Micelle-Containing Hydrogels and Their Applications in Biomedical Research

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Current review article focus on the application of micelle loaded hydrogel for the biomedical research. Hydrogel is the one of the hot topic recently due to their unique properties of controlling drug release and biodegradability. Author try to cover many application relevant to micelle but still is wide topic.

Overall, article is written well and justified as much possible but still need improvement.

1)      Is it possible then cover the specific area such as cancer, wound and other disease and in that described available micelle loaded hydrogel formulation.

2)      In introduction section, formulation part is written down but not found in the article

3)      Kindly draw diagram of formulation of micelle and also hydrogel

4)      Highlight the what is drawback of micelle alone and which overcome using hydrogel

5)      Make a table of list of micelle loaded hydrogel and their application

6)      If any marketed formulation available then add in manuscript.

 

Author Response

Reviewer 1:

Current review article focus on the application of micelle loaded hydrogel for the biomedical research. Hydrogel is the one of the hot topic recently due to their unique properties of controlling drug release and biodegradability. Author try to cover many application relevant to micelle but still is wide topic.

Overall, article is written well and justified as much possible but still need improvement.

1)      Is it possible then cover the specific area such as cancer, wound and other disease and in that described available micelle loaded hydrogel formulation.

Thank you for the advice. In this short review paper, we focused on introducing micelle-containing hydrogel types and their representative applications in biomedical research. Please note that this is not a comprehensive review collecting the details. More importantly, as an emerging hydrogel material, up to now micelle-containing hydrogels have not been employed in many kinds of diseases. For more details of the corresponding applications, please see the newly added Table 1.

 

2)      In introduction section, formulation part is written down but not found in the article

The formulation of micelles has been described in the main text and now also been added to Table 1.

 

3)      Kindly draw diagram of formulation of micelle and also hydrogel

To make this paper more readable and have a broad readership, we chose to use cartoons to stand for the micelles and polymer chains within the hydrogels. The formulation of micelles has been described in the main text and now also been added to Table 1.

 

4)      Highlight the what is drawback of micelle alone and which overcome using hydrogel

Thank you for your suggestion. We have added the descriptions accordingly in Section 2, which now reads:

“Due to the instability, low local concentrations, and other issues of micelles in complex biological environments, directly using micelles as carriers for the sustained delivery of therapeutic agents still stays challenging [29], while loading micelles into the hydrogels can effectively address these issues for a broader application range in biomedical research and clinic.”

 

5)      Make a table of list of micelle loaded hydrogel and their application

Please see the newly added Table 1.

Micelle formulation	Category	Application	Reference
Resveratrol	Doped	Drug release	Joseph, A.; et al., 2022 [32]
PIPAAm	Doped	Thermo sensor	Yoshida, R.; et al., 1995 [34]
Cholesterol-hyaluronate	Doped	Contact lens	Mun, J.; et al., 2019 [6]
Modified PEG	Chemically crosslinked	Drug delivery	Sawhney, A. S.; et al., 1993 [17]
PU	Chemically crosslinked	Memory material	Tan, M.; et al., [43,44].
UPy	Chemically crosslinked	Cell encapsulation	Qin, Z. et al., 2019 [49]
Pluronic F127	Physically crosslinked	Memory material	Yang, H.; et al., 2022[54]
CDAB	Physically crosslinked	Strain sensor	Khan, M.; et al., 2023 [55]
PEG-PLA	Physically crosslinked	Lacrimal implant	Zhao, J.; et al., 2023 [56]
SDS	Physically crosslinked	Gas therapy	Zhou, X.; et al., 2023 [63]
SDS	Physically crosslinked	Drug release	Zhou, X.; et al., 2023 [64]
SDS	Physically crosslinked	Soft robotics	Tao, L.; et al., 2021 [65]
PEO-PPO-PEO	Chemically crosslinked	Drug delivery	Zhao, L.; et al., 2011 [70]
F127 and SPION	Physically crosslinked	Drug release	Qin, J.; et al., 2009 [71]
Liposome	Physically crosslinked	Drug release	Correa, S.; et al., 2022 [73]

 

6)      If any marketed formulation available then add in manuscript.

The information has been added accordingly to the main text as well as Table 1.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Author,

Your manuscript entitled “Micelle-containing Hydrogels and Their Applications in Biomedical Research” has been comprehensively evaluated. Although the manuscript was well designed and the topic was wisely selected, there was a need for a generation of better manuscript. Thus, minor revisions were requested to address some of the conflicts. Hereby, I would like to present my comments.

1. Please give information about the selection of the studies in your manuscript. Which databases were scanned? Was there a specific period scanned (e.g. last 20 years?) What was inclusion or exclusion criteria when selecting the literature data? Please clarify this issue.

2. 2.2.1. Chemically crosslinked micelle hydrogels section, line 157: …hydrogels with unique properties [40].” Please give examples about “the unique properties” (such as controlled release, pH stimulated release etc.).

3. Grammar should be checked meticulously. (e.g. line 208: …was report recently.)

4. 2.2.2. Physically crosslinked micelle hydrogels section, line 227: F127? Is it Pluronic 127? please give at least one explanation in the first place of usage.

5. (As a suggestion) 4. Micelle-containing hydrogels as delivery systems section: Please make a comprehensive literature search based on the pharmacological action or route of application (anticancer activity or ophthalmic route). Then, please share your findings in a summarized table.

6. The references section should be carefully monitored. The journal names should be abbreviated as indicated in the instructions for authors. (e.g. REF11,12,19,29,52,66,70)

Best regards.

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Author Response

Reviewer 2:

Your manuscript entitled “Micelle-containing Hydrogels and Their Applications in Biomedical Research” has been comprehensively evaluated. Although the manuscript was well designed and the topic was wisely selected, there was a need for a generation of better manuscript. Thus, minor revisions were requested to address some of the conflicts. Hereby, I would like to present my comments.

1. Please give information about the selection of the studies in your manuscript. Which databases were scanned? Was there a specific period scanned (e.g. last 20 years?) What was inclusion or exclusion criteria when selecting the literature data? Please clarify this issue.

Thank you for the comments. The literature we cited is selected based on the content, and thus there was no specific timeline limit or database restriction. Briefly, we chose representative and topic-related studies from mainstream journals. In this short review, we focused on the introduction of micelle-containing hydrogel types and their representative applications in biomedical research. Please note that this is not a comprehensive review collecting the details or meta-analysis.

 

2. 2.2.1. Chemically crosslinked micelle hydrogels section, line 157: …hydrogels with unique properties [40].” Please give examples about “the unique properties” (such as controlled release, pH stimulated release etc.).

The statement has been revised accordingly, which now reads:

“This technique has been frequently used to prepare tough hydrogels with unique mechanical properties [42].”

 

3. Grammar should be checked meticulously. (e.g. line 208: …was report recently.)

Thank you for your careful reading. We have made the revisions accordingly.

 

4. 2.2.2. Physically crosslinked micelle hydrogels section, line 227: F127? Is it Pluronic 127? please give at least one explanation in the first place of usage.

Thank you for the comments. We have made the revisions accordingly, which now reads:

“Another example is Pluronic F127 diacrylate (F127DA)-based micelle hydrogels, which was synthesized by acrylating the end hydroxyl groups of Pluronic F127 using acryloyl chloride and triethylamine.”

 

5. (As a suggestion) 4. Micelle-containing hydrogels as delivery systems section: Please make a comprehensive literature search based on the pharmacological action or route of application (anticancer activity or ophthalmic route). Then, please share your findings in a summarized table.

Thank you for the suggestion. Please see the newly added Table 1.

 

6. The references section should be carefully monitored. The journal names should be abbreviated as indicated in the instructions for authors. (e.g. REF11,12,19,29,52,66,70)

Thank you for the careful reading. The citations have been revised accordingly.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The revision is satisfactory.