Nanostructured Hydrogels: A Method to Prevent Biofilms on Implantable Medical Devices
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThis review shows an overview of how nanostructured hydrogels prevent biofilms. The authors mainly focused on the methods for producing nanostructured hydrogels, their current status, and associated challenges etc. The corresponding methods are also clearly and systematically summarized. This review is very interesting, which could provide theoretical guidance for preventing biofilms. In my opinion, this review could be accepted for publication in gels after addressing the following points.
1.The abstract should be revised carefully to highlight the main methods for fabricating nanostructured hydrogels and the corresponding mechanisms.
2.Some sentences are long and complex, please check and revise them to improve the readability, e.g. lines 179-181 and lines 444-447.
3.The authors should also point out the limitations of nanostructured hydrogels.
4.Add more discussion about the mechanism in each part.
5.Pay attention to some polysaccharide-based hydrogels that could prevent the formation of biofilm, e.g. https://doi.org/10.1016/j.ijbiomac.2025.145899, https://doi.org/10.1016/j.ijbiomac.2025.142598, https://doi.org/10.1016/j.ijbiomac.2025.144496, https://doi.org/10.1016/j.ijbiomac.2024.136647
Author Response
Response: Thank you. We thank the reviewer for the insightful comments. We have addressed the concerns as follows.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsThis manuscript provides a comprehensive narrative review of biofilm formation on medical devices and evaluates nanotopographical surface engineering—particularly nanostructured hydrogels—as a non-antibiotic strategy to prevent microbial adhesion and biofilm development. Its main contribution is synthesizing literature on surface nanotopography–microbe interactions and highlighting the underexplored potential of static and dynamic nanopatterned hydrogels for antibiofouling biomedical applications.
Here are my comments:
The manuscript does not sufficiently articulate what is new relative to existing reviews. Several cited reviews already address nanotopography–biofilm interactions and antibiofouling surfaces. There is no explicit comparison table or conceptual framework distinguishing nanopatterned hydrogels from nanopatterned rigid substrates.
The manuscript treats “biofilms” largely as a uniform phenomenon. Important distinctions between Gram-positive vs. Gram-negative bacteria, fungal biofilms, and polymicrobial biofilms are mentioned but not systematically analyzed.
Several important cross-disciplinary literatures are missing, like Machine learning-enhanced soft robotic system inspired by rectal functions to investigate fecal incontinence.
Surface stiffness is mentioned sporadically, but not integrated into the main argument. No discussion of how substrate modulus alters bacterial mechanosensing or membrane stress.
Include a table summarizing reported nanopatterned hydrogel systems such as polymer type, feature size, fabrication method, tested organism. Clearly distinguish what is proven vs. what is hypothesized for hydrogels.
The conclusions are largely descriptive and do not prioritize research directions. No concrete experimental roadmap is proposed.
Author Response
Response: We appreciate the constructive comments. We have addressed your comments as follows.
Author Response File: Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for AuthorsIt is very interesting that authors conducted the review on the methods for nanostructured hydrogels to prevent biofilms on implantable medical devices. My comments are given as follows:
1. Suggest the authors to use a flowchart or a diagram to clearly describe the strategies which are employed to prevent the formation of biofilm.
2. The authors showed incorporation of nanoparticles to prevent the formation of biofilm, it may be better to use a morphological demonstration of this mechanism.
3. In Section 4, the authors showed different methods to prevent the formation of biofilm. However, I did not see the clear statements of the disadvantages or shortages of those methods.
4. Section 5 showed hydrogels are developed as biomaterials especially the fabrication of surface-patterned hydrogels. Suggest the authors to use figures or images to clearly show the different methods visually and clearly. Also, would like to see a table to compare the difference of mechanical properties between patterned hydrogel and other hydrogels/biomaterials.
It is just my own opinion that the current manuscript may be not suitable for being considered for a publication before all raised comments being addressed in detail.
Author Response
Response: We are grateful for Reviewer 3's comments and have addressed them in the cover letter.
Author Response File: Author Response.pdf
Round 2
Reviewer 2 Report
Comments and Suggestions for Authorsok with this version
Reviewer 3 Report
Comments and Suggestions for AuthorsThe authors already addressed all raised comments in detail. Therefore, I don't have any further scientific queries.
