Use of Metallic Nanoparticles Synthesized from Plant Extracts in Wound Healing—A Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript can be accepted after a major revision.

1.    The manuscript focused on exploring how metallic nanoparticles can be used to promote wound healing, but the overall coherence and sequential logic seems unclear. It is suggested adding a subsection in Section 3 to analyze in detail the functional mechanisms of different metallic nanoparticles for wound healing. This subsection should deepen understanding and reinforce concepts with specific and pertinent examples.

2.    Some redundancy is observed between the summary of nanotechnology in Section 3.4 and the overview of nanoparticle synthesis in Section 3.5. It is recommended that Sections 3.4 and 3.5 be merged and rephrased to avoid duplication.

3.    The understanding and summarization of nanoparticle synthesis (Section 3.5) appears rudimentary, not reaching the depth expected of a paper review. A comprehensive recapitulation is required, incorporating aspects like the synthesis mechanisms of different metallic nanoparticles, synthesis conditions, methodologies employed, and experimental characterization results such as size and shape, instead of showing summary tables only. Furthermore, including SEM images or other related characteristic results is also recommended to display the nanoparticles of different categories, sizes, or shapes.

4.    As described in the abstract, if the focus of this manuscript is on the application of Ag, Au, Zn, then both Tables 1 and 2 need revision. For instance, the content concerning Ti and Ce should be removed from Table 1, while Au and Zn should be added to Table 2. Conversely, if the author intended to give a comprehensive overview of the applications of different metallic nanoparticles, not restricted to Ag, Au, and Zn, more examples need to be included in Table 1; similar changes should reflect in Table 2.

Minor revision:

1.    In Section 3.6, the authors described Figure 2, but it was not included in the text. Please add.

Author Response

Manuscript: applnano-2814799

Title: Use of metallic nanoparticles synthesized from plant extracts in the wound healing – A review

Dearest reviewer #1, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted in red in the revised version of the manuscript.

This manuscript can be accepted after a major revision.

R.: Thank you for pointing this out.

1. The manuscript focused on exploring how metallic nanoparticles can be used to promote wound healing, but the overall coherence and sequential logic seems unclear. It is suggested adding a subsection in Section 3 to analyze in detail the functional mechanisms of different metallic nanoparticles for wound healing. This subsection should deepen understanding and reinforce concepts with specific and pertinent examples.

R.: Thank you for your recommendation. We have reorganized Section 3 to achieve the requirement of the reviewer.

2. Some redundancy is observed between the summary of nanotechnology in Section 3.4 and the overview of nanoparticle synthesis in Section 3.5. It is recommended that Sections 3.4 and 3.5 be merged and rephrased to avoid duplication.

R.: Thank you for your recommendation. Please see the new topic 3.4. Nanotechnology and nanoparticles at line 223.

3. The understanding and summarization of nanoparticle synthesis (Section 3.5) appears rudimentary, not reaching the depth expected of a paper review. A comprehensive recapitulation is required, incorporating aspects like the synthesis mechanisms of different metallic nanoparticles, synthesis conditions, methodologies employed, and experimental characterization results such as size and shape, instead of showing summary tables only. Furthermore, including SEM images or other related characteristic results is also recommended to display the nanoparticles of different categories, sizes, or shapes.

R.: Thank you for your recommendation. We have reorganized Section 3 to achieve the requirement of the reviewer. New information was added considering the synthesis mechanisms of different metallic nanoparticles, synthesis conditions, methodologies employed, and experimental characterization. Figures 2, 3, and 4 were added to complement the theoretical content.

4. As described in the abstract, if the focus of this manuscript is on the application of Ag, Au, Zn, then both Tables 1 and 2 need revision. For instance, the content concerning Ti and Ce should be removed from Table 1, while Au and Zn should be added to Table 2. Conversely, if the author intended to give a comprehensive overview of the applications of different metallic nanoparticles, not restricted to Ag, Au, and Zn, more examples need to be included in Table 1; similar changes should reflect in Table 2.

R.: Thank you for your recommendation. We have modified Tables 1 and 2 in a singular Table 1 trying to reach the reviewers´ requirement.

Minor revision:

1. In Section 3.6, the authors described Figure 2, but it was not included in the text. Please add.

R.: Thank you for your alert. Please see the Figure 2 added in the revised version of the manuscript at lines 376-377.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

1.       The process of wound healing is described in detail in section 3.1. However, there is no mention of how nanoparticles promote wound healing, please add the mechanism for this.

2.      In section 3.6, the author only mentions the silver nanoparticles part of section 3.6.1, and lacks the analysis of other kinds of nanoparticles such as gold, zinc, titanium and so on. Please add the relevant content.

3.      Section 3 contains too many things, it is suggested to divide it into two sections, which are natural plant extracts and nanoparticles, for readers to read more clearly.

Comments on the Quality of English Language

Need to find native English speakers or professional institutions to polish.

Author Response

Manuscript: applnano-2814799

Title: Use of metallic nanoparticles synthesized from plant extracts in the wound healing – A review

Dearest reviewer #2, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted in red in the revised version of the manuscript.

1.      The process of wound healing is described in detail in section 3.1. However, there is no mention of how nanoparticles promote wound healing, please add the mechanism for this.

R.: Thank you for your recommendation. We have reorganized Section 3 to achieve the requirement of the reviewer. Please see subtopics 3.6.1, 3.6.2, and 3.6.3 of the revised manuscript.

2. In section 3.6, the author only mentions the silver nanoparticles part of section 3.6.1, and lacks the analysis of other kinds of nanoparticles such as gold, zinc, titanium and so on. Please add the relevant content.

R.: Thank you for your recommendation. Please see subtopics 3.6.1, 3.6.2, and 3.6.3 of the revised manuscript.

3. Section 3 contains too many things, it is suggested to divide it into two sections, which are natural plant extracts and nanoparticles, for readers to read more clearly.

R.: Thank you for your recommendation. We have reorganized Section 3 to achieve the requirement of the reviewer. Please see the revised version of the manuscript.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The document “Use of metallic nanoparticles synthesized from plant extracts in the wound healing – A review” focused on the study of nanoparticles green synthesis that can be applied in health care. In vitro and in vivo tests were used to assess the efficiency of plant extracts. Authors used the scielo, Pubmed and sciencedirect data base to obtain the scientific articles that were further analyzed in pairs. The word keys used to find the articles were wound healing, nanotechnology, metallic nanoparticles, green synthesis and others. After the review, it can be observed some issues that need to be addressed.

Comments:

1) The abstract describes the document but it can be improved.

2) Add relevant information to the abstract section such as the best plant extract (in terms of yield) and the best material in terms of therapeutic application.

3) The introduction section mentions “For this reason, several strategies have been the subject of recent studies to improve wound healing”. What are those strategies reported in the literature? Moreover, it should be important to add other references to clarify the importance and the difference of this manuscript in comparison with those previously published. 

And clarify what is the novelty of this work in comparison with the last document 

Nanoparticle-based therapeutic approaches for wound healing: a review of the state-of-the-art - ScienceDirect

Nanomaterial-Based Therapy for Wound Healing - PMC (nih.gov)

Wound healing strategies based on nanoparticles incorporated in hydrogel wound patches - PMC (nih.gov)

4) The methodology does not mention the year publication please use articles from 2020-2024.

5) Include case studies and web reports.

6) Add future work and perspective

7) Figure 1 needs to be improved, has low quality.

8) In the result section author adds the section 3.1 but does not relate the importance of nanoparticles during the wound healing process. How are the mechanisms of nanoparticles or what of the pathway is favoured?

9) Table 2 requires more information. What about particle size, morphology, superficial area, yield, cost, is metal Ag or oxidized Ag, etc.

10) Is necessary to add more relevant references in 3.5.2 and 3.5.2.1 and 3.6 sections.

Author Response

Manuscript: applnano-2814799

Title: Use of metallic nanoparticles synthesized from plant extracts in the wound healing – A review

Dearest reviewer #3, thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted in red in the revised version of the manuscript.

The document “Use of metallic nanoparticles synthesized from plant extracts in the wound healing – A review” focused on the study of nanoparticles green synthesis that can be applied in health care. In vitro and in vivo tests were used to assess the efficiency of plant extracts. Authors used the scielo, Pubmed and sciencedirect data base to obtain the scientific articles that were further analyzed in pairs. The word keys used to find the articles were wound healing, nanotechnology, metallic nanoparticles, green synthesis and others. After the review, it can be observed some issues that need to be addressed.

R.: Thank you for pointing this out.

Comments:

1) The abstract describes the document but it can be improved.

R.: Thank you for your recommendation. We have modified the abstract to achieve the reviewer requirement.

2) Add relevant information to the abstract section such as the best plant extract (in terms of yield) and the best material in terms of therapeutic application.

R.: Thank you for your recommendation. Please see the new information added to the revised abstract: “Finally, we address in vitro and in vivo studies on the efficiency of metallic nanoparticles (MNPs) synthesized from plant extracts and applied to wound healing in different pharmaceutical forms. For instance, the excellent wound contraction rates obtained from silver and gold NPs respectively from Euphorbia milii (92%) and Plectranthus aliciae (almost 97%) extracts in in vivo and in vitro analyses. Based on the satisfactory results, we find that MNPs are a potential therapeutic alternative when compared to traditional synthetic healing agents and foresee the production of new pharmaceutical drugs”.

3) The introduction section mentions “For this reason, several strategies have been the subject of recent studies to improve wound healing”. What are those strategies reported in the literature? Moreover, it should be important to add other references to clarify the importance and the difference of this manuscript in comparison with those previously published. 

And clarify what is the novelty of this work in comparison with the last document 

R.: Thank you for your recommendation. We consider the novelty of this work the revision of the most recent in vivo and in vitro studies on the use of MNPs synthesized from plant extracts as healing agents. We have modified the Introduction section trying to highlight the difference between this work and those already reported by the scientific literature.

Nanoparticle-based therapeutic approaches for wound healing: a review of the state-of-the-art - ScienceDirect

Nanomaterial-Based Therapy for Wound Healing - PMC (nih.gov)

Wound healing strategies based on nanoparticles incorporated in hydrogel wound patches - PMC (nih.gov)

R.: Thank you for your recommendation.

4) The methodology does not mention the year publication please use articles from 2020-2024.

R.: Thank you for your recommendation. Please see the added information to the Method section of the revised manuscript: “Research articles of the last 10 years presenting wound closure rates from in vivo and in vitro healing activity evaluations were preferred over those from previous periods.”

5) Include case studies and web reports.

R.: Thank you for your recommendation. Please see subtopics 3.6.1, 3.6.2, and 3.6.3 of the revised manuscript and the New Table 1 with more references.

6) Add future work and perspective

R.: Thank you for your recommendation. Please see the added information to the Conclusions of the revised manuscript: “We visualize future review works based on the perspective of large-scale production of drugs containing greenly synthesized NPs. Those formulations could depict NPs as promising compounds for the industry, thus allowing their production in an available form to the general population and, consequently, suggesting the prevention of complications from poor healing and/or infections, significantly improving the quality of life of patients by reducing aesthetic discomfort and the clinical and financial burden, among others.”

7) Figure 1 needs to be improved, has low quality.

R.: Thank you for your recommendation. The quality of the image was improved accordingly.

8) In the result section author adds the section 3.1 but does not relate the importance of nanoparticles during the wound healing process. How are the mechanisms of nanoparticles or what of the pathway is favoured?

R.: Thank you for your recommendation. We have modified the manuscript trying to reach the reviewer's requirement. Please see subtopics 3.6.1, 3.6.2, and 3.6.3 of the revised manuscript.

9) Table 2 requires more information. What about particle size, morphology, superficial area, yield, cost, is metal Ag or oxidized Ag, etc.

R.: Thank you for your recommendation. We have modified the manuscript trying to reach the reviewer's requirement. Please see new subtopics 3.4.1.1 Physical synthesis, 3.4.1.2 Chemical synthesis, 3.4.2.1 Green synthesis from plant extracts, and 3.5. Characterization of MNPs, in addition to Figure 4, with more information about the characteristics of NPs.

10) Is necessary to add more relevant references in 3.5.2 and 3.5.2.1 and 3.6 sections.

R.: Thank you for your recommendation. We have modified the manuscript trying to reach the reviewer's requirement. Please see new references in the subtopics 3.6.1, 3.6.2, and 3.6.3, in addition to the new Table 1 of the revised manuscript.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript can be accepted for publication.

Reviewer 3 Report

Comments and Suggestions for Authors

After reading the "Use of metallic nanoparticles synthesized from plant extracts in 2 the wound healing – A review" manuscript it can be seen a lot of improvement. Authors address the commends from the first round. So, the document has good quality to be considering publishing in the applied Nano Journal.