrosion
Reduce alloy aging
Orthodontic bracket
Orthodontic archwire
Facilitate orthodontic
tooth movement
Dental polymers and resins
acrylic resin [80]Offer antimicrobial properties Denture soft liner Prevent stomatitis
Copper-doped mesoporous
bioactive glass nanosphere acrylic
resin [81]
Facilitate copper-ion release
Offer antimicrobial properties Denture acrylic base Prevent stomatitis
Copper nanoparticles with
adhesive resin [82]Offer antimicrobial properties Dental adhesive Prevent secondary caries
Polyacrylic acid–copper iodide
nanoparticles with adhesive resin [83]Offer antimicrobial properties Dental adhesive Prevent secondary caries
Dental Cements
Copper [8486] Offer antimicrobial properties Lining materials Prevent secondary caries
Copper(I)-catalysed azide-alkyne
cycloaddition composites [87]Reduce shrinkage stress Composite resin
restoration Prevent secondary caries
Copper nanoparticles incorporated in
glass ionomer cement [88]Offer antimicrobial properties Glass ionomer
restoration Prevent secondary caries
Copper ions releasing blue calcium
phosphate cement [89]
Offer antimicrobial properties
Improve cytocompatibility
Regenerative dental
material Promote bone formation
Functionalized copper phosphate
nanoparticles [90,91]
Increase vascularization
Enhance bone regeneration
Regenerative dental
material Promote bone formation
Copper-modified zinc oxide
phosphate [92]Reduce marginal gap Luting cement Prevent secondary caries
Miscellaneousdental materials
Copper nanoparticles [93102]Enhance anti-inflammatory
effects Periodontal therapy Prevent inflammation
Copper-based substance [103107] Offer antimicrobial properties Endodontic irrigation solution
Endodontic paste Prevent apical reinfection
Nano copper-nonstoichiometric
dicalcium silicate [108]
Offer antimicrobial properties
Facilitate tissue regeneration Regenerative dental material Promote bone formation
Copper-doped biphasic calcium
phosphate [109,110]
Improve bone regeneration
Act as a bone substitution Synthetic bone graft material Promote bone formation
Graphene oxide copper
nanocomposite [111]Enhance bone regeneration Regenerative dental material Promote bone formation
3.1. Copper Nanoparticles in Dental Metals and Alloys
Prosthesis-induced inflammatory diseases, such as stomatitis and peri-implantitis,
pose challenges in clinical dentistry. Several strategies have been applied to solve these
problems. However, no specific solution has yet been found. Copper nanoparticles may
play a role in controlling infections. Copper nanoparticles destroy genomic and plasmid
DNA, making them an ideal alternative to antimicrobial surface coatings [
]. In addi-
tion, copper nanoparticles’ “contact killing” ability may also be well considered. Copper-
Nanomaterials 2022,12, 805 5 of 15
nanoparticle-incorporated removable and fixed partial denture framework designs could
solve denture-induced stomatitis and oral infections [45].
Dental amalgam restoration occupies a unique position in dentistry. These amalgam
alloys are broadly known as low-copper (5% or less copper) and high-copper alloys (13%
to 30% copper). A study reported that through the increasing of their copper density,
conventional dental amalgam alloys improved their microstructural and mechanical prop-
erties. Reports have also revealed the disappearance of the gamma-2 phase in copper
content with more than 20 wt% [
]. High-copper amalgams remain the leading materials
in Europe, America, and other advanced markets. A report stated that non-gamma-2
amalgams had superior strength and corrosion resistance properties [
]. In addition,
high-copper amalgam alloys showed less marginal deterioration in clinical studies, result-
ing in durable restorations [
]. Studies revealed that through the increasing of copper
nanoparticles in amalgam, the gamma-2 phase can be eliminated to increase the amalgam’s
compressive strength [49].
Implant dentistry has always faced the problem of peri-implantitis. Microbial infection
is one of the most common postoperative complications of implant surgery to be resolved.
It is a complex situation, and, apparently, eliminating its occurrence is the only way to
overcome it. However, it is generally impossible to stop the incidence completely. The ad-
vanced biomaterial research confirmed that biofilm formation on the implant surface is the
main cause, and it leads to the serious consequences of implant-related
infections [112,113]
In recent decades, studies focused on developing new implant materials or applying var-
ious coatings on existing implants using nanoparticles to inhibit biofilm formation and
to prevent biofilm-related infections. Some studies involved applying antibiotic surface
coatings to metal implants to develop prolonged antimicrobial action [114,115]. However,
this process was not successful due to the unstable bond between the surface coatings
and implants, as well as the risk of antibiotic resistance due to the continuous release of
antibiotics in the body [
]. Many researchers have used copper nanoparticles for the
surface modification of metallic implants [118,119].
Nisshin Steel (Tokyo, Japan) made the first copper-linked antimicrobial stainless steel
for biomedical applications [
]. Several studies have reported using copper nanoparticles
as an antimicrobial surface coating on different types of medical-grade stainless steel, such
as 317L stainless steel [
], 316L stainless steel [
], 304 stainless steel [
and 420-copper stainless steel [
]. Some studies have reported using copper nanoparticles
for the development of a magnesium–copper alloy as an implant material [57,58]. Several
studies have also reported using copper nanoparticles for the surface modification of
titanium implants [
]. Moreover, some studies have shown that the titanium–copper
alloy exhibits antibacterial and anti-aging properties. The studies have also demonstrated
that these antimicrobial properties could be tuned via changing the copper concentration
of the alloy composition [
]. Another study stated that copper-containing mesoporous
bio-glass reduced bacterial activity and biofilm formation by releasing copper ions [
A study reported that copper nanoparticles coating dental implant healing caps in-
hibited bacteria and biofilm formation [
]. On the other hand, another report showed
that a copper-bearing titanium alloy implant exhibited anti-infective properties against
oral bacteria. They also demonstrated that a titanium–copper alloy not only inhibited
peri-implant infections but also possessed biocompatibility [
]. Copper-nanoparticle
hydroxyapatite is antibacterial. A study reported that a titanium–copper alloy and a
titanium-copper ion-doped hydroxyapatite inhibited oral bacteria [
]. A Titanium-copper
alloy reduced the formation of biofilms to prevent implant failure. It was also effective
against implantitis-associated oral bacterial species. Therefore, the study recommended
using a titanium–copper alloy as an alternative for dental implants [
]. These are still in
the laboratory stage, and, therefore, further clinical studies should be aimed at validating
the application of copper-nanoparticle-functionalized implants in clinical implant dentistry.
The inclusion of copper nanoparticles in a nickel–titanium alloy offers several benefits
in orthodontic appliances. Copper nanoparticles in archwire reduced loading stress and pro-
Nanomaterials 2022,12, 805 6 of 15
vided a relatively high unloading stress, which increased orthodontic tooth movement and
was explained as a lower stress hysteresis [
]. A study demonstrated that the addition
of copper nanoparticles to metallic orthodontic appliances developed clinical significance
in terms of hyperelasticity, conversion temperature, and load cycling behavior [
]. Studies
have furthermore reported that the presence of copper nanoparticles in the nickel–titanium
orthodontic archwire reduced the aging effect and galvanic corrosion [73,75].
Studies showed that copper–nickel–titanium wires improved mechanical and thermal
properties [
]. The addition of copper nanoparticles increased friction under both wet
and dry conditions [
]. Furthermore, a clinical study compared copper–nickel–titanium
archwire and nickel–titanium archwire for correcting mandibular incisor crowding and
found no impact on the correction of the crowding [
]. Another study found that the
benefits of the loading pattern of the copper–nickel–titanium wire obtained from the
laboratory were not reflected in the clinical settings. Therefore, further investigations were
suggested to ensure and control these wires’ clinical performance in orthodontic practice.
3.2. Copper Nanoparticles in Dental Polymers and Resins
A heat-cured thermoset denture base with copper oxide nanoparticles is effective to
inhibit the growth of C. albicans, which is mainly responsible for denture stomatitis [
Moreover, another study found that copper oxide nanoparticles released ions while they
were incorporated into different resin formulations (i.e., heat-cured acrylic resin denture,
chemically cured soft liner, and cream-type adhesive). This ion release could be controlled
and utilized in therapeutic drug delivery for the treatment of oral diseases. However, the re-
lease of these ions may vary. A study showed that the denture base and adhesive had higher
releases compared with the denture liner [
]. Researchers may explore the controlled and
optimum therapeutic release of copper ions for an optimum clinical outcome. A study re-
ported copper-doped mesoporous bioactive glass nanosphere-incorporated resin exhibited
antimicrobial properties, mechanical properties, and a better aging resistance effect [
]. An
etch-and-rinse adhesive with copper nanoparticles appeared to have antimicrobial activity
and prevented the degradation of the adhesive interface without altering the mechanical
properties [
]. Polyacrylic acid-coated copper iodide nanoparticles in another study acted
as an antibacterial additive to adhesive, and their bonding strength or biocompatibility was
not affected [
]. Another study showed that copper nanoparticles added to an adhesive
improved the shear bond strength and antibacterial properties without cytotoxicity [121].
3.3. Copper Nanoparticles in Dental Cements
in vitro
studies showed that copper cements developed compressive strength,
solubility, and antibacterial activity, and they were recommended for use as cariostatic
lining under a less soluble restorative material [
]. Some studies also revealed that
copper in restorative materials reduced microorganisms’ growth and viability [
] and
improved the bond on the teeth interface [
]. Moreover, fluoridated amalgam demon-
strated better caries prevention in both primary and secondary caries adjacent to the
restoration [
]. A study reported photo-polymerized copper(I)-catalyzed azide-alkyne
cycloaddition composites to be mechanically strong and highly tough materials. In addition,
they reduced shrinkage stress and generated a modest exothermic reaction [
]. Another
study showed that copper nanoparticles added to a commercial glass ionomer developed
antibacterial activity against oral strains [
]. On the other hand, blue calcium phosphate
cement with copper ions in another study showed a synergized dual antibacterial effect
and cytocompatibility [
]. Many studies have shown that calcium phosphate cement
with copper phosphate nanoparticles could promote vascularized new bone formation
around cancerous bone defects [
]. On the other hand, a copper-modified zinc oxide
phosphate cement showed low surface allocations of copper but no improvement in its
antimicrobial properties [
]. Therefore, with this limited study, it is difficult to justify the
clinical application. In light of this, the optimization of copper use in restorative materials
Nanomaterials 2022,12, 805 7 of 15
for clinical applications should be investigated further in relation to the various strains
associated with prosthesis-induced oral infection.
3.4. Copper Nanoparticles in Miscellaneous Dental Materials
Copper is the third-most abundant trace element in the human body [
]. Some
reports stated that the lack of copper had a negative influence on immune cells (i.e.,
neutrophils, macrophages, T cells, and natural killer cells), decreased interleukin-2 produc-
tion, and alternately enhanced proinflammatory cytokine production (e.g., tumor necrosis
, and matrix metalloproteinase-2 and -9), which degraded the collagen and ex-
tracellular matrix components in the periodontal ligament [
]. Because copper acts as
a cofactor for metalloenzyme (i.e., superoxide dismutase), which is an essential antioxi-
dant for chronic periodontitis, an optimal level of copper is essential for the prevention of
inflammatory passages [93].
Copper is essential for the development of connective tissue. The elevation of serum
copper has reflected the changes occurring in the periodontal collagen metabolism of
periodontitis patients [
]. A study reported an improvement in chronic periodontitis
in diabetic and non-diabetic patients using increased copper ions levels at baseline for
nonsurgical periodontal therapy [
]. Several studies have also reported increased copper
ion levels in patients suffering from chronic and aggressive periodontitis, as well as in acute
and chronic gingivitis [
]. A study reported a link between the salivary copper ion
level and periodontitis [
]. However, the exact mechanism of the increase in copper in the
plasma and its association with periodontal disease is still unclear and needs to be identified.
Some studies showed the therapeutic application of copper nanoparticles for periodontal
therapy. They demonstrated that copper-nanoparticle-based antimicrobial ions inhibited
bacterial growth. They also observed the controlled and sustained release of bactericidal
copper concentrations for localized periodontal therapy [
]. Furthermore, some studies
used copper-nanoparticle-containing composite materials for periodontal therapy. They
used a sodium copper chlorophyllin solution to reduce the production of volatile sulfur
compounds by inhibiting the periodontal anaerobes associated with malodour, and they
recommended using it to improve oral and periodontal health [101].
Another study used copper-calcium hydroxide nanoparticles for treating apical pe-
riodontitis in an endodontically treated tooth, and it recommended using them to treat
periodontitis [
]. Researchers have used several copper nanoparticle formulations for
periodontal therapy. However, these nanoparticle formulations are still limited in labora-
tory research, and their effects in clinical applications remain unclear. Further dedicated
research may improve the use of copper nanoparticles in antimicrobial, anti-inflammatory,
and regenerative periodontal therapy.
Endodontic treatment mostly fails due to microbial infections. The inadequate disin-
fection of root canals is a main cause of post-treatment reinfection [
]. Studies showed
that bacteria can survive inside the root canal after a careful chemo-mechanical prepara-
tion [
]. Copper nanoparticles, due to their ionic compounds, have demonstrated the
potential to produce and capture electrons, as well as to generate radical oxygen species.
These particles have led to toxic hydroxyl radical production and constitute an antimi-
crobial agent in endodontic treatment [
]. On the other hand, copper nanowires
have shown excellent antimicrobial effects against the oral microbes associated with the en-
dodontic systems, so it is suggested that they be considered for root canal disinfection [
Moreover, a study explained the antibacterial effect of copper sulfate nanoparticles and
proposed further clinical trials for clinical settings [
]. Biofilm is resistant to common
intracanal irrigation, antimicrobial drugs, and the host immune response. A study reported
that in such cases, copper hydroxide nanoparticle–based endodontic paste can reduce the
growth and replication time of root canal system–associated oral microbes, which affects the
formation and persistence of biofilm. The researchers suggested using copper hydroxide
nanoparticle–based endodontic paste for the prevention and treatment of biofilm-associated
endodontic infections [107].
Nanomaterials 2022,12, 805 8 of 15
With the progress of multifunctional biomaterials in bone grafting, the possibility
of osteogenesis and angiogenesis has attracted attention in bone and tissue regeneration
research. Inspired by the antibacterial activity of copper ions, a study reported develop-
ing a copper-nanoparticle-based nonstoichiometric dicalcium silicate for infectious bone
repair [
]. Another study reported that a copper-doped biphasic calcium phosphate
powder that was made of hydroxyapatite and
-tricalcium phosphate powder exhibited
antibacterial activity. In addition, they reported that it had good adherence to bone marrow
cells and maintained good cell viability. Therefore, they recommended it as a promising bio-
ceramic for bone substitution and/or prosthesis coatings [
]. A study reported using
graphene oxide copper nanocomposites for bone regeneration and revealed vascularized
new bone formation [
]. Although studies are limited in this field, they are promising.
Clinical studies using copper nanoparticles in various tissue engineering strategies may
result in a new direction of regenerative biomaterials.
4. Biocompatibility Studies of Copper Nanoparticles
The biocompatibility of nanoparticles is an important concern these days. The rapid
growth of nanotechnology is rampant in every research field, including biomedical research.
However, to date, no authentic information exists on the inferences of nanoparticles on
human health [
]. Copper is a necessary trace element, and its deficiency is conducive to
various diseases in humans. In addition, it acts as a catalyst cofactor in some redox enzymes
that are essential for broad-spectrum metabolic processes. On the other hand, if the copper
intake exceeds the tolerable limit, it shows toxic effects that lead to cell death [
]. Despite
the great potential of the biomedical application of copper nanoparticles, toxicity studies of
these nanoparticles are mostly confined to in vitro studies.
Copper nanoparticles have shown toxic effects on several cell lines [
]. Several
in vitro
studies have been conducted. However, only a few studies reported the
in vivo
toxicity of copper nanoparticles [
]. No information was provided on the bioavail-
ability and excretion data of long-term exposure to copper nanoparticles. Future research is
needed to provide a detailed and systematic overview of both the
in vitro
and the
in vivo
toxicity of copper nanoparticles, as well as their kinetics. Recently, the preliminary inves-
tigation of the biocompatibility of copper nanoparticles showed that they have toxicity
in both humans and the environment [
]. Even though copper is sustained in the
homeostasis of the human body, excess copper showed toxic effects on the kidney and
liver [
]. Although the possible risks of copper nanoparticles have been identified in
human health, their subacute toxicity has not yet been defined.
Copper nanoparticles that are 23.5 nm in size are considered to be class 3 medium toxic
materials, with an LD50 value of 413 mg/kg of body weight. Copper nanoparticles’ toxicity
is related to their ionization [
]. Copper nanoparticles lead to ultra-high reactiveness
due to their large surface and active functional ions. They react with hydrogen ions in the
gastric juice and produce a large amount of hydrogen carbonate, and their excretion leads
to kidney disorders. In addition, a study showed that the toxicity of copper nanoparticles
depends on gender. Male mice showed more severe toxic symptoms than females after
being exposed to the same mass of nanoparticles [138]. Another study also identified that
the increased production of reactive oxygen species and reactive nitrogen species plays an
important role in copper nanoparticle-induced organ impairment [144].
The interaction and impact of nanoparticles on cells and tissues have been explained
differently based on their distribution, particle size, and penetration capacity. Studies have
also reported that the variation of the effects depends on the different synthesis methods
of nanoparticles [
]. Therefore, with this limited study, it is difficult to bring a gross
scenario. The effect and involvement of nanoparticles should be clearly defined. Thus,
detailed studies focusing on their toxicity, bioavailability, kinetics, and biodistribution
in different organs, including the liver, brain, lung, heart, and spleen, should be further
investigated. Although, some studies described the potentials of copper and other metallic
nanoparticles in specific or different aspects of dental applications, the biosafety was not
Nanomaterials 2022,12, 805 9 of 15
clearly identified [
]. At the same time, the synthesis, the morphological and physic-
ochemical properties of copper nanoparticles, and these properties’ impacts also need to be
explored. Hence, concrete information regarding copper nanoparticles’ biocompatibility
will be in the frame for their future applications.
5. Conclusions
Copper nanoparticles play a dual role in the development of the properties of dental
materials. The inclusion of copper nanoparticles may improve the physio-mechanical
properties and introduce or enhance the antimicrobial activities of various dental materials.
It is expected that researchers and clinicians will focus on the perspective of cost-effective
copper nanoparticles in dentistry. This will reveal potentials and limitations, as well as
open a new door to dental biomaterials research for the use of copper nanoparticles in
clinical dental practice.
Author Contributions:
V.W.X. and M.Z.I.N. equally conceived the conceptual design, interpretation,
and writing—original draft preparation; I.X.Y. and C.Y.K.L. critically commented; and M.Z.I.N.,
O.Y.Y., and C.H.C. revised the draft. All authors have read and agreed to the published version of
the manuscript.
This review was funded by the National Natural Science Foundation of China (NSFC)
General Program 81870812.
Conflicts of Interest: The authors declare no conflict of interest.
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... Dental bonding materials come into direct contact with teeth but are Table 1 List of some nanoparticles antimicrobial activity in dentistry [26]. ...
... List of some Copper nanoparticles application in dental Implant [26]. ...
... The HA NPs can be used to cure bone problems [84]. Table 3 List of some Titanium nanoparticles application in dental Implant [26]. Table 4 List of some Zinc nanoparticles application in dental Implant [26]. ...
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Nanoparticles have huge scope in the research field of dentistry and also have a wide area of application. This review paper focused on the different types of applications of nanoparticles in dentistry, which kinds of nano-particles show good antimicrobial properties, biocompatibility, good physio-mechanical properties, etc. It also focused on how restorative and therapeutic nanoparticles are used in dentistry and helped in dental implants. Different types of nano-coating can be widely used in dentistry for the structural improvement of teeth. More biocompatible materials can be researched and developed to prevent the failure of dental implants, which is a great area of research interest nowadays. Implant failure due to cytotoxicity and biocompatibility is a big challenge in dentistry that can be developed or solved by nanotechnology. The objective of this review paper is, therefore, to give an overview of the principles of nanomaterials and basic research and applications of dental nanomaterials.
... Metallic nanoparticles possess a range of advantages such as broad antibacterial spectrum, high antibacterial activities, good biocompatibilities, durable stabilities and non-resistance. Silver [124][125][126][127], gold [127][128][129], copper oxide [130][131][132], zinc oxide [133][134][135], iron oxide [136][137][138], titanium dioxide [139][140][141], and magnesium oxide nanoparticles [142][143][144] have all been frequently documented as antibacterial substances. The antibacterial mechanism of these nanoparticles is mainly: 1. electrostatic adsorption and influences the bacterial membrane and cell wall function; 2. the destruction of bacterial enzymes, proteins, and DNA structure. ...
... To that end, nanoparticles (NPs) have been incorporated into wound healing devices to inhibit bacterial growth [2,3]. Metallic NPs including MgO [2,4], CuO [5] and Ag [6], have demonstrated potent antibacterial, antifungal and antiviral properties. AgNPs are the most common form of nanomaterials for microcidal effects. ...
... Hydrogen ions in the acidic environment dissolve hydroxyapatite, producing calcium ions, phosphate ions, and water. Therefore, the surface demineralisation of the tooth occurs [97]. After that, the loss of minerals leads to developing permeability and porosity, enamel crystal derangement, and further acid diffusion to enamel pores. ...
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Ceramic nanomaterials are nanoscale inorganic metalloid solids that can be synthesised by heating at high temperatures followed by rapid cooling. Since the first nanoceramics were developed in the 1980s, ceramic nanomaterials have rapidly become one of the core nanomaterials for research because of their versatility in application and use in technology. Researchers are developing ceramic nanomaterials for dental use because ceramic nanoparticles are more stable and cheaper in production than metallic nanoparticles. Ceramic nanomaterials can be used to prevent dental caries because some of them have mineralising properties to promote the remineralisation of tooth tissue. Ceramic minerals facilitate the remineralisation process and maintain an equilibrium in pH levels to maintain tooth integrity. In addition, ceramic nanomaterials have antibacterial properties to inhibit the growth of cariogenic biofilm. Researchers have developed antimicrobial nanoparticles, conjugated ceramic minerals with antibacterial and mineralising properties, to prevent the formation and progression of caries. Common ceramic nanomaterials developed for caries prevention include calcium-based (including hydroxyapatite-based), bioactive glass-based, and silica-based nanoparticles. Calcium-based ceramic nanomaterials can substitute for the lost hydroxyapatite by depositing calcium ions. Bioactive glass-based nanoparticles contain surface-reactive glass that can form apatite crystals resembling bone and tooth tissue and exhibit chemical bonding to the bone and tooth tissue. Silica-based nanoparticles contain silica for collagen infiltration and enhancing heterogeneous mineralisation of the dentin collagen matrix. In summary, ceramic nanomaterials can be used for caries prevention because of their antibacterial and mineralising properties. This study gives an overview of ceramic nanomaterials for the prevention of dental caries.
... Although different kinds of bioactive materials could be used in caries management [15], not many have been developed into clinical applications, due to different problems. For example, using nanoparticles based on metal or metallic oxide for caries management is being extensively researched [16]. However, the toxicity of nanoparticles to mammalian cells concerns researchers [17]. ...
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Objective: Researchers are studying the use of antimicrobial peptides as functional biomaterials to prevent and treat dental caries. This study aims to investigate the global research interest in antimicrobial peptides for caries management. Methods: Two independent investigators systematically searched with keywords (‘Caries’ OR ‘Dental caries’) AND (‘Antimicrobial peptide’ OR ‘AMP’ OR ‘Statherin’ OR ‘Histatin’ OR ‘Defensin’ OR ‘Cathelicidin’) on Web of Science, PubMed and Scopus. They removed duplicate publications and screened the titles and abstracts to identify relevant publications. The included publications were summarized and classified as laboratory studies, clinical trials or reviews. The citation count and citation density of the three publication types were compared using a one-way analysis of variance. The publications’ bibliometric data were analyzed using the Bibliometrix program. Results: This study included 163 publications with 115 laboratory studies (71%), 29 clinical trials (18%) and 19 reviews (11%). The number of publications per year have increased steadily since 2002. The citation densities (mean ± SD) of laboratory study publications (3.67 ± 2.73) and clinical trial publications (2.63 ± 1.85) were less than that of review articles (5.79 ± 1.27) (p = 0.002). The three publication types had no significant difference in citation count (p = 0.54). Most publications (79%, 129/163) reported the development of a novel antimicrobial peptide. China (52/163, 32%) and the US (29/163, 18%) contributed to 50% (81/163) of the publications. Conclusion: This bibliometric analysis identified an increasing trend in global interest in antimicrobial peptides for caries management since 2002. The main research topic was the development of novel antimicrobial peptides. Most publications were laboratory studies, as were the three publications with the highest citation counts. Laboratory studies had high citation counts, whereas reviews had high citation density.
... In contrast, the antimicrobial effect of Cu is due to direct contact with bacteria or viruses, which is a probable reason for lower biofilm formation. Cu alters the permeability of bacterial cell membranes and accumulates in the cell, changing biochemical processes by interacting with cell enzymes and DNA and causing cell death [53]. Information on the adhesion of bacteria to the surface of a composite and biofilm formation is more meaningful information for the prevention of secondary caries. ...
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Experimental dental resin composites containing copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were developed to impart anti-bacterial properties. Increasing amounts of Cu-MBGN (0, 1, 5 and 10 wt%) were added to the BisGMA/TEGDMA resin matrix containing micro- and nano-fillers of inert glass, keeping the resin/filler ratio constant. Surface micromorphology and elemental analysis were performed to evaluate the homogeneous dis-tribution of filler particles. The study investigated the effects of Cu-MBGN on the degree of conversion, polymerization shrinkage, porosity, ion release and anti-bacterial activity on S. mu-tans and A. naeslundii. Experimental materials containing Cu-MBGN showed a dose-dependent Cu release with an initial burst and a further increase after 28 days. The composite containing 10% Cu-MBGN had the best anti-bacterial effect on S. mutans, as evidenced by the lowest adher-ence of free-floating bacteria and biofilm formation. In contrast, the 45S5-containing materials had the highest S. mutans adherence. Ca release was highest in the bioactive control containing 15% 45S5, which correlated with the highest number of open porosities on the surface. Polymer-ization shrinkage was similar for all tested materials, ranging from 3.8 to 4.2%, while the degree of conversion was lower for Cu-MBGN materials. Cu-MBGN composites showed better an-ti-bacterial properties than composites with 45S5 BG.
... Due to their expensive reagents and the environmental hazards associated with CuO NPs (nanoparticles), synthesis and preparation have become major challenges for scientists. Xu et al. [21] explored the applications of CuO nanoparticles in dentistry. Akintelu et al. [22] successfully demonstrated the synthesis of CuO NP at low cost. ...
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In this study, we synthesized a reduced form of graphene oxide/copper oxide (rGO/CuO) nanocompounds produced at rGO wt. of 0.125%, 0.25%, 0.5% and 1%. The crystallinity indexes for rGO and rGO/CuO increased, and that for CuO decreased as the test temperatures increases, while the crystallinity indexes of rGO, CuO and rGO/CuO decreases with test periods increment. Measurement by dynamic light scattering reported average crystallite sizes of 0.7, 8.8, 25.4, 38.5 nm for 0.125 wt.% rGO/CuO, 0.25 wt.% rGO/CuO, 0.50 wt.% rGO/CuO and 1.0 wt.% rGO/CuO respectively. The electrochemical properties of the nanocomposites were checked. The rGO/CuO XRD peaks were 18.114320 Å, 225.1856 Å, 321.41740 Å, and 365.98290 Å, with 11.051640%, 0.461075%, 0.280083%, and 0.174259% for 2ϴ of 22.2031°, 43.5865°, 50.7050°, and 74.3729°, respectively. FTIR spectroscopy identified the existence of vibrational frequencies with pseudo-capacitance at 458 cm−1 which confirmed the presence of rGO-CuO nanoparticles. The voltammetry of rGO-CuO indicated the increment of electrochemical activity, large capacitance, and conduction in the reduced rGO/CuO composite. For rGO wt. of 0.125%, 0.25%, 0.5%, and 1.0%, the rGO/CuO composite specific capacitance was 561 F/g, 582 F/g, 597 F/g, and 611 F/g, respectively, which indicated good electrochemical performance.
... CuNPs are extensively used in electronics and metallic inks due to their optical, electrical, catalytic, and antimicrobial properties [7][8][9] . CuNPs have various applications, which increase, in turn, their environmental exposure [10,11] . Therefore, the bioaccumulation and toxicity of CuNPs have been reported in plants [12] and animals such as rainbow trout (Oncorhynchus mykiss), zebrafish (Danio rerio) [13] , nematode (Caenorhabditis elegans), algae, daphnia [14] , and Drosophila melanogaster [15] . ...
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Copper nanoparticles (CuNPs) are used in a range of industries such as semiconductors, catalysts, sensors, and antimicrobial agents. While there are already studies on its possible genotoxicity, few of these reports evidence in vivo. Copper nanoparticles (CuNPs) were prepared via chemical reduction and characterized by electronic transmission microscopy (TEM) and X-ray diffraction. Drosophila melanogaster (D. melanogaster) were reared on CuNPs, and Cu +2 (as CuSO4) treated food from egg to egg stage. The total number of progeny, percentage of aberrant phenotypes, oxidative stress, and gene expression of heat shock protein-70 (Hsp70) and superoxide dismutase 2 (Sod2) were investigated. Results showed that the acute exposure of CuNPs did not affect the fly's survivorship, unlike Cu +2, which showed higher toxicity. Chronic exposure of D. melanogaster to CuNPs (100 ppm) and Cu +2 (50 and 100 ppm) resulted in a delay in the development of three consecutive generations. Furthermore, the ingestion of Cu +2 and CuNPs during early developmental stages caused a dose-dependent reduction in the number of emerged flies. CuNPs and Cu +2 treatments resulted in distinctive phenotypic aberrations, such as deformed wings transmitted to the offspring in subsequent generations. Finally, CuNPs and Cu +2 treatments caused downregulation of the Sod2 gene and upregulation of the Hsp70 gene in the second and third generations. This study indicated that CuNPs are mutagenic for D. melanogaster. So, it is necessary to evaluate CuNPs toxicity to reduce human health-related issues.
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Researchers have developed novel bioactive materials for caries management. Many clinicians also favour these materials, which fit their contemporary practice philosophy of using the medical model of caries management and minimally invasive dentistry. Although there is no consensus on the definition of bioactive materials, bioactive materials in cariology are generally considered to be those that can form hydroxyapatite crystals on the tooth surface. Common bioactive materials include fluoride-based materials, calcium- and phosphate-based materials, graphene-based materials, metal and metal-oxide nanomaterials and peptide-based materials. Silver diamine fluoride (SDF) is a fluoride-based material containing silver; silver is antibacterial and fluoride promotes remineralisation. Casein phosphopeptide-amorphous calcium phosphate is a calcium- and phosphate-based material that can be added to toothpaste and chewing gum for caries prevention. Researchers use graphene-based materials and metal or metal-oxide nanomaterials as anticaries agents. Graphene-based materials, such as graphene oxide-silver, have antibacterial and mineralising properties. Metal and metal-oxide nanomaterials, such as silver and copper oxide, are antimicrobial. Incorporating mineralising materials could introduce remineralising properties to metallic nanoparticles. Researchers have also developed antimicrobial peptides with mineralising properties for caries prevention. The purpose of this literature review is to provide an overview of current bioactive materials for caries management.
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Vat photopolymerization (VPP) is an additive manufacturing process commonly used in medical applications. This work aims, for the first time in the literature, to extend and enhance the performance of a commercial medical-grade resin for the VPP process, with the development of nanocomposites, using Copper (Cu) nanoparticles as the additive at two different concentrations. The addition of the Cu nanoparticles was expected to enhance the mechanical properties of the resin and to enable biocidal properties on the nanocomposites since Cu is known for its antibacterial performance. The effect of the Cu concentration was investigated. The nanocomposites were prepared with high-shear stirring. Specimens were 3D printed following international standards for mechanical testing. Their thermal and spectroscopic response was also investigated. The morphological characteristics were examined. The antibacterial performance was evaluated with an agar well diffusion screening process. The experimental results were analyzed with statistical modeling tools with two control parameters (three levels each) and eleven response parameters. Cu enhanced the mechanical properties in all cases studied. 0.5 wt.% Cu nanocomposite showed the highest improvement (approximately 11% in tensile and 10% in flexural strength). The antibacterial performance was sufficient against S. aureus and marginal against E. coli.
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Nanoparticles based on metal and metallic oxide have become a novel trend for dental use as they interfere with bacterial metabolism and prevent biofilm formation. Metal and metal oxide nanoparticles demonstrate significant antimicrobial activity by metal ion release, oxidative stress induction and non-oxidative mechanisms. Silver, zinc, titanium, copper, and magnesium ions have been used to develop metal and metal oxide nanoparticles. In addition, fluoride has been used to functionalise the metal and metal oxide nanoparticles. The fluoride-functionalised nanoparticles show fluoride-releasing properties that enhance apatite formation, promote remineralisation, and inhibit demineralisation of enamel and dentine. The particles’ nanoscopic size increases their surface-to-volume ratio and bioavailability. The increased surface area facilitates their mechanical bond with tooth tissue. Therefore, metal and metal oxide nanoparticles have been incorporated in dental materials to strengthen the mechanical properties of the materials and to prevent caries development. Another advantage of metal and metal oxide nanoparticles is their easily scalable production. The aim of this study is to provide an overview of the use of metal and metal oxide nanoparticles in caries prevention. The study reviews their effects on dental materials regarding antibacterial, remineralising, aesthetic, and mechanical properties.
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This work was focused on study of anti-infection ability and its underlying mechanism of a novel dental implant made of titanium-copper (TiCu) alloy. In general, most studies on antibacterial implants have used a single pathogen to test their anti-infection ability using infectious animal models. However, dental implant-associated infections are polymicrobial diseases. We innovatively combine the classic ligature model in dogs with sucrose-rich diets to induce oral infections via the canine native oral bacteria. The anti-infection ability, biocompatibility and underlying mechanism of TiCu implant were systematically investigated in comparison with pure Ti implant via general inspection, hematology, imageology (micro-CT), microbiology (16S rDNA and metagenome), histology, and Cu ion detections. Compared with Ti implant, TiCu implant demonstrated remarkable anti-infection potentials with excellent biocompatibility. Additionally, the underlying anti-infection mechanism of TiCu implant was considered to involve maintaining the oral microbiota homeostasis. It was found that the carbohydrates in the plaques formed on the surface of TiCu implant were metabolized through the tricarboxylic acid cycle (TCA) cycles, which prevented the formation of an acidic microenvironment and inhibited the accumulation of acidogens and pathogens, thereby maintaining the microflora balance between aerobic and anaerobic bacteria.
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Experimental dental resin composites incorporating copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were designed to impart antibacterial and remineralizing properties. The study evaluated the influence of Cu-MBGN on the mechanical properties and photopolymerization of resin composites. Cu-MBGN were synthesized using a microemulsion-assisted sol–gel method. Increasing amounts of Cu-MBGN (0, 1, 5, and 10 wt %) were added to the organic polymer matrix with inert glass micro- and nanofillers while maintaining a constant resin/filler ratio. Six tests were performed: X-ray diffraction, scanning electron microscopy, flexural strength (FS), flexural modulus (FM), Vickers microhardness (MH), and degree of conversion (DC). FS and MH of Cu-MBGN composites with silica fillers showed no deterioration with aging, with statistically similar results at 1 and 28 days. FM was not influenced by the addition of Cu-MBGN but was reduced for all tested materials after 28 days. The specimens with 1 and 5% Cu-MBGN had the highest FS, FM, MH, and DC values at 28 days, while controls with 45S5 bioactive glass had the lowest FM, FS, and MH. DC was high for all materials (83.7–93.0%). Cu-MBGN composites with silica have a potential for clinical implementation due to high DC and good mechanical properties with adequate resistance to aging.
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Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates (x = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in Ca10Cu x (PO4)6(OH)2-2xO2x). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and E. coli, releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against P. aeruginosa. This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu2+ were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.
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The constant advent of major health threats such as antibacterial resistance or highly communicable viruses, together with a declining antimicrobial discovery, urgently requires the exploration of innovative therapeutic approaches. Nowadays, strategies based on metal nanoparticle technology have demonstrated interesting outcomes due to their intrinsic features. In this scenario, there is an emerging and growing interest in copper-based nanoparticles (CuNPs). Indeed, in their pure metallic form, as oxides, or in combination with sulfur, CuNPs have peculiar behaviors that result in effective antimicrobial activity associated with the stimulation of essential body functions. Here, we present a critical review on the state of the art regarding the in vitro and in vivo evaluations of the antimicrobial activity of CuNPs together with absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments. Considering the potentiality of CuNPs in antimicrobial treatments, within this Review we encounter the need to summarize the behaviors of CuNPs and provide the expected perspectives on their contributions to infectious and communicable disease management.
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Endodontic failure has been and continues to be a problem for endodontics-specialists. Complicated anatomy, numerous foramens, and accessory canals are an environment for microor- ganisms to infect the teeth. The purpose of the present work was to evaluate the regeneration of copper–calcium hydroxide (Cupral)-endodontically treated teeth diagnosed with apical periodontitis using an electrophoresis technique. In total, 132 patients, aging from 19 to 65 years old, underwent endodontic treatment mono- and multi-radicular teeth, with complicated canals from January 2019 to June 2020. The patients were divided into two groups: (i) the control group—which included 54 patients (n = 62 teeth) receiving endodontic paste (Calcipast + 1) and, as final filling, the AH- PlusTM cement—and (ii) the Cupral group, which included 78 patients (n = 80 teeth) receiving Cupral paste plus the electrophoretic current and, as final filling, the Atacamit-alkaline cement. The clinical cases were periodically observed along an 18-month follow-up period via radiography. Data were expressed as focal size of the lesions (mean ± standard error (SEM) of all the radiographic outcomes) observed in each group at each interval point. Statistical analysis was performed using the Student’s t-test that allowed us to compare the control and Cupral groups; the statistical significance was set at p < 0.05 and p < 0.01, where the latter was highly significant. Before treatments, the focal sizes were 4.8 mm and 4.95 mm for control and Cupral-treated groups, respectively. After 6 months, the mean focal sizes were 3.9 mm and 2.14 mm for the control and Cupral groups, respectively. After 12 months, in the control group, the mean focal size was measured at 2.8 mm, while, in Cupral group, the lesion size decreased down to 0.31 mm and a highly dynamic regeneration of the destructive focal-bone occurred. After 18 months, the lesions were further significantly reduced in the control group (mean values of 2.62 mm), while they were barely detectable in the Cupral group (0.2 mm). In conclusion, we provide initial evidence that the Cupral-electrophoresis methodology is effective in treating destructive periodontitis of teeth with problematic canals up to 18 months, thus allowing teeth preservation.
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Background. The incorporation of an antibacterial agent into an adhesive could improve its clinical performance. Some nanoparticles (NPs), including copper nanoparticles (Cu NPs), display an antibacterial effect. Therefore, Cu NPs could act as a nanofiller when added to an adhesive. Objectives. The aim of this study was to evaluate the antibacterial activity, cytotoxicity, and shear bond strength (SBS) of an experimental dental adhesive with Cu NPs. Material and methods. Different concentrations (0.0050 wt%, 0.0075 wt% and 0.0100 wt%) of Cu NPs were added to the adhesive. The distribution of Cu NPs in the polymer matrix was observed based on transmission electron microscope (TEM) images. The antimicrobial activity of the adhesive + Cu NPs was evaluated with the agar disk diffusion test against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Streptococcus mutans (S. mutans). The cytotoxicity assay was performed by means of the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method with human pulp cells (HPC). Additionally, the SBS tests were carried out (n = 31) and the modes of fracture were registered. The vestibular and lingual surfaces of each tooth were randomly assigned to the study groups (group I – control adhesive; group II – adhesive + 0.0100 wt% Cu NPs). The samples were statistically analyzed (p ≤ 0.05). Results. The adhesive + 0.0100 wt% Cu NPs showed inhibition zones against the strains under study that were similar to, or slightly smaller than, the halos produced by chlorhexidine (CHX) and specific drugs for each strain (30 μg of cefotaxime against S. mutans and S. aureus, and 1.25/3.75 μg of sulfamethoxazole/trimethoprim against E. coli). The control adhesive was moderately cytotoxic (relative cell viability of 36.7 ±0.8%), being more cytotoxic than Cu NPs themselves (58.3 ±0.1%). A significantly higher SBS was obtained for the adhesive + 0.0100 wt% Cu NPs (6.038 ±2.95 MPa) than for the control group (3.278 ±1.75 MPa). The modes of fracture in group I were almost equally distributed between adhesive and cohesive failures whereas in group II, the failure was mainly cohesive.
The antimicrobial activity of copper nanoparticles (CuNps) has been studied against different pathogenic microorganisms, however to our knowledge, no studies have been reported about their activity against periodontal bacteria in a biofilm. Therefore, in order to bridge this information gap, this study aims to observe and count the formation of oral biofilm on titanium alloys coated with different types of CuNps. Three different methods were used to synthetize and then apply a coating of CuNps on dental implant healing caps, by then, their antibacterial properties were investigated using an in vitro oral biofilm by plate count method and confocal laser microscopy. The result of the counts, showed that the lower microbial load is observed in the caps coated with CuNps obtained by copper electroplating, it can be concluded, within the limitations of this study, that CuNps obtained by copper electroplating showed greater bactericidal effect that PVD methods, especially in periodontal pathogenic bacteria like P.gingivalis, and P. intermedia. More studies are necessary for corroborate this observation and better understand the reason why only CuNps obtained by certain methods were more bactericidal tan others and the reason why only some bacteria were affected. The antimicrobial properties exhibited by CuNps could be useful for develop anti-infective biomaterials become a strategy to control dental biofilm.
Bacteria-associated infection and poor osseointegration are two main reasons for orthopedic implant failure. Ti-Cu alloy exhibited excellent antibacterial property, but still presented unsatisfied osteogenic activities. Therefore, Ti-Cu alloy was surface modified by an alkali-heat treatment in this paper to improve the osteogenic ability without reduction in antibacterial ability. A TiO2/CuO/Cu2O composite coating with nanostructure was deposited on Ti-Cu alloy. The coating showed increased roughness and great hydrophilicity. Antibacterial tests indicated that the modified Ti-Cu alloy exhibited stronger antibacterial ability against Staphylococcus aureus (S. aureus) than Ti-Cu alloy. Meanwhile, cell experiments demonstrated that the composite coating promoted initial adhesion and spreading of MC3T3-E1 cells, enhanced alkaline phosphatase (ALP) activities as well as extracellular matrix (ECM) mineralization, and significantly upregulated osteogenesis-related gene expressions. It was suggested that the nano-structured TiO2/CuO/Cu2O coating on Ti-Cu alloy might provide a potential strategy for orthopedic implant failure.
Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are the most typical pathogenic bacteria with a significantly high risk of bio-contamination, widely existing in hospital and public places. Recent studies on antibacterial materials and the related mechanisms have attracted more interests of researchers. However, the antibacterial behavior of materials is usually evaluated separately on the single bacterial strain, which is far from the practical condition. Actually, the interaction between the polymicrobial communities can promote the growing profile of bacteria, which may weaken the antibacterial effect of materials. In this work, a 420 copper-bearing martensitic stainless steel (420CuSS) was studied with respect to its antibacterial activity and the underlying mechanism in a co-culturing infection model using both E. coli and S. aureus. Observed via plating and counting colony forming units (CFU), Cu releasing, and material characterization, 420CuSS was proved to present excellent antibacterial performance against the mixed bacteria with an approximately 99.4 % of antibacterial rate. In addition, 420CuSS could effectively inhibit the biofilm formation on its surfaces, resulting from a synergistic antibacterial effect of Cu ions, Fe ions, reactive oxygen species (ROS), and proton consumption of bacteria.