RECENT ADVANCES IN METAL NANOPARTICLES TO TREAT

PERIODONTITIS
Nasiri K, Masoumi SM, Amini S, Goudarzi M, Tafreshi SM, Bagheri A, Yasamineh S, Alwan
M
Arellano MTC, Gholizadeh O.

J Nanobiotechnology

MODERATOR : Dr Parimala
1

PRESENTER: Anitha TR
 INTRODUCTION
2
• The gradual deterioration of the supporting periodontal tissues caused by periodontitis, is thought to be triggered by the colonization
of dysbiotic plaque biofilms in a vulnerable host.
• One of the most prevalent dental conditions in the world, is now the leading factor in adult tooth loss.
• Numerous studies have shown that non-surgical treatment significantly improves clinical and microbiological indices in individuals
with periodontitis.
• Periodontitis has been treated with local or systemic antibiotics as well as scaling and root planning.
• Since there aren't many brand-new antibiotics on the market, several researchers are currently concentrating on creating alternate
methods of combating periodontal germs.
• The most promising of them are Metal NPs since they have potent antibacterial action.
• Metal NPs may be employed as efficient growth inhibitors in a variety of bacteria, making them useful for the treatment of
periodontitis.
• In this way, the new metal NPs contributed significantly to the development of efficient anti-inflammatory and antibacterial platforms
for the treatment of periodontitis. .
 METAL NANOPARTICLES IN PERIODONTICS
•Metal and metal oxide NPs (e.g., Au, Ag, CuO, ZnO) have demonstrated significant antibacterial properties.
•They are effective against a wide range of Gram-negative and Gram-positive bacteria, including drug-resistant strains.
Mechanism of Action:
•The primary antibacterial effect of NPs is due to the generation of reactive oxygen species (ROS), which can degrade DNA, RNA, and proteins
in microbes.
•ZnO NPs, for example, show enhanced antibacterial efficacy due to their strong photocatalytic activities, especially under UV light.
•Metal NPs can disrupt biofilms, which contribute to drug-resistant bacteria and complicate treatment.
•This disruption is vital in combating the resurgence of drug-resistant infections.
Metal Ions and Bacterial Interaction:
•Metal ions released by NPs interact with negatively charged bacterial
3 membranes, allowing ions to enter cells.
•Inside the cell, these ions inhibit protein and nucleic acid production by reacting with sulfhydryl groups on microbial proteins.
Size and Surface Charge:
•The antibacterial efficacy of NPs is influenced by their size and surface charge.
•Smaller particles with a higher surface-to-volume ratio tend to have stronger antibacterial effects without degrading the material's
mechanical properties
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GOLD NANOPARTICLES
Size and Structure
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. nanoparticles (AuNPs) typically have a diameter between 50 and 150 nm.
- Gold
- They serve as drug carriers with excellent bioavailability and functionality.
Photothermal Treatment
- AuNPs are used in photothermal treatment, which involves using specific wavelengths of light to convert light into heat.
- This heat generation leads to protein degradation, making AuNPs effective for treating dental problems.
Antibacterial and Antifungal Properties:
- AuNPs are effective antibacterial agents that perform well against various infections.
- They also possess antifungal properties, enhancing their utility in various medical applications.
Applications in Dentistry:
- AuNPs have been used in dental caries treatment, gum disease management, tissue engineering, dental implantology, and even
cancer diagnostics.
- When added to other biomaterials, AuNPs enhance the antibacterial and antifungal properties of these materials.
Use as Biomaterial Fillers:
- Due to their beneficial properties, AuNPs are popular as fillers in biomaterials, enhancing both their therapeutic and mechanical
capabilities.
Gold Nanoparticles (Aunps) In Treating Periodontitis
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Therapeutic Role of 45 nm AuNPs in Periodontal Inflammation and Tissue Regeneration
Reduction of Inflammation
- 45 nm AuNPs significantly reduce inflammation in periodontal tissues.
- Controls the production of both pro-inflammatory and anti-inflammatory cytokines.
- Regulates macrophage polarization, affecting human periodontal ligament cell (hPDLC) differentiation.
Enhancement of Tissue Differentiation
- Interaction between AuNP-conditioned macrophages and AuNP-stimulated hPDLCs enhances periodontal tissue differentiation.
- Particularly evident in LPS-activated inflammatory macrophage-hPDLC coculture systems.
- Shows direct positive effects of AuNPs on hPDLCs, apart from macrophage interaction.
- Significant increase in new periodontal attachment, bone, and cementum formation in periodontal defects.
Modulation of Early Inflammatory Response
- AuNPs modulate macrophage phenotypes during the early inflammatory response.
- Results in decreased inflammatory cytokines and increased reparative cytokines, like BMP-2.
- BMP-2 stimulates PDLC development, and regeneration of periodontal tissues, and halts periodontitis progression.

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SILVER NANOPARTICLES 7
• Composition and Size:
• - Silver nanoparticles (AgNPs) are made from pure crystalline silver, ranging in size from 1 to 100 nm.
• - They possess distinct physicochemical properties such as smaller particle size, larger surface area, and quantum confinement
effects.
Antibacterial and Antifungal Properties:
• - AgNPs can prevent bacteria from producing oxides, making them effective in blocking bacterial metabolism.
• - These properties have made AgNPs popular for oral infection prophylaxis, disinfection, and prevention in dentistry
Applications in Dentistry:
• - AgNPs are used in various dental fields, including implantology, prosthodontics, endodontics, restorative dentistry, orthodontics
• , and periodontics.
• - They are effective in removing plaque, tartar, and bacterial and fungal infections in the mouth
• A g+ exchanged zeolites in dental adhesives significantly reduced early bacterial attachment, biomass, biofilm formation, and
metabolic activity.
• A nearly 2-order-of-magnitude decrease in biofilm colony-forming units (CFU) was observed for cariogenic pathogens such as
Streptococcus mutans, and S. sanguinis.
 Silver Nanoparticles In Periodontitis Treatment

Biosynthesis of AgNPs: 8
• Researchers used Oroxylum indicum stem bark extracts as a reducing agent to biosynthesize AgNPs (OI/AgNPs).
•The biosynthesized OI/AgNPs were stable, spherical nanoparticles with a size range of approximately 21.49 nm
Effects on hPDLSCs:
•OI/AgNPs accumulated in the cytoplasm of human periodontal ligament stem cells (hPDLSCs) with high cell viability.
•They reduced IL-1β secretion from LPS-stimulated hPDLSCs and promoted cell proliferation in H₂O₂-treated hPDLSCs.
• It increased ALP activity and calcium content in hPDLSCs, promoting osteoblastic development.
•The biosynthesized OI/AgNPs were non-cytotoxic, protected hPDLSCs from oxidative stress and inflammation, and showed potential for
regenerative therapy in peri-implantitis.
Ulvan-based AgNP System:
•AgNPs were biosynthesized using Ulvan, a polysaccharide isolated from Ulva lactuca, for use in a new mouthwash formulation.
•This mouthwash demonstrated strong antibacterial efficacy against Lactobacillus, Candida albicans, Streptococcus mutans, and
Staphylococcus aureus at a concentration of 100 μL/mL, showing promise as an oral antibacterial agent.
AgNPs Against P. gingivalis:
•AgNPs were biosynthesized using the endophytic fungus Fusarium semitectum and characterized through various methods.
•The AgNPs demonstrated antibacterial effectiveness against the periodontal pathogen Porphyromonas gingivalis .
Combination with CHX and Hydrogels:
•AgNPs can be combined with chlorhexidine (CHX) for a synergistic antibacterial effect, enhancing periodontal treatment.
•The PerioChip, a CHX digluconate-containing biodegradable gelatin, has been used for controlled release, and polymer
hydrogels doped with AgNPs have shown antibacterial activity against Escherichia coli and Staphylococcus aureus.
•AgNPs increase bacterial membrane permeability, leading to cell lysis, and damage bacterial DNA, proteins, and lipids.
At low concentrations, they enhance cellular stress without affecting cell differentiation.

Future Applications:
•The development of porous hydrogel-based drug-delivery systems doped with AgNPs could be a significant advancement in the
treatment of periodontal disorders and peri-implantitis. 9

•These systems could serve as scaffolds for tissue regeneration while delivering antibacterial agents locally to the affected areas.
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 ZINC NANOPARTICLES
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Due to their remarkable antibacterial properties, zinc oxide nanoparticles (ZnONPs) are emerging as a potent tool in various
biomedical applications, particularly in dentistry and periodontitis treatment.
Mechanisms of Antibacterial Action:
• It can generate ROS due to its semiconductive nature, which leads to oxidative stress and ultimately damages bacterial cells.
• It can directly interact with bacterial cell walls, causing leakage of cellular contents, and leading to cell death.
• ZnONp release Zn²⁺ ions in aqueous media, which possess inherent antibacterial properties.
Applications in Dentistry:
• They aid in regenerating degraded dentin and treating dentin hypersensitivity, particularly in endodontically treated teeth.
• ZnONPs have been shown to inhibit biofilm formation, which is crucial in preventing bacterial colonization on dental surfaces.
• ZnONPs have been incorporated into various dental materials, such as flowable composite resins and hydrogels, enhancing
their antibacterial properties.
• It as antimicrobial photo-sonosensitizers, can absorb light and ultrasound, leading to ROS production and enhanced
antibacterial activity.
• This approach has been effective against polymicrobial periopathogenic biofilms and has also reduced the expression of
inflammatory cytokines like TNF-α, IL-1β, and IL-6 in human gingival fibroblasts.
Zinc Nanoparticles In Periodontitis Treatment
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Guided Tissue Regeneration (GTR):
• ZnONPs have been added to biodegradable membranes, such as those made of polycaprolactone (PCL), to enhance their antibacterial activity without
compromising osteoblast viability.

• This is particularly important for preventing infections during tissue regeneration in periodontal treatments.

Nanohydrogels:
ZnONPs have been incorporated into hydrogels, such as Mino-ZnO@Alb, which demonstrated:
• broad-spectrum antibacterial activity
• sustained drug release
• and improved tissue repair capabilities
making them promising candidates for periodontal therapy.

Biocompatibility and Safety :

At lower concentrations, ZnONPs exhibit low toxicity while maintaining their antibacterial efficacy.
• ZnONPs have been found to stimulate enzyme activity (e.g., ALT) in saliva, which could be an indicator of periodontal tissue inflammation and degeneration.
Future Research and Clinical Trials:
- While ZnONPs have shown significant potential in vitro, more in vivo studies and clinical trials are necessary to fully understand their efficacy and safety in dental
applications.
TITANIUM DIOXIDE NANOPARTICLES
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General Properties:
• Size: <100 nm
• Distinct surface chemistry and morphology
• High refractive index, chemical stability
Photocatalytic Properties:
• TiO₂ NPs generate free radical oxides and peroxides under light exposure.
• Capable of producing reactive oxygen species (ROS) with strong antibacterial action.
• More effective against Gram-negative bacteria (E. coli, P. aeruginosa) due to their thinner cell walls.
• Less effective against Gram-positive bacteria (S. aureus, Enterococcus faecium) and yeast (C. albicans) due to thicker cell walls.
• TiO₂ NPs are used in ultrasonic irradiation to enhance ROS generation for antimicrobial therapies.

Applications in Periodontal Treatment:

• TiO₂ NPs possess potent bactericidal and sterilizing properties.
• Effective in combating bacteria associated with periodontitis due to their photocatalytic action.
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Innovative Use Of Tio₂-ucns In Antibacterial Photodynamic Therapy (Apdt)

• TiO₂ has a broadband gap energy of 3.2 eV, requiring activation by ultraviolet (UV) light. 14
• However, UV light poses significant risks, such as DNA damage and cell death due to irradiation, limiting the direct use of TiO₂ in some medical

applications.
• To overcome these limitations, Upconversion Nanoparticles (UCNs) have been developed
• UCNs are designed to convert low-energy near-infrared (NIR) light into high-energy UV light via an anti-Stokes emission mechanism, enabling

the activation of TiO₂ without harmful UV exposure

• TiO₂-UCNs demonstrate potent antibacterial activity, particularly against periodontal pathogens like Porphyromonas gingivalis and

Fusobacterium nucleatum.
• In laboratory studies, the colony-forming units (CFU) of bacteria in the light-exposed groups were reduced by four to five orders of magnitude.
• At a medication concentration of 2 mM, almost complete bacterial elimination was observed within 4 hours after an initial 5-minute irradiation

at 2.5 W/cm².
• Antibacterial photodynamic therapy (aPDT) induced by near-infrared light using TiO₂-UCNs represents a promising method for treating

periodontitis.
• This approach allows for targeted bacterial eradication while minimizing damage to surrounding tissues, potentially offering a safer and more

effective treatment option compared to conventional therapies.

MAGNETIC NANOPARTICLES 15
Physicochemical Properties
- Magnetic nanoparticles (MNPs) have gained attention due to their distinct physicochemical features.
- They operate at both the molecular and cellular levels, making them effective for diagnostic and therapeutic applications in dental medicine.
Biofilm Reduction in Dental Composites and Adhesives
MNPs incorporated into dental composites and adhesives help reduce biofilm development, leading to enhanced dental hygiene and reduced
bacterial growth

Structure of Magnetic Nanoparticles

- MNPs are composed of three layers:
- Magnetic iron core
- inner layer of lipophilic fluorescent dye
- Exterior layer of polysaccharide or chitosan matrix
- The majority of MNPs used in biomedical and dental applications are iron oxide nanoparticles (IONPs), specifically:
- Magnetite (Fe3O4)
- Maghemite (γ-Fe2O3)
- Cobalt (Co) and nickel (Ni), despite their high magnetism, are avoided due to toxicity and their tendency to oxidize.
Magnetic Nanoparticles (Mnps) In The Treatment Of Periodontal Diseases And Plaque Control

Targeted Drug Delivery with MNPs:

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• Recent research has shown that MNPs can improve drug delivery through the oral mucosa, enhance the mechanical and
microbiological properties
•Magnetic Induction for Targeted Attachment:
• A novel approach for treating periodontitis involves using magnetic induction to target antimicrobial MNPs (AMPs).

• These AMPs can anchor polyhexamethylene biguanide (PHMB), a potent antimicrobial agent, to directly treat periodontal
pockets where traditional agents struggle to penetrate

In Vitro Evidence of AMPs’ Therapeutic Impact

• In vitro antibacterial studies have shown that AMPs, when combined with magnetic induction, can clear bacterial biofilms,
including those of P. gingivalis, with an 80% clearance rate.

In Vivo Evidence of AMPs’ Therapeutic Impact

• In vivo studies on periodontitis models demonstrated significant therapeutic outcomes following treatment with AMPs.
Gingival redness and suppuration, common symptoms of periodontitis, disappeared after AMPs treatment.

• Quantitative micro-CT analysis revealed that groups treated with AMPs showed signs of alveolar bone development in contrast to
untreated periodontitis groups. Hematoxylin and eosin (HE) staining supported these findings, showing increased alveolar ridge
height, improved bone density, and reduced infiltration of inflammatory factors in AMP-treated groups.
NICKEL NANOPARTICLES
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Nano-nickel, like other nanomaterials, has an enhanced surface area, allowing greater contact with microbes and increased
antibacterial activity.
Use in Dental Compounds Nickel is frequently used in dental materials, particularly in improving the success rate of root fillings.
Antimicrobial Properties of NiNPs have shown antimicrobial properties against bacteria like S. aureus and E. coli.

Novel Coordination Complex:

Researchers created a new Ni(II)-containing coordination complex through a solvothermal process.
The substance significantly inhibited the growth of Porphyromonas gingivalis biofilm
 BISMUTH NANOPARTICLE
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• BiNPs have been investigated for their Bactericidal, Fungicidal, Antiparasitic, And Antibiofilm Properties.

• Non-Metallic BiNPs in BiomedicineResearch such as:Bismuth oxide (Bi₂O₃)Bismuth sulfide Bismuth selenide Bismuth telluride

These non-metallic forms have shown potential in biomedical applications

• possess unique features, including Affordability and scalability ,High stability ,chemical inertness ,Nontoxicity and compatibility with
biological systems and active characterstics

• BiNPs for Oral Infection Treatment could be a new strategy for treating dental caries and other oral infections (e.g., endocarditis,
septicemia) due to Low side effects compared to traditional drugs and low-cost, making them an affordable treatment option.

• BiNPs as a Potential Mouthwash Recent study suggest BiNPs could be used as an effective mouthwash to treat oral infections.

• They could potentially replace existing drugs due to their low toxicity and high effectiveness.

• Prevention of Biofilm Formation are effective in preventing the formation of S. mutans biofilms, which are responsible for most cases
of tooth decay.

• . Mechanism of Antimicrobial Action Electrostatic interaction between the positively charged BiNPs and the negatively charged
bacterial cell membrane plays a crucial role in their antimicrobial activity. Other mechanisms include: DNA damage Alteration of gene
expression on membrane-bound respiratory enzymes
Antibacterial Effect of Zerovalent Bismuth Nanoparticles (BiNPs)
• Zerovalent BiNPs were equally effective as Chlorhexidine (CHX), a standard oral antiseptic, in halting the spread of S. mutans, a key
bacterium responsible for tooth decay
• Minimum Inhibitory Concentration (MIC) of zerovalent BiNPs for bacterial growth inhibition was found to be 0.5 mM, suggesting their
potential as an effective oral antiseptic component.
• Biofilm Inhibition by Zerovalent BiNPsZerovalent completely stopped S. mutans from producing.
Experimental evidence suggests that BSS-Nano and zerovalent BiNPs have great potential as treatments for bacterial infections related to
biofilm formation in the oral cavity.

Laser-Ablated Bismuth Subsalicylate Nanoparticles (BSS-NPs):

Objective:
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• Evaluate the antibacterial efficacy of LASL-created BSS-NPs on subgingival biofilm samples from patients with periodontal
disorders.
• Antibacterial Efficacy:
• BSS-NPs suppressed over 30% of cultivable bacteria in oral biofilm samples.
• Potential alternative antibacterial treatment for periodontal disorders, reducing the reliance on antibiotics and combating
antibiotic resistance.
Zerovalent Bismuth Nanoparticles (BiNPs) Against Enterococcus faecalis: 20
• Investigated the effects of BiNPs on Enterococcus faecalis, a major cause of chronic root canal infections.
• Effective in preventing biofilm formation by S. mutans.Superior to CHX, suggesting potential for broader use in dental
treatments, particularly against E. faecalis.

Potential Risks:
• Acute renal impairment and Bi encephalopathy have been linked to high doses of Bi compounds.
 COBALT NANOPARTICLES
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Cobalt (Co): One of the most affordable transition metals.
•Effectiveness Against Bacteria:
• CoNPs demonstrated activity against S. aureus and E. coli in concentrations ranging from 0.125 to 128.0 g/ml.
• E. coli was more successfully inhibited by CoNPs compared to S. aureus.
•Superior Performance:
• CoNPs out performed bulk Co, oxytetracycline, and gentamicin.
• Greater activity index and fold rise observed with CoNPs, particularly at lower concentrations.
• showed superior antibacterial activity against S. aureus and E. coli compared to conventional antibacterials, especially at lower
doses.
•Biogenic Synthesis:
• Plant extracts
• Microbes
• Alge
• Bio molecule like starch and gelatin
A novel low-dimensional Co(II) coordination complex was synthesized through a solvothermal reaction using an unsymmetrical
tetracarboxylic acid and the 4,4′-bipyridine (bipy) ligand. 22
The complex was evaluated for its therapeutic efficacy against chronic periodontitis and its mechanism of action.

Key findings: Real-time RT-PCR results demonstrated that the compound can dose-dependently inhibit the survival genes in P.
gingivalis, the bacteria linked to chronic periodontitis.

This inhibition indicates that the complex could be a promising therapeutic agent for treating chronic periodontitis by targeting
bacterial gene expression.

•Cobalt and Cobalt Oxide NPs: Exhibit a wide range of medicinal capabilities, including:
• Antioxidant
• Antibacterial
• Antifungal
• Anticancer
• Larvicidal
• Antileishmanial
• Anticholinergic
• Wound-healing
• Antidiabetic
 COPPER NANOPARTICLES
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• Highly effective as multifunctional antibacterial agent
• Very inexpensive and environmentally safe
• Easily mix and bond with other metals, ceramics, and polymers.
• Products demonstrate physiochemical stability.

Applications in Dentistry:Dental amalgam, Restorative cements, Adhesives and resins, Endodontic-irrigation solution
, Dental implants, Orthodontic archwires and brackets
Antibacterial Mechanism:
Bacterial Interaction:
• Cu ions interact with the negatively charged carboxyl group of bacterial lipoproteins.
• Disrupt bacterial cell membranes, altering permeability.
• Cu ions penetrate cells, affecting cellular structures and proteins
Cellular Impact:
• Hamper biochemical functions leading to cell death.
• Interfere with enzyme activity, DNA, and protein synthesis.
• Stimulate hydrogen peroxide production.
• Damage bacterial cell membranes, causing leakage of essential cellular components
Chitosan-Copper Nanoparticles (CuNPs): A Novel Antibiotic Release System for Periodontal Treatment
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•Goal: Develop an antibiotic release system using chitosan and CuNPs to treat periodontal disease.
•Target Bacteria: Aimed at combating Aggregatibacter actinomycetemcomitans.

Materials Used: Chitosan - Biocompatible polymer

.Starch & Ascorbic Acid - Used in synthesis.CuNPs - Incorporated at a concentration of 100 μg/mL.
• Solid Sponges and Gel Spheres were created using CuNPs/chitosan gel nanocomposites.

Antibacterial Efficacy: Both sponges and gel spheres effectively inhibited the growth of A. actinomycetemcomitans.
•Sphere nanocomposites remained stable in saliva., Demonstrated prolonged release of Cu at bactericidal concentrations.
•Periodontal Therapy:
•Nanocomposites of CuNPs and chitosan show promise as a platform for developing targeted treatments for periodontitis.
•Offers a biocompatible and efficient alternative to traditional antibiotics, potentially reducing the risk of antibiotic resistance.
CONCLUSION
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Metal Nanoparticles as Promising Antibacterial Agents:
- Effective in combating drug-resistant bacterial strains.
- Superior to traditional treatments due to their high biocompatibility and long shelf life.
Mechanism of Action:
- Small size allows for penetration of biofilms and direct bacterial interaction.
- Inhibits biofilm formation, making them effective against persistent infections.
Future Potential:
- Continued research and advancements in synthesis and biomedical applications.
- Likely to see widespread use in medicine and health care, particularly in treating periodontal diseases.
Necessity for Further Research:
- Additional studies needed to fully understand the long-term effects and optimize usage in clinical settings.
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THANK YOU

MIRJAM NILSSON
[email protected] CONTOSO.COM
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REFERENCE 29
1. Recent advances in metal nanoparticles to treat periodontitis
Kamyar Nasiri , Seyed Mohammadreza Masoumi , Sara Amini, Mina Goudarzi , Seyed
Mobin Tafreshi ,
Abbas Bagheri , Saman Yasamineh6 , Mariem alwan7 , Meryelem Tania Churampi Arellano
and
Omid Gholizadeh

2. Vahedi M, Hosseini-Jazani N, Yousefi S, Ghahremani M. Evaluation of anti-bacterial effects of nickel

nanoparticles on biofilm production by Staphylococcus epidermidis. Iran J Microbiol. 2017
Jun;9(3):160-168. PMID: 29225755; PMCID: PMC571951

3. Wong PY, Soo S, Wong ES, Praveen P, Clode P, Baker MV, Matsubara VH. A Novel
Antimicrobial Hydrogel for the Management of Periodontal Diseases. Int Dent J. 2023
Jun;73(3):354-361. doi: 10.1016/j.identj.2023.01.002. Epub 2023 Feb 6. PMID: 36754776;
PMCID: PMC10213806.