The Use of Biomaterials in Three-Dimensional Culturing of Cancer Cells

Round 1

Reviewer 1 Report

The peer-reviewed article is about research on 3D cell culture with the addition of biomaterials.

This article is relatively well formatted with many references showing the progress. However, recent references are few and many works have been published. It is necessary that the authors add more recent references.

The listing of the different materials should be discussed and we should not only have a "catalogue" with a few characteristics. Schemes would also make it easier to understand and read. It is necessary to add a table or a figure mentioning all the materials listed by the authors.

Many minors corrections / additions are necessary to enhance the interest of this review:

- addresses 2, 3 and 6 are identical.

- the summary must be re-written because of repetitions in the lines.

- line 50 write "in vitro"

- line 96 "Hydrogel"

- "hydrogel part"; can be improve

- line 142 "650°C"

- line 143 "170°C to 400°C"

- in "3. Natural Polymer Hydrogels" ; it just looks like an enumeration without too much discussion.

- line 168; "RGD" define all acronyms

- line 169; "."

- line 224 "5. Applications"; introduce Table 1

- line 225; add structure of drugs in Table 1

- line 227 in "5.1.1. Drug Sensitivity"; add table

- line 232 "370°C"

- line 280 "in vitro"

- line 297;  "5.1.3. Viability" can be improve by adding table

- line 304 and 333 "2 weeks (14 days) and"

- line 309 "... the type of non-coalentic interactions formed by the matrix, the ..."; add scheme to explain

- line 311 and 340 the same "The hydrogel will act as a barrier for the diffusion transport of nutrients as well as certain 340 drugs in the formation of spheroids [82]."

- line 417 "6. Conclusions"; can be improve

- line 420 "in vivo"

- line 435 "References"; add very recent references (2021 and 2022)

- beware of many missing or extra spaces throughout the text (line 69, 85, ...)

Author Response

Dear Reviewer 1,

We thank you for your valuable critics and comments. Herewith, we try to answer your questions or revise the text according to your suggestions.

 

• This article is relatively well formatted with many references showing the progress. However, recent references are few and many works have been published. It is necessary that the authors add more recent references.
• Thank you for your suggestion, we have added more recent references accordingly.

• The listing of the different materials should be discussed and we should not only have a "catalogue" with a few characteristics. Schemes would also make it easier to understand and read. It is necessary to add a table or a figure mentioning all the materials listed by the authors.
• Thank you for the comment, we have added the table as suggested (in progress).

Many minors corrections / additions are necessary to enhance the interest of this review:

- addresses 2, 3 and 6 are identical. Fixed (deleting the repetition, hence the changed line number).

- the summary must be re-written because of repetitions in the lines.

- line 50 write "in vitro". Fixed

- line 96 "Hydrogel". Fixed

- "hydrogel part"; can be improve. Fixed

- line 142 "650°C". Fixed

- line 143 "170°C to 400°C". Fixed

- in "3. Natural Polymer Hydrogels" ; it just looks like an enumeration without too much discussion. Fixed with adding the point of why thechosen hydrogels.

- line 168; "RGD" define all acronyms. Fixed.

- line 169; "." Fixed

- line 224 "5. Applications"; introduce Table 1. Fixed.

- line 225; add structure of drugs in Table 1. Fixed

- line 227 in "5.1.1. Drug Sensitivity"; add table (in progress)

- line 232 "370°C". Fixed

- line 280 "in vitro". Fixed (in progress of a major revision)

- line 297;  "5.1.3. Viability" can be improve by adding table. (in progress)

- line 304 and 333 "2 weeks (14 days) and". Fixed

- line 309 "... the type of non-coalentic interactions formed by the matrix, the ..."; add scheme to explain (in progress)

- line 311 and 340 the same "The hydrogel will act as a barrier for the diffusion transport of nutrients as well as certain 340 drugs in the formation of spheroids [82]." Fixed.

- line 417 "6. Conclusions"; can be improve. Fixed (in progress)

- line 420 "in vivo". Fixed

- line 435 "References"; add very recent references (2021 and 2022). In progress.

- beware of many missing or extra spaces throughout the text (line 69, 85, ...) Fixed.

Reviewer 2 Report

This is an article with a good initial idea. It is focused on comparison of different types of hydrogels and how it may affect behavior of different cancer types. The topic of the article is very relevant, due to the increased interest of the scientific community in 3D tumor models. However, the article looks incomplete at the moment and requires a lot of improvements and corrections.

1) The article is hard to read through due to to high level of grammatical mistakes, so I recommend to revise the text. 

2) Title is confusing and do not reflect the main idea of an article properly

3) Introduction needs to have a clearer structure and a careful check of information included (especially lines 64-80)

4) The aim (lines 93-95) does not agree with the main body of the article

5)  Same with the conclusion

6) When discussing different types of hydrogels I recommend use same structure and same comparison criteria to make this section more informative. Moreover, there is no clear information explaining why each type of hydrogel is good in compare to others

7) In the "Application" part major revisions should be made. Firstly, there is no explanation why only lung and breast cancers were chosen. Secondly, I recommend to shorten each sub-paragraph and make information more defined. Moreover, there should be same structure and same comparison criteria to make it more vivid

Author Response

• This is an article with a good initial idea. It is focused on comparison of different types of hydrogels and how it may affect behavior of different cancer types. The topic of the article is very relevant, due to the increased interest of the scientific community in 3D tumor models. However, the article looks incomplete at the moment and requires a lot of improvements and corrections.
• We thank Reviewer 2 for the encouragement and the critics. We agree that the English writing needs a major revision and we are working hard on this subject.

1) The article is hard to read through due to to high level of grammatical mistakes, so I recommend to revise the text. 

Thank you, we are fully aware of this issue and are working hard to revise it.

 

2) Title is confusing and do not reflect the main idea of an article properly

Would "Biomaterials Used in Three Dimensional Culture of Cancer Cells" be more suitable?

3) Introduction needs to have a clearer structure and a careful check of information included (especially lines 64-80).

In progress of rewriting.

 

4) The aim (lines 93-95) does not agree with the main body of the article

5)  Same with the conclusion

6) When discussing different types of hydrogels I recommend use same structure and same comparison criteria to make this section more informative. Moreover, there is no clear information explaining why each type of hydrogel is good in compare to others

7) In the "Application" part major revisions should be made. Firstly, there is no explanation why only lung and breast cancers were chosen. Secondly, I recommend to shorten each sub-paragraph and make information more defined. Moreover, there should be same structure and same comparison criteria to make it more vivid

We thank your input and we hope that the second version of the draft would be easier to read and fulfill your requirements and corrections.

 

Due to the major revision of the writing, we hope that you would give us more time for submitting the file. However, we assure you that we are so eager and thankful for your initial review and therefore the second version of the draft is a given.

 

Round 2

Reviewer 1 Report

The authors having answered my questions and my proposals for additions, I therefore propose a publication of this article.

Author Response

We thank the reviewer for his/her constructive critics and suggestion. We hope that this revision would meet all the reviewer's requests.

 

Sincerely,

authors

Reviewer 2 Report

Unfortunately the article doesnt seem to be improved. The only thing which is good now - English . I still insist on some changes, which include restructuring:

When discussing different types of hydrogels I recommend use same structure and same comparison criteria to make this section more informative. Moreover, there is no clear information explaining why each type of hydrogel is good in compare to others

In the "Application" part major revisions should be made. Firstly, there is no explanation why only lung and breast cancers were chosen. The table makes everything more general and vivid now. Secondly, I recommend to shorten each sub-paragraph and make information more defined. Moreover, there should be same structure and same comparison criteria to make it more vivid

Author Response

We thank reviewer 2 for the constructive critics and suggestions. In the second round of revision, we have added some figures and hope this could help send a more straightforward message.

As to why only lung and breast cancers were chosen, it is because we would concentrate on working with those cancers (especially with patient-derived cells) in the future; we are developing herbal for those cancers, and because there are many patients with those cancers in our collaborative hospitals (although recent data also give a notion of colon cancer in rising). Thank you for the input, we are figuring out to put this explanation in the manuscript.

Sincerely,

authors