Recent Advances in Biodegradable and Biocompatible Synthetic Polymers Used in Skin Wound Healing

Round 1

Reviewer 1 Report

Manuscript titled „Recent advances of biodegradable and biocompatible synthetic polymers used in skin wound healing” is a good source of information about polymers used in skin regeneration. It is well organized and prepared in a clear manner, however, there are several things that could be improved. Scan your manuscript for possible typos, like: line 438: not necessary F in citation, line 455: “tp” instead of “to” etc.

Detailed comments:

Line 60: How is better wear resistance of synthetic polymers relevant for wound healing applications? Are polymers susceptible to corrosion?

Line 74: Add also PU in named polymers you described. Abbreviations used for the first time in the text should be explained in full name.

Line 76: Be consistent in the manuscript about describing manufacturing methods for materials used in skin wound healing, hydrogel or foam and sponge are not fabrication methods, but forms of prepared materials. It should be corrected in paragraph 2, Figure 1 and other places in the manuscript, like first sentence of conclusions. Is there any significant difference between sponge and foam? If yes, you should explain it. How materials prepared by particles leaching are different from sponges? You should also include freeze-drying method, it is frequently applied for wound patches production.

Line 102: Electrospinning and electrospraying are two different processes, even if some theoretical aspects of both are the same, and they resulting in very distinct morphology of obtained materials. Be careful which term you use while writing.

Line 108: Correct term is “applied voltage”.

Line 163: “Receiver” in electrospinning is called “collector”, please correct in Figure 1.

Line 163: From the schematic it is not clear if the polymers are assigned to individual production methods, e.g. PLA is manufactured only by electrospinning?

Line 243: There is no need to repeat multiple times the full name and abbreviations of various materials, once given is enough. You can write in the figure caption only the abbreviations and in the last sentence explain all of them.  

Line 457: You can shorten the first sentence, just write “Examples of polymeric constructs for skin tissue engineering scaffolds”. Similarly like for Figure 3, there is no need to repeat the abbreviations, just once in the last sentence explain all of them used in the figure caption.

Line 474: Table 1 in not mentioned anywhere in your manuscript. Add relevant information in the text what can be found in the Table 1.

Line 475: Term “application method” is misleading, it suggest how the material should be applied on the wound. Either describe this column as “manufacturing method” (then you need to change sponge, foam etc. to relevant production technique) or ”form of scaffold (then you need to replace electrospinning with electrospun fibers etc.).

Conclusions: You wrote: “Due to the intricate dynamic … the selection of polymers and fabrication technique should be depended on specific requirements.” Do you have any indications of which material in what form would be desired in particular situation of burns or diabetic wound etc.? You wrote: “Nowadays, wound dressings are moving towards intelligent, personalized and high-end complex functions…. real-time monitoring…” can you add some examples from literature to support this statements?

The quality of English is good, the manuscript is clear, only some typos that I could point.

Author Response

1. Scan your manuscript for possible typos, like:

Line 438: not necessary F in citation.

Line 455: “tp” instead of “to” etc.

A: Thank you very much for your corrections. We apologize for the careless typos, which have been corrected at Line 445 and 462 accordingly.

2. Line 60: How is better wear resistance of synthetic polymers relevant for wound healing applications? Are polymers susceptible to corrosion?

A: Many thanks for your important and valuable comments. We agree with the reviewer’s opinion that although synthetic polymers can be modulated to possess better wear resistance and corrosion resistance by adjusting their molecular structure and chemical formulation, when comparing to natural polymers. However, the relevance of wear resistance and corrosion resistance for wound healing is relatively small. Therefore, we deleted the expressions "wear resistance" and "corrosion resistance" and revised our description at Line 59.

3. Line 74: Add also PU in named polymers you described. Abbreviations used for the first time in the text should be explained in full name.

A: Thanks very much for your valuable suggestions. We have added the full name- polyurethane before the abbreviation PU at Line 74 for the first time when PU was used.

4. Line 76: Be consistent in the manuscript about describing manufacturing methods for materials used in skin wound healing, hydrogel or foam and sponge are not fabrication methods, but forms of prepared materials. It should be corrected in paragraph 2, Figure 1 and other places in the manuscript, like first sentence of conclusions. Is there any significant difference between sponge and foam? If yes, you should explain it. How materials prepared by particles leaching are different from sponges? You should also include freeze-drying method, it is frequently applied for wound patches production.

A: Thanks a lot for your valuable comments and suggestions. We reformatted this chapter and classified it according to the fabrication methods. Accordingly, we renamed the subtitle "hydrogel" to "hydrogel formation" to make it suitable for a fabrication method. In addition, we added the hydrogel fabrication techniques including template method, 3D printing, solvent casting, hydrogel self-assembly, etc in this section. We agree with the reviewer that sponges and foams are not fabrication methods, but forms of prepared materials, and thus we deleted the section "Sponges/foams" in the revised manuscript. Furthermore, many thanks for the suggestion of including freeze-drying method, we have added this section in the text. Finally, we revised Figure 1 and checked throughout the manuscript and corrected the corresponding places including the first sentence of conclusions.

5. Line 102: Electrospinning and electrospraying are two different processes, even if some theoretical aspects of both are the same, and they resulting in very distinct morphology of obtained materials. Be careful which term you use while writing.

A: Many thanks for your valuable comments. We have realized that electrospinning and electrospraying are different processes, so we have revised the word “spraying” to “microjet” in the text at Line 111.

6. Line 108: Correct term is “applied voltage”.

A: Many thanks for your valuable comments. We have replaced the term “spinning voltage” by “applied voltage” as suggested at Line 119.

7. Line 163: “Receiver” in electrospinning is called “collector”, please correct in Figure 1.

A: Many thanks for your correction. We have corrected “Receiver” to “collector” in Figure 1.

8. Line 163: From the schematic it is not clear if the polymers are assigned to individual production methods, e.g. PLA is manufactured only by electrospinning?

A: We apologize for the misleading in the previous schematic. The polymers are not assigned to individual production methods. For clarity, we have revised Figure 1 and omitted the polymer part.

9. Line 243: There is no need to repeat multiple times the full name and abbreviations of various materials, once given is enough. You can write in the figure caption only the abbreviations and in the last sentence explain all of them.

A: Thanks very much for your valuable suggestions! We write in the figure caption only the abbreviations and in the last sentence explain all of them for Figure 3 as suggested.

10. Line 457: You can shorten the first sentence, just write “Examples of polymeric constructs for skin tissue engineering scaffolds”. Similarly like for Figure 3, there is no need to repeat the abbreviations, just once in the last sentence explain all of them used in the figure caption.

A: We highly agree with your comments and have shorten the first sentence to "Examples of polymer structures for skin tissue engineering scaffolds". Repeated abbreviations have been removed, with explaining all the abbreviations used in the figure caption in the last sentence.

11. Line 474: Table 1 is not mentioned anywhere in your manuscript. Add relevant information in the text what can be found in the Table 1.

A: Thanks very much for your important reminding! We have added some description to mention “Table 1” at Lines 189-191 on page 5.

12. Line 475: Term “application method” is misleading, it suggest how the material should be applied on the wound. Either describe this column as “manufacturing method” (then you need to change sponge, foam etc. to relevant production technique) or ”form of scaffold (then you need to replace electrospinning with electrospun fibers etc.).

A: Many thanks for your valuable suggestion! We replaced the term “Application method” with “Form of scaffold” to describe the column. We also replaced “electrospinning” with “electrospun fibers”, “3D printing” with “3D printed” bilayer membrane”, “Solvent casting method” with “Solvent cast nanocomposite films” in Table 1.

13. Conclusions: You wrote: “Due to the intricate dynamic … the selection of polymers and fabrication technique should be depended on specific requirements.” Do you have any indications of which material in what form would be desired in particular situation of burns or diabetic wound etc.? You wrote: “Nowadays, wound dressings are moving towards intelligent, personalized and high-end complex functions…. real-time monitoring…” can you add some examples from literature to support this statements?

A: Thank you very much for your valuable and prospective comments. We have re-searched the literatures and added some description and literatures in the conclusion section to address the reviewer’s questions as suggested. 

Reviewer 2 Report

The paper titled 'Recent advances of biodegradable and biocompatible synthetic polymers used in skin wound healing' by Ruojiao Xu et al. provides a comprehensive description of polymers that can be used in wound healing. However, despite being a review paper on polymers, Figure 2, which represents the polymer structures, contains numerous errors. While these may be minor mistakes, it is essential to rectify them as the paper focuses on the topic of polymers.

Figure 2:

The chemical formula of PCL (Polycaprolactone) is (C₆H₁₀O₂)n.

PLA is (C₃H₄O₂)n.

PLGA: (-CH₃) is missing

PU: I would recommend redrawing the structure of PU.

Minor

Line 52: Silk fibroin contain a great number of (Gly-Ala-Gly-Ser)n amino acid repeat -> Silk fibroin contains a great number of (Gly-Ala-Gly-Ser) amino acid repeat. "n" means repeating unit.

Line 435: "Cu2+/CS/PEG glycol films" should be corrected to "Cu2+/CS/PEG films." PEG stands for Polyethylene glycol.

The paper contains several grammatical errors (e.g., errors in subject-verb agreement, lack of article usage), which make it challenging to read.

Including follows:

Line 12: Defect skin -> defective skin

Line 36: endogenic healing system -> endogenous healing system

Line 93: hydrogels have become a considerable candidate for medical wound dressing in recently years -> hydrogels have become considerable candidates for medical wound dressing in recent years

Line 166: In this sentence, it would be more natural to use “Therefore” in terms of the flow.

Line 181: When using abbreviations, it is helpful to provide the full name when mentioning it for the first time to aid understanding.

Line 219: mechanical property ->mechanical properties

Line 246: sponge acts to hemostasis -> sponge acts to promote hemostasis

Line 267: make -> making

Line 313: rapidly manufacturer -> rapid manufacturing of

Line 322: Further -> Furthermore

Line 328: methods for hydrophilic modification of PLA scaffolds is needed - > are needed

Line 361: semi-permeable, which do not have -> semi-permeable, which means they do not have

Line 375: nature polymers -> natural polymers

Line 386: HIF-1a -> HIF-1α

 Section “Conclusion and future aspects”

Despite of the much achievements -> Despite of the many achievements

Author Response

1. Figure 2, which represents the polymer structures, contains numerous errors. While these may be minor mistakes, it is essential to rectify them as the paper focuses on the topic of polymers.

Figure 2:

The chemical formula of PCL (Polycaprolactone) is (C₆H₁₀O₂)n.

PLA is (C₃H₄O₂)n.

PLGA: (-CH₃) is missing

PU: I would recommend redrawing the structure of PU.

A: Thank you very much for your valuable and important comments! We apologize for the careless errors of the chemical formula. We have redrawed and corrected the mistakes of the chemical formula as suggested in Figure 2.

2. Line 52: Silk fibroin contain a great number of (Gly-Ala-Gly-Ser)n amino acid repeat -> Silk fibroin contains a great number of (Gly-Ala-Gly-Ser) amino acid repeat. "n" means repeating unit.

A: Many thanks for your careful check for our manuscript! We have removed the "n" from (Gly-Ala-Gly-Ser)n.

3. Line 435: "Cu2+/CS/PEG glycol films" should be corrected to "Cu2+/CS/PEG films." PEG stands for Polyethylene glycol.

A: Many thanks again. We have deleted the redundant word "glycol" at Line 442.

4. The paper contains several grammatical errors (e.g., errors in subject-verb agreement, lack of article usage), which make it challenging to read. Including follows:

Line 12: Defect skin -> defective skin

Line 36: endogenic healing system -> endogenous healing system

Line 93: hydrogels have become a considerable candidate for medical wound dressing in recently years -> hydrogels have become considerable candidates for medical wound dressing in recent years

Line 166: In this sentence, it would be more natural to use “Therefore” in terms of the flow.

Line 181: When using abbreviations, it is helpful to provide the full name when mentioning it for the first time to aid understanding.

Line 219: mechanical property ->mechanical properties

Line 246: sponge acts to hemostasis -> sponge acts to promote hemostasis

Line 267: make -> making

Line 313: rapidly manufacturer -> rapid manufacturing of

Line 322: Further -> Furthermore

Line 328: methods for hydrophilic modification of PLA scaffolds is needed - > are needed

Line 361: semi-permeable, which do not have -> semi-permeable, which means they do not have

Line 375: nature polymers -> natural polymers

Line 386: HIF-1a -> HIF-1α

 Section “Conclusion and future aspects”

Despite of the much achievements -> Despite of the many achievements

A: We are very grateful for the reviewer’s careful grammatical corrections for our manuscript. We have corrected all the grammatical errors as the reviewer suggested. In addition, we checked and corrected the gramma of the whole manuscript again to avoid other grammatical errors. Overall, we are very thankful for your valuable comments to help us correct and improve our manuscript.

Reviewer 3 Report

The aim of this review is clear and valid as the literature lacks in recent broader scope, yet concise overviews related to this field. The manuscript is generally well-written and thorough, however, I do not recommend it for publication (I request a minor revision) until the following issues are not resolved:

The manuscript needs a thorough grammar revision: mistakes such as “in recently years” (ln. 94.), “they have still limitations” (ln. 95-96), “nature polymers”, “despite of the much achievements” etc. can be found throughout the text.

The subchapters in chapter 2. are somewhat illogical and are not in accordance with the title of the chapter. For example: “Hydrogels” and “Foam and Sponge” are not fabrication techniques but different types of disperse material systems. The methods of hydrogel fabrication are entirely omitted from chapt. 2.1. (hydrogels can be prepared via e.g. 3D-printing, solvent-casting etc.), while the preparation of foams is somewhat discussed. Please, rethink the structure of the whole chapter and use a more systematic categorization scheme, e.g. categorize wound dressing according to their most notable physical properties (e.g. state of material). A conclusive table would also be more informative than the related Fig. 1.

Fig. 1. is also ambiguous as the possible polymer raw materials are seemingly paired with the different fabrication techniques. The figure also distinguishes (solid) foams and sponges, however, the literature uses these names interchangeably. Therefore, it would be important to clarify and highlight the differences between these two categories in the related subchapter (2.3.).

The Font size in Fig.3 and 4. is too low and the text is unreadable. Please, increase font size or split the figures into multiple parts for the sake of better visibility.

see previous section

Author Response

1. The manuscript needs a thorough grammar revision: mistakes such as “in recently years” (ln. 94.), “they have still limitations” (ln. 95-96), “nature polymers”, “despite of the much achievements” etc.

A：We apologize for the careless grammatical mistakes, and we have corrected them at Line 104 and 106 accordingly. In addition, we made a thorough gramma revision of the whole manuscript, which were labeled with blue color.

2. The subchapters in chapter 2. are somewhat illogical and are not in accordance with the title of the chapter.

For example: “Hydrogels” and “Foam and Sponge” are not fabrication techniques but different types of disperse material systems. The methods of hydrogel fabrication are entirely omitted from chapt.

3. (hydrogels can be prepared via e.g. 3D-printing, solvent-casting etc.), while the preparation of foams is somewhat discussed. Please, rethink the structure of the whole chapter and use a more systematic categorization scheme, e.g. categorize wound dressing according to their most notable physical properties (e.g. state of material).

A: Thanks very much for your valuable and helpful comments. We do agree with the reviewer’s comments and we reformatted chapter 2 and classified it according to the fabrication methods. Accordingly, we renamed the subtitle "hydrogel" to "hydrogel formation" to make it suitable for a fabrication method. In addition, we added the hydrogel fabrication techniques including template method, 3D printing, solvent casting, hydrogel self-assembly, etc in this section. Additionally, we agree with the reviewer that sponges and foams are not fabrication methods, but forms of prepared materials, and thus we deleted the section "Sponges/foams" in the revised manuscript. Furthermore, we added a new section “freeze-drying” in the text since it is also a frequently used method for wound patches production. Finally, we revised Figure 1 and checked throughout the manuscript and corrected the corresponding places. Overall, we are very thankful for your valuable comments to help us correct and improve our manuscript.

4. 1. is also ambiguous as the possible polymer raw materials are seemingly paired with the different fabrication techniques. The figure also distinguishes (solid) foams and sponges, however, the literature uses these names interchangeably. Therefore, it would be important to clarify and highlight the differences between these two categories in the related subchapter (2.3.).

A: We apologize for the misleading in the previous Figure 1. The reviewer is correct that the polymers should not be assigned to individual production methods. For clarity, we have revised Figure 1 and omitted the polymer part. Regarding the foams and sponges, they are not fabrication methods. Since we reformatted chapter 2 and classified it according to the fabrication methods, we therefore omitted foams and sponges from Figure 1 and deleted this section in the text on page 3.

5. The Font size in Fig.3 and 4. is too low and the text is unreadable. Please, increase font size or split the figures into multiple parts for the sake of better visibility.

A: Thanks very much for your valuable comments. For clarity, we have enlarged the font size in Fig.3 and 4 for the sake of better visibility.

Round 2

Reviewer 2 Report

Please check the chemical structures in figure 2 carefully.

Authors use -OH instead of =O for P for PCL, PLA, PLGA.

Author Response

1.Please check the chemical structures in figure 2 carefully.

Authors use -OH instead of =O for P for PCL, PLA, PLGA.

A:We apologize for the careless mistakes for the chemical structures in Figure 2. We have redrawed and corrected the mistakes in the revised manuscript. Many thanks for your careful checks for us!