Nanometric-Scale-Polished, Engineered Surgical Scalpel Blades Reduce Tissue Inflammation and Scarring
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsMy suggestions for correction are:
1. The results show that the wound treated with SB does not close completely on the third day; however, the one treated with EB does.
2. There are no signs of infection in any of the wounds. Is this possible?
3. It would be exciting to show the wounds the following day (day 1) after the incision (day 0), allowing the healing process to be appreciated.
4. It would be interesting to investigate the expression of other inflammatory markers, such as interleukins, to obtain a more complete view of the inflammatory response induced by the different types of scalpel blades.
5. The proposed work's conclusion is correct and in line with the study's results. However, "on an almost atomic scale" could be slightly exaggerated since the nanoscale covers many sizes. It would be more accurate to describe "on a nanometric scale."
Author Response
Comment 1: The results show that the wound treated with SB does not close completely on the third day; however, the one treated with EB does.
Response 1: Thank you for pointing this out. We agree with this comment. Therefore, we have added this statement to page 5 under Wound Healing Observations, lines 197-198.
Comment 2: There are no signs of infection in any of the wounds. Is this possible?
Response 2: Yes, this is possible and is what was observed. To clarify, we have added the following statement, "Standard operating precautions to prevent infection were employed." to page 2 (first paragraph under Animals), lines 91-92.
Comment 3: It would be exciting to show the wounds the following day (day 1) after the incision (day 0), allowing the healing process to be appreciated.
Response 3: We agree that this could be exciting! Therefore, in our discussion section's last paragraph, the authors have added the following — "Also, while the wound was excised at five time points, studying additional intermediate and later time points may provide a more comprehensive understanding of wound healing progression".
Comment 4: It would be interesting to investigate the expression of other inflammatory markers, such as interleukins, to obtain a more complete view of the inflammatory response induced by the different types of scalpel blades.
Response 4: Thank you for this comment. We agree that other inflammatory markers could provide additional insight. We used a few well-established markers for this initial study, but future studies could definitely expand on our findings to provide a more comprehensive understanding. Therefore, in our discussion section's last paragraph we have added — "Last, additional inflammatory markers could be studied to provide a more comprehensive understanding of the healing process".
Comment 5: The proposed work's conclusion is correct and in line with the study's results. However, "on an almost atomic scale" could be slightly exaggerated since the nanoscale covers many sizes. It would be more accurate to describe "on a nanometric scale."
Response 5: Thank you for pointing this out. The authors agree and have changed every use of nanoscale to nanometric scale throughout the paper.
Reviewer 2 Report
Comments and Suggestions for AuthorsHello, dear colleagues!
Your research opens up new possibilities in surgery and regeneration, so its relevance is hard to overestimate. At the same time, there are a number of critical comments to the article that I would like to voice
1. The abstract does not have headings for "introduction", "goal", "materials and methods", etc.
2. How many animals participated in the experiment and how was the sample size calculated?
3. What was the concentration of epinephrine in the local anesthetic solution?
4. You write that histology was taken at 1, 3, 7, 16 and 60 days post-surgery: clarify the collection technology and depth, as well as the instrument used to collect tissue. It is also necessary to clarify how the animal's wound was cared for. I am afraid that such frequent tissue extraction could lead to cicatricial deformations.
5. The sections "Relevance" and "Discussion" are written in a very concise and uninformative manner, which is due to the insufficient number of sources in the list of references.
6. The list of references must be formatted according to the requirements of the journal, and must be expanded and supplemented with modern references.
Author Response
Comment 1: The abstract does not have headings for "introduction", "goal", "materials and methods", etc.
Response 1: Thank you for pointing this out. We have added the appropriate sections to the abstract (Background, Objectives, Methods, Results, Conclusions).
Comment 2: How many animals participated in the experiment and how was the sample size calculated?
Response 2: Thank you for your questions. In lines 17-18, we mention how many animals participated, specifically "The wound was excised at 5 time points (1, 3, 7, 16, and 60 days) with 5 animals per group." In addition, in lines 187-189, we mention, "Two animals were lost and removed from the study due to signs of immediate post-anesthesia distress. Both animals were replaced with animals that experienced the surgery successfully, without presenting any signs of pain or distress." Regarding how sample size was determined, please see the Materials & Methods Statistical Analysis paragraph (lines 177-178). We used a power calculation to determine the minimum size needed for the study. We used a lower threshold to minimize the use of animals.
Comment 3: What was the concentration of epinephrine in the local anesthetic solution?
Response 3: The authors have added this information, specifying the ratio of epinephrine in water (1:200,000) on page 3 (first full paragraph), specifically line 118.
Comment 4: You write that histology was taken at 1, 3, 7, 16 and 60 days post-surgery: clarify the collection technology and depth, as well as the instrument used to collect tissue. It is also necessary to clarify how the animal's wound was cared for. I am afraid that such frequent tissue extraction could lead to cicatricial deformations.
Response 4: Please see the Material & Methods Skin Incision and Repair Section where we address these comments.
Comment 5: The sections "Relevance" and "Discussion" are written in a very concise and uninformative manner, which is due to the insufficient number of sources in the list of references.
Response 5: Thank you for the feedback. The authors have restructured the introduction and discussion sections. We have expanded and included more references to both. We now have 19 references total. Regarding relevance, we now have three paragraphs in the discussion (starting with "Nevertheless" (line 311), "Moreover" (line 316), and "Alternately" (326)) that focus on clinical implications.
Comment 6: The list of references must be formatted according to the requirements of the journal, and must be expanded and supplemented with modern references.
Response 6: Thank you for this comment. The authors have formatted all references according to the journal requirements. The authors have also put all in-text citation numbers in brackets. The authors have now supplemented with modern references.
Reviewer 3 Report
Comments and Suggestions for AuthorsThis is an interesting study.
Could the authors provide more context on the current state of surgical steel blade quality, particularly at the cutting edge? Additionally, what specific quality improvements were the authors aiming to achieve in this study?
What was the study’s primary endpoint?
Could the clinical implications of the findings be elaborated on further?
The limitations section would benefit from a more detailed discussion.
Author Response
Comment 1: Could the authors provide more context on the current state of surgical steel blade quality, particularly at the cutting edge? Additionally, what specific quality improvements were the authors aiming to achieve in this study?
Response 1: Thank you for this suggestion. The authors have added context about the current state of surgical steel blades and a reference in the Introduction that addresses these comments (lines 37-47).
Comment 2: What was the study’s primary endpoint?
Response 2: We have added appropriate sections to the abstract (Background, Objectives, Methods, Results, Conclusions). Our study's objective was the following: "To test the hypothesis that use of precision sharpened scalpel blades would result in less tissue inflammation and incisional scarring".
Comment 3: Could the clinical implications of the findings be elaborated on further?
Response 3: Thank you for this feedback. Yes, of course. In the discussion, we now have three paragraphs that focus on clinical implications (starting with "Nevertheless", "Moreover", and "Alternately").
Comment 4: The limitations section would benefit from a more detailed discussion.
Response 4: Thank you for this suggestion. The last paragraph in the discussion section now focuses on limitations and future studies that could better our findings.
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsDear colleagues, hello!
In its current form, the work looks more presentable, however, the calculation of the dose of local anesthetic and the single volume injected into the animal are not obvious.
I also draw your attention to the need to describe the nanometric scale in more detail, chewing with a microphotograph
The list of references still causes some confusion: you write that the study is relevant, but the age of a number of references exceeds 5 and 10 years. I recommend conducting a review of this section
Author Response
Comment 1: In its current form, the work looks more presentable, however, the calculation of the dose of local anesthetic and the single volume injected into the animal are not obvious.
Response 1: Thank you for your comment. To clarify, the animals were asleep, under general anesthesia. The anesthetic was applied locally (just enough to spread over the area of incision) and was nowhere near a toxic dose. The dose remained well within safety margins. Anesthetic depth was rechecked and adjusted as needed by the veterinary staff to maintain the animal's welfare.
Comment 2: I also draw your attention to the need to describe the nano-metric scale in more detail, chewing with a microphotograph
Response 2: Thank you for this comment. We have added the following description and associated reference "CMP allows for the outer atomic layer of several ceramic and metal surfaces to be softened following a set of chemical reactions. The softened surface is extracted by mechanical forces exercised by a polishing tool, pad, and associated microscopic particles. The process reliably creates surfaces of near-atomic perfection while the blade’s core mechanical attributes remain unchanged [13]." This can be seen in the manuscript from lines 84-88.
In addition, we added "Optical microphotographs illustrate the difference [13,19]" (line 78) so that the reader can access microphotographs of the respective blades.
Comment 3: The list of references still causes some confusion: you write that the study is relevant, but the age of a number of references exceeds 5 and 10 years. I recommend conducting a review of this section
Response 3: Thank you for the suggestion. We have added updated references.
Round 3
Reviewer 2 Report
Comments and Suggestions for AuthorsHello!
Thank you for your comments: in this form I can approve your research for publication
Author Response
Comment: Hello! Thank you for your comments: in this form I can approve your research for publication.
Response: Thank you!
