Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension
, Motoyasu Miyazaki 4 and Arman Saparov 5Round 1
Reviewer 1 Report
Review of Medicina MS 792428
Micrograft Tissue Suspension Accelerates Epidermal Healing by Inducing Tissue Reactions on Cutaneous Wound in Mice
Comments to authors
This is a short study, but unfortunately there are many instances of incorrect grammer, poor English, typographical errors and poor formatting of the text which require correction. The figures also need attention. Comments are listed below outlining some of these. If you choose a re-write I would recommend you enlist the services of an English speaking colleague to ensure correctness of form.
abstract
Line 21 typo improvement improvement the donor area
Line 22 cover the substitutes after engraftment reword
Line 22 ineluctable side outcome this term is not English re-word
Line 23 inaesthetic scars. re-word
Line 35 the granulation were re-word
Line 36 suggest reword the term “was more than 3-times greater in the MG group than in the control group”.
Line 45 “granulation formation” suggest you add the word tissue between these two words
Line 52/53 “same authors” re-phrase this
Line 53 “cot” replace with correct English
Line 56-58 “Globally, the annual medical cost for patients with chronic wounds will increase up to 3.5 billion dollars in 2021 [9]. Moreover, there is still limited accessibility to easy, reliable, and reasonable technology for poorly treated cases in the world.” –this segment needs re-phrasing
Line 61 “Granulation” suggest you use the term granulation tissue
Line 69 surely there is a better term that could be used than “hashed” macerated, minced ?
Line 74 “dehiscence” what term is this –correct it
Line 76 “Complex trauma of the limbs, producing loss of skin and soft tissue, due to domestic or working injuries.”-suggest rewording more clearly
Line 78 “introduces a fullness new concept in regenerative surgery, enduring to repair severe traumatic wounds”- re-word this segment
Line 87 the figure legend needs more information-the legend as it stands is totally inadequate
Line 99 “Our splint model was used [30].”-sentence needs expansion
Line 101 “The part of the skin was excised with scissors.” Needs incorporation with surrounding sentences.
Line 108 suspension solution should be suspension solution
Line 112 what is Rigeneracons ?
Line 113/114 “was designated as tissue solution. A part of tissue solution (100 μL) in a 96-well multi plate was used” –does not make sense-reword. There is no such thing as a tissue solution-solubilised tissue extract-tissue suspension ?
Line 117/118 “for optimal concentration of tissue solution [21], tissue conce
Line 119 “surficial cells -did you mean superficial “
Line 120/121 “mimicking a deterred clinical wound”-re-word this and also following sentence
Line 124 explain the term WA%
Line 138 “its” be clearer
Line 141-149 define all abbreviations at first point of use
Line 157 “total spot numbers” did you mean pixels on the digitized image?
Line 167 “phosphate-buffered solution” did you mean phosphate buffered saline (PBS) ?
Line 170 “specimens were incubated in a tissue transparent reagent” is this a clearing agent or mountant ?
Line 182-183 “[contractive epithelial length (CEL), regenerative epithelial length (REL), and total epithelialization length (TEL)]” definitions of abbreviated terms should be used at their first point of use in the textstream.
Line 190 “Wound area (WA%)” this explanation of an abbreviated term should have been used earlier when it was first used in the text.
Line 202 The histological stain is too faint in Fig 2. The scale bars do not need to be given at an 100.0 accuracy, 100 um would have been fine.
Line 214 granulation tissue is the term that should be used. should “spots” more correctly be “histology pixel staining intensity” ?
Line 217 “halfway collapsed”-surely a better descriptive term could be used
Line 219 “Epidermal healing was evaluated as REL, CEL, and TEL.” is a rather awkward way to describe tissue changes surely a better more informative sentence could be constructed
Line 244 Fig 5A is extremely faint and very low magnification. Fig 5B is not in focus. Fig 5A needs to be described better in the legend. Can the skin surface be indicated with a fine dotted line? These images in segment A would be considerably improved at a higher magnification.
Line 252 “Wound healing could be achieved following comprehensive reactions”-please explain better
Line 252 “Therefore, enhancing one factor alone might be insufficient”. Is not a complete meaningful sentence.
Line 267 “minced tissue solution”-inaccurate term needs replacement
Line 268 contains cellular elements and other components” ?
Paragraph Lines 269-277. English construction needs improvement.
Paragraph Lines 278-287 English needs improvement
Paragraph Lines 298-310 English needs improvement
Line 314-315 “by which any kinds of clinically intractable wounds may be adaptable.”- unclear what the authors are attempting to convey-re-word more clearly
Line 319-322 “However, despite our conclusion, these results are still limited to explain complex tissue reactions after providing MG tissue suspension to wound tissues. Therefore, we have to profoundly consider the cellular interaction between the grafted tissue and wounded tissue in our future studies.” It isunclear what this section is trying to say, this section needs to be re-written to improve its clarity.
References The reference numbers are quite modest
Author Response
Thank you for your suggestions. Most of your suggestions have been incorporated, which are highlighted in red in the revised manuscript.
1 English and grammatical revision: We have corrected all the words and sentences according to your advice. Please refer to the revised manuscript.
2 Figures: especially Figs 2, 4 and 5 have been highlighted and enlarged as much as possible. The pictures on the manuscript prepared on Word look not enough resolution as they are. Thank you.
3 References: Micrograft-related references are still quite limited. We believe that all necessary references regarding micrograft are cited. At this time, we have added additional references.
4 The morphometrical method for neovascularization that we used was the point counting method; we checked the number of CD31-positive points on the lines that show depth of the granulation tissue. By using this approach, we can estimate neovascularization depending on the depth of the granulation tissue. Therefore, this is not a pixel-based method.
Reviewer 2 Report
micrograft tissue suspension accelerates epidermal healing by inducing tissue reactions on cutaneous w
The Authors performed an experimental study highlighting how micrograft tissue suspension accelerates epidermal healing by inducing tissue reactions on cutaneous wound in mice. The results are new, the topic interesting to a global audience.
Author Response
Thank you for useful reviewing our manuscript.
Reviewer 3 Report
Dear authors, I have completed reading your manuscript about micro graft tissue suspension. I find the idea interesting and definitely worth exploring further. My concern which you have not touched so much in your manuscript is the relevance to human wound healing and skin. As we know the human and rodent skin quite different. Not mention the underlying molecular responses. It would therefore be good if you could mention this in your introduction and your discussion as well.
It might be worth while checking for proliferation and IL-1 activation. That would give you a better view of what's happening in the activated area.
Your English gramma and composition needs to be improved in the all parts of the manuscript. Also please label and explain the images better. That way everyone will be able to follow you better in your results and conclusions.
Attached are some more direct comments to your manuscript.
Comments for author File: 
Comments.pdf
Author Response
Thank you for your suggestions. We have revised Figure 4 and grammatical errors, as well as added additional sentences according to your comments.
Please refer to the revised manuscript.
Round 2
Reviewer 1 Report
Review of Medicina MS 792428
Micrograft Tissue Suspension Accelerates Epidermal Healing by Inducing Tissue Reactions on Cutaneous Wound in Mice
Comments to authorsThis is a short study, but unfortunately there are many instances of incorrect grammer, poor English, typographical errors and poor formatting of the text which require correction. The figures also need attention. Comments are listed below outlining some of these. If you choose a re-write I would recommend you enlist the services of an English speaking colleague to ensure correctness of form.
abstract
Line 21 typo improvement improvement the donor area
Line 22 cover the substitutes after engraftment reword
Line 22 ineluctable side outcome this term is not English re-word
Line 23 inaesthetic scars. re-word
Line 35 the granulation were re-word
Line 36 suggest reword the term “was more than 3-times greater in the MG group than in the control group”.
Line 45 “granulation formation” suggest you add the word tissue between these two words
Line 52/53 “same authors” re-phrase this
Line 53 “cot” replace with correct English
Line 56-58 “Globally, the annual medical cost for patients with chronic wounds will increase up to 3.5 billion dollars in 2021 [9]. Moreover, there is still limited accessibility to easy, reliable, and reasonable technology for poorly treated cases in the world.” –this segment needs re-phrasing
Line 61 “Granulation” suggest you use the term granulation tissue
Line 69 surely there is a better term that could be used than “hashed” macerated, minced ?
Line 74 “dehiscence” what term is this –correct it
Line 76 “Complex trauma of the limbs, producing loss of skin and soft tissue, due to domestic or working injuries.”- suggest rewording more clearly
Line 78 “introduces a fullness new concept in regenerative surgery, enduring to repair severe traumatic wounds”- re-word this segment
Line 87 the figure legend needs more information-the legend as it stands is totally inadequate
Line 99 “Our splint model was used [30].”-sentence needs expansion
Line 101 “The part of the skin was excised with scissors.” Needs incorporation with surrounding sentences.
Line 108 suspensionsolution should be suspension solution Line
112 what is Rigeneracons ?
Line 113/114 “was designated as tissue solution. A part of tissue solution (100 μL) in a 96-well multi plate was used” –does not make sense-reword.
Line 117/118 “for optimal concentration of tissue solution [21], tissue conce
Line 119 “surficial cells -did you mean superficial “
Line 120/121 “mimicking a deterred clinical wound”-re-word this and also following sentence
Line 124 explain the term WA%
Line 138 “its” be clearer
Line 141-149 define all abbreviations at first point of use
Line 157 “total spot numbers” did you mean pixels on the digitized image?
Line 167 “phosphate-buffered solution” did you mean phosphate buffered saline (PBS) ?
Line 170 “specimens were incubated in a tissue transparent reagent” is this a clearing agent or mountant ?
Line 182-183 “[contractive epithelial length (CEL), regenerative epithelial length (REL), and total epithelialization length (TEL)]” definitions of abbreviated terms should be used at their first point of use in the textstream.
Line 190 “Wound area (WA%)” this explanation of an abbreviated term should have been used earlier when it was first used in the text.
Line 202 The histological stain is too faint in Fig 2. The scale bars do not need to be given at an 100.0 accuracy, 100 um would have been fine.
Line 214 granulation tissue is the term that should be used. should “spots” more correctly be “histology pixel staining intensity” ?
Line 217 “halfway collapsed”-surely a better descriptive term could be used
Line 219 “Epidermal healing was evaluated as REL, CEL, and TEL.” is a rather awkward way to describe tissue changes surely a better more informative sentence could be constructed
Line 244 Fig 5A is extremely faint and very low magnification. Fig 5B is not in focus. Fig 5A needs to be described better in the legend. Can the skin surface be indicated with a fine dotted line? These images in segment A would be considerably improved at a higher magnification.
Line 252 “Wound healing could be achieved following comprehensive reactions”-please explain better
Line 252 “Therefore, enhancing one factor alone might be insufficient”. Is not a complete meaningful sentence.
Line 267 “minced tissue solution”-inaccurate term needs replacement
Line 268 contains cellular elements and other components” ?
Paragraph Lines 269-277. English construction needs improvement.
Paragraph Lines 278-287 English needs improvement
Paragraph Lines 298-310 English needs improvement
Line 314-315 “by which any kinds of clinically intractable wounds may be adaptable.”- unclear what the authors are attempting to convey-re-word more clearly
Line 319-322 “However, despite our conclusion, these results are still limited to explain complex tissue reactions after providing MG tissue suspension to wound tissues. Therefore, we have to profoundly consider the cellular interaction between the grafted tissue and wounded tissue in our future studies.” It is unclear what this section is trying to say, this section needs to be re-written to improve its clarity.
References The reference numbers are quite modest and some seem quite obscure.
Author Response
We would like to thank the Reviewer for the heipful feedback.
Our comments are attched, please refer the word file.
Than you.
Author Response File: 
Author Response.docx
Reviewer 3 Report
Dear authors, Thanks for the correction and additions to your new version. I have only one minor correction. In row 347, you have spelled "akin" instead of "skin". I wish you good luck with your future research.
Author Response
We would like to thank the Reviewer for the helpul feedback.
We have corrected the word you had shown.
