Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review provides a timely and comprehensive overview of injectable hydrogel systems used for drug release, including both bulk hydrogels and particulate forms (microgels and nanogels). The manuscript is well structured and demonstrates good breadth, covering various administration routes (ocular, intra-articular, subcutaneous, intramuscular, tumor, central nervous system, and mucosal) as well as design considerations such as stimulus-responsiveness and manufacturing methods. The topic is highly relevant to both the biomaterials and pharmaceutical communities. However, although the manuscript is generally well written and informative, several aspects still require improvement before publication. These mainly concern the depth of analysis, the level of critical comparison, and the integration of materials science perspectives with translational considerations.

1.The review currently reads more like a broad survey than a critical analysis. While many fabrication methods and applications are listed, the authors should better highlight what is new, what key challenges remain unsolved, and which strategies show the most promise for clinical translation. A more critical comparison with other injectable systems would improve the originality of the review.

2.The discussion is heavily focused on biomedical application aspects, but less so on materials science fundamentals. For example, structure–property relationships (crosslinking density, polymer chain mobility, network topology) and their effects on injectability, degradation, and stimuli-responsiveness deserve more systematic discussion. Mechanical properties (elastic modulus, toughness, viscoelasticity) and how they correlate with tissue compatibility and injectability should be elaborated.

3.Figure 1 and Figure 2 are informative, but the review could benefit from a comparative table summarizing materials used, fabrication method, particle size range, advantages, and limitations in a side-by-side format. This would help readers quickly evaluate the suitability of each approach. Some figures are dense with text and would benefit from simplification or clearer labeling.

4.Although translational hurdles are mentioned, more detail is needed regarding scalability, reproducibility, sterilization, and regulatory approval pathways. These are essential to make the review useful for readers interested in practical application.

Comments on the Quality of English Language

Some parts require grammatical refinement.

Author Response

The authors sincerely appreciate the insightful and constructive feedback from the reviewer.

Please see the attachment for the point-by-point response. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

It is a very well-structured and discussed article about the use of injectable hydrogels for drug delivery. There are only minor points to address.

1) Being a review article, it is important to include more examples of injectable hydrogels by their site of application in Table 1.

2) It would be very helpful to include a diagram of the structure of the eye to see how it is formed and to be able to use it for the administration of hydrogels.

3) It would be very helpful to include a diagram of the structure of the eye to see how it is formed and to be able to use it for the administration of hydrogels.

4) In Table 2, include a column of the drugs that were formulated in the hydrogels

Author Response

The authors sincerely appreciate the insightful and constructive feedback from the reviewer.

Please see the attachment for the point-by-point response. 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript can be accepted.