Synthesis of Hydrogel-Based Microgels and Nanogels Toward Therapeutic and Biomedical Applications

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Report of the manuscript titled "Synthesis of Hydrogel-Based Microgels and Nanogels toward Therapeutic and Biomedical Applications" and submitted to Applied Science.

The review focuses on hydrogels, a versatile biomaterial known for its biocompatibility, chemical and physical tunability, and adaptability to various fabrication techniques. A key advancement discussed is the use of micro/nanofabrication technologies that leverage the unique properties of hydrogels, along with interdisciplinary approaches, to create innovative systems at small scales. The review provides a comprehensive summary of recent progress in fabricating hydrogel-based micro- and nano-systems, particularly highlighting their applications in biomedical and therapeutic fields. It also examines the challenges and future opportunities in material selection, fabrication processes, and system design for developing effective, personalized, and adaptable hydrogel-based therapies.

The manuscript is complete and interesting, as demonstrated by its length and the number of references cited. However, there are two aspects that, in my opinion, deserve improvement:

1. Among the biomedical applications of synthetic hydrogels, gel dosimetry is certainly noteworthy. It would be beneficial to add a paragraph on this topic. Below, I am providing a few manuscripts that the authors may consider, although this list is by no means exhaustive (10.3390/gels10030172, 10.1088/1361-6463/ad0987, 10.1016/j.apradiso.2023.110827, etc).
2. The section “3.3.1. Condensation Reaction” could be enhanced by discussing its limitations.

Additionally, I suggest reviewing the English language throughout the manuscript. While it is very clear, there are instances where it is unclear whether the authors are using British or American English.

I look forward to reviewing the updated version of the manuscript.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The paper summarizes interesting and relevant results but requires substantial improvements before it can be considered for publication.

The authors should clearly outline the advantages and disadvantages of nano- or micronanogels compared to traditional hydrogels.

The title of subsection 2.1.1 "Acrylamide" should be revised to "2.1.1 Acrylamide and Its Derivatives."

Examples presented in Subsection 2 should be further organized into a table format, detailing the hydrogel chemistry, synthesis methods, applications, and relevant references.

In Subsection 2.3 "Hybrid Hydrogels," information on their chemical structure is entirely missing. Given the diversity of this hydrogel group, representative examples illustrating their structures should be included.

In Subsection 4 "Paradigm Shift: Bulk Hydrogels to Hydrogel Micro/Nanoparticles," the authors focus on designing stimuli-responsive properties of nanogels, which is certainly important. However, this is not the only future challenge. Consider discussing additional aspects such as enhanced biocompatibility and interactions with biological systems.

The paper contains minimal information on multifunctional systems, such as multi-responsive hydrogels. It would be beneficial to reference studies such as: https://doi.org/10.1021/acsbiomaterials.3c00917

https://doi.org/10.1021/acsami.2c20395

Finally, although the paper's title refers to "therapeutic and biomedical applications," no separate subsection specifically discusses biomedical uses, such as applications in tissue engineering. Including such a section would significantly enhance the paper's relevance and coherence.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The quality of the review was strongly improved. I recommend accepting review in the present form.