Research Status of Silver Nanoparticles for Dental Applications

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The topic is relevant to the field of dentistry as it discusses the beneficial effects of AgNPs in killing dental bacteria for various dental treatments/applications such as dental implants, orthodontics, etc. However, AgNPs also induce cytotoxicity to several human cells in most cases. The safety use of AgNPs is a major concern for dental applications. As known, AgNPs can penetrate into human blood and cells during such treatments. There are no literature data in the manuscript reporting the  concentrations of AgNPs that are effective  for  killing dental bacteria and do not cause cytotoxicity to human cells· The manuscript can be improved by adding more references relating to this issue in the revised version, and list a new table tabulating the minimum concentrations of AgNPs for the viability of dental cells and other human tissue cells, but also effective for killing dental bacteria. The concentrations of AgNPs for effective killing dental bacteria but maintaining  biocompatibility should include in the Conclusions to strengthen the scientific merits of this review manuscript.

Author Response

The topic is relevant to the field of dentistry as it discusses the beneficial effects of AgNPs in killing dental bacteria for various dental treatments/applications such as dental implants, orthodontics, etc. However, AgNPs also induce cytotoxicity to several human cells in most cases. The safety use of AgNPs is a major concern for dental applications. As known, AgNPs can penetrate into human blood and cells during such treatments. There are no literature data in the manuscript reporting the concentrations of AgNPs that are effective for killing dental bacteria and do not cause cytotoxicity to human cells· The manuscript can be improved by adding more references relating to this issue in the revised version, and list a new table tabulating the minimum concentrations of AgNPs for the viability of dental cells and other human tissue cells, but also effective for killing dental bacteria. The concentrations of AgNPs for effective killing dental bacteria but maintaining biocompatibility should include in the conclusions to strengthen the scientific merits of this review manuscript.

Thank you for your suggestion. As to the cytotoxic and genotoxic effects in humans of AgNPs, it is very difficult to objectively compare the different studies because they include a wide variety of factors such as size, shape, coating, or stabilizers in addition to the diverse biological test models and the biomarkers used to identify toxicity. For example, a study in 2024 indicated that Ti-6Al-4V surfaces modified with 8 nm and 30 nm AgNPs at concentrations of 100 ppm, 200 ppm, and 300 ppm did not produce any serious cytotoxicity toward human gingival fibroblasts (HGFs). Another study showed that Argovit (35 nm PVP−AgNPs) and nanoComposix (50 nm PVP−AgNPs), at concentrations from 0.012 to 12 μg/mL, produce no changes in the nuclear division index (NDI) or micronuclei (MNi) frequency compared with the values found on control cultures of human blood peripheral lymphocytes from a healthy donor. Therefore, it is very hard to have the minimum concentrations of AgNPs included in the conclusion.

Reviewer 2 Report

Comments and Suggestions for Authors

The review titled "Research Status of Silver Nanoparticles for Dental Applications" provides an interesting overview of experimental findings regarding the use of silver nanoparticles in the dental field. The organization of the review is noteworthy, as it separates studies based on the application of nanoparticles to different oral cavity pathologies. However, there are several significant issues that the authors should address before the manuscript can be considered for publication.

Major revisions:

1. The manuscript does not specify how the studies included in the review were selected. What is the time frame considered? What types of studies were included? These aspects should be clarified.

2. In many sections, the studies are presented without offering any meaningful connection between them.

3. The conclusions are not adequately supported by the studies presented in the review.

4. The review does not provide any truly novel insights compared to other existing literature on the topic.

5. The bibliography is not sufficiently up to date.Minor revisions:

6. The authors should carefully proofread the manuscript to eliminate the numerous typographical errors and ensure consistency in terminology. In some sections, acronyms are used, while in others, terms are written in full (e.g., "nanoparticles" vs. "NPs"). The text should be standardized.

7. The units of measurement should be checked for accuracy and consistency.

Thus, the manuscript requires significant improvements in its presentation. More recent literature should be incorporated, and the studies discussed should be analyzed in greater depth.

Author Response

Answers for Reviewer 2:

Comments 1: The manuscript does not specify how the studies included in the review were selected what is the time frame considered? What types of studies were included? These aspects should be clarified.

Thank you for your suggestion. We conducted the review through PubMed in July 2022 using keywords such as “silver nanoparticles or AgNPs” (title/abstract), and “dental or dentistry” (title/abstract) from 2001. We additionally searched the key references from the relevant studies including reviews. The search was updated in Apil 2025. The reviewer monitored the retrieved studies against the inclusion and exclusion criteria in the beginning based on title and abstract and then on full texts. Published full-text research article in the English language were considered. We excluded studies in other languages.

Comments 2: In many sections, the studies are presented without offering any meaningful connection between them.

Thank you for your suggestion. The sections maintain logical coherence through their thematic progression. Taking the "Endodontic Treatment" section as an example, the first paragraph establishes silver nanoparticles (AgNPs) as multifunctional agents in endodontics, highlighting their evaluation as endodontic irrigants, intracanal medicaments, and root filling materials, including modified gutta percha and incorporated mineral trioxide aggregate (MTA). This comprehensive introduction sets the framework for subsequent detailed discussions.

The second paragraph substantiates these claims by presenting evidence from representative studies demonstrating the effectiveness of AgNPs as endodontic irrigants. Building upon this foundation, the third paragraph logically extends the discussion to two additional applications: their use as intracanal medicaments and their incorporation into modified gutta-percha formulations. 

The fourth paragraph then explores the expanded clinical utility of MTA enhanced with AgNPs, detailing its various endodontic applications including direct pulp-capping, apexification, and repair of complex canal defects. 

Finally, the concluding paragraph synthesizes these findings to emphasize AgNPs' significant potential as valuable adjuncts in root canal therapy. 

Comments 3: The conclusions are not adequately supported by the studies presented in the review.

Thank you for your suggestion. This section presents the conclusions and outlines potential avenues for future research. Therefore, it has many uncertain issues and concerns.

Comments 4: The review does not provide any truly novel insights compared to other existing literature on the topic.

Thank you for your suggestion. We have incorporated numerous additional references and thoroughly revised the relevant discussion.

Comments 5: The bibliography is not sufficiently up to date.

Thank you for your suggestion. We conducted the review through PubMed in July 2022. The search has been updated in Apil 2025, and fifteen studies are added into the review (ref. 62, 77, 78, 79, 80, 90, 91, 92, 124, 125, 171, 172, 177, 189, 190).

Comments 6: The authors should carefully proofread the manuscript to eliminate the numerous typographical errors and ensure consistency in terminology. In some sections, acronyms are used, while in others, terms are written in full (e.g., "nanoparticles" vs. "NPs".

Thank you for your suggestion. We have carefully proofread the manuscript to eliminate the numerous typographical errors and ensure consistency in terminology. For example, in the first place, the terms are written in full, while in others, acronyms are used (e.g., "nanoparticles" vs. "NPs", "Streptococcus mutans" vs. "S. mutans", " Enterococcus faecalis" vs. "E. faecalis", "Staphylococcus aureus" vs. "S. aureus", "Candida albicans" vs. "C. albicans", "Aggregatibacter actinomycetemcomitans" vs. "A. actinomycetem", "Escherichia coli" vs. "E. coli", "Lactobacillus casei" vs. "L. casei").

Comments 7: The units of measurement should be checked for accuracy and consistency.

Thank you for your suggestion. We have carefully checked the accuracy of the measurement. However, as to the consistency of the units of measurement, it is very difficult to standardize because the different research studies used their own test models (e.g. ppm, percentage, or ug/mL).

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for giving me the opportunity of reviewing  your manuscript entitled 'Research status of silver nanoparticles for dental applications`. The review paper focused on the  effects of nanoparticles on antimicrobial properties and presented the current knowledge about the antimicrobial use of silver nanoparticles in detistry,highlighting their antimicrobial mechanism, and potential applications in clinical treatment. This paper contains a lot of important informations which can contribute the development of the new methods using silver nanoparticles in  antimicrobial treatments in all aspects of dental treatment. But there is one thing to improve the paper.  Page 7-8  3.3. in 'Endodontic Treatment` paragraph, authors described the combination of diode laser and nanoparticles. Authors should describe more detailed mechanisms between diode laser and nonopariticles in antimicrobial  properties. I strongly think that it's better to delete this sentence.

Best regards

Author Response

Answers for Reviewer 3:

Comments 8: But there is one thing to improve the paper. Page 7-8 3.3. in 'Endodontic Treatment` paragraph, authors described the combination of diode laser and nanoparticles. Authors should describe more detailed mechanisms between diode laser and nanoparticles in antimicrobial properties. I strongly think that it's better to delete this sentence.

Thank you for your suggestion. We have deleted this paragraph. "In 2021, Hendi investigated antibacterial efficacy of 940 nm diode laser with or without AgNPs against E.faecalis. Ninety single-rooted teeth were included and randomly separated into five groups: hypochlorite sodium 5% (n = 10), silver nanoparticles (n = 20), diode laser (n = 20), diode laser and silver nanoparticles (n = 20). Hypochlorite sodium 5% has the highest bacterial elimination (RCC = 100), while silver nanoparticles were the second effective antibacterial substances (P value < 0.001). "

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed the necessary revisions in a satisfactory manner. The manuscript has been improved accordingly and is now suitable for publication in its current form.