Mechanical Properties of DNA Hydrogels: Towards Highly Programmable Biomaterials

Round 1

Reviewer 1 Report

The manuscript by Bush et al. reviews the recent developments in the field of DNA Hydrogels. I find this work timely as this field has recently gained significant attention and there are very few reviews available. This manuscript is well written, easy to follow and will help scientists evaluate whether this technique might be relevant for their research. I would be in favor of publication after this very minor comments are addressed:

• It would be beneficial if every technique presented would be represented by a figure. For example, in figure 2 there is no sketch for “Thermal responsive” or “Strand displacement”
• I find the discussion in section 6 quite short. Perhaps the authors could expand a bit more particularly regarding biomedical applications

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The manuscript is a topical short review on current knowledge about mechanical properties of DNA hydrogels, viewed as multi-scaled (bulk, micro and nano) supramolecular biomaterials with interesting (and even unique) physico-chemical properties. The main principles of structural design for pure and hybrid (nanocomposite) DNA gels are presented and discussed with focus on the structure - property relationships and the assets of programmability. Some of the methods/techniques for studying mechanical properties are briefly given, as well as examples of current biomedical applications. The authors aimed at supporting and promoting further research of these materials and development of new applications. The list of referrences covers recent publications on the topic, as well as late background items.

As a whole, this review article could be a good contribution to the current knowledge and research. Here are some comments and recommendations of mine:

1. There are unnoticed and missing items in the manuscript. The interplay of electrical and mechanical properties deserves to be included; at present, the usage of conductive DNA-based mechano-biosensors is "on the table". The current micro touch sensors, nano force sensors, DNA nanodevices and nanoactuators are also in the scope of the review. The hydration item (the liquid-holding capacity) is missed. The usual characterization methods are very good described, illustrated and discussed; however, the most "modern" method of AFM-based Nanoindentation is not even mentioned.
2. The following important articles are missed in the list of References: - Hale Bila, et al, Biomaterial Science, 2, 2019 (mini-review related to stability problem); - Jasin Kahn, et al, Acc Chem Res., 50(4), 2017 (about functionality principles and applications); - Zhongyang Xing, et al, PNAS, 115(32), 2018 (to microrheology of DNA hydrogels).
3. The Conclusion part simply rephrases the Abstract without outlining the challenges, most recent advances and current trends. As a result, the Conclusion does not rich the authors' aim as stated in the Abstract. In order to uplift the manuscript to the level of critical review article, I would recommend  revising and rewriting of this last, but essential part of the article.

 

 

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

This review article shows a comprehensive and well-organized overview of the current advances and mechanisms behind the creation and application of DNA hydrogels in the biomedical field, focusing on their mechanical properties and translating these to their applicability. 

Only a few minor comments to be introduced/fixed by the authors:

1. Despite being a well-known term, I would suggest introducing the definition of DNA as Deoxyribonucleic acid at the beginning of the introduction (line 26) and then use DNA from that point forward. 
2. In the introduction (lines 53-55), the authors mention the biomedical applications of DNA hydrogels. I would add immunomodulation-based approaches, specifically in vaccine development (along with a reference).
3. In section 2, subsection 2.1 (lines 87-88), I would encourage the authors to add a short statement with actual prices to provide the reader with an economic context for the claim.
4. In section 2, subsection 2.1. (lines 90-91), I would encourage the authors to add a range of quantities for production instead of just saying "milligram quantities" to provide the reader with numerical context. 
5. In section 6, lines 540-541, the authors mention "over other materials," and I would encourage them to add a short list or claim of these materials. 
6. As a general comment for section 6, I would encourage the authors to provide a few more examples in claims to provide strength to the entire section 6. 

Author Response

Please see attachment.

Author Response File: Author Response.pdf