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Peer-Review Record

NaHS-Hydrogel and Encapsulated Adipose-Derived Stem Cell Evaluation on an Ex Vivo Second-Degree Burn Model

by Lucille Capin 1,2,3,*,†, Olivia Gross-Amat 1,2,3,*,†, Marie Calteau 2, Marie-Rose Rovere 2, Damien Salmon 4 and Céline Auxenfans 2,5
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3:
Submission received: 6 January 2021 / Revised: 7 February 2021 / Accepted: 15 February 2021 / Published: 19 February 2021

Round 1

Reviewer 1 Report

It's a good idea to evaluate the effect of NaHS, a hydrogen sulfide (H2S) donor, in poloxamer hydrogel in topical application and the potentiating effect of injected encapsulated adipose-derived stem cells (ASCs) compared to monolayer ASCs using our previous second-degree burn model on human skin explants. In this paper, the authors emphasized that the benefit of encapsulated adipose-derived stem cells (ASCs) on epithelial cell proliferation and wound healing processes.I would like to ask a few questions, which would be great if it can be addressed.

 

  1. It would be great if we can evaluate the capacity of ASC before the transplantation. It would useful to compare both MO and EN ASCs, the number of cells, the capacity of proliferation, et al.
  2. How many human samples were included in this study, a statistic significant with three separate experiments are required for the result analysis and conclusion.
  3. It’d also be a good idea to look at the relationship between proliferation and senescence, which may happen and explain the interesting results you find on day 10 and day 15, regarding the thickness and keratinocytes proliferation difference.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear authors,

the work entitled “NaHS-hydrogel and encapsulated Adipose-derived stem cells evaluation on an ex-vivo second degree burn model” appears very well structured and written.

Just a couple of comments related to some concept and issues need to be addressed.

The work aims to resolve some doubts related to the effect of NaHS in poloxamer hydrogel in topical application and on the possibility to use encapsulated adipose-derived stem cells (ASCs) as a method to potentiate the effect in wound healing applications, in particular adopting a second degree burn model.

Anyway, on page 3, lines 122-124, the authors declare “The addition of NaHS to the poloxamer hydrogel did not alter the gel consistency or jellification point of the gel. No difference was observed between poloxamer hydrogel and NaHS-poloxamer-hydrogel.”  Have the authors conducted some experiments in this regard? Have the authors quantified, i.e., the values of G’ and G’’ over frequency or evaluated the viscosity vs shear rate? (see for example, Tunesi et al, NPG Asia Materials 2019; Russo et al, Proc Inst Mech Eng H 2015).

Regarding Encapsulation of ASCs in Alginate, it is not clear whether the authors intend to use these microbeads alone or incorporated in the poloxamer gel. The authors could indicate some issues about the microparticles’ concentration adopted (whether they are injected alone or incorporated into the gel), the system adopted for the injection (i.e., needle dimension) and the injection rate. Furthermore, after the injection, viscoelastic properties of injectable gels may decrease. Micro- or nano-particles eventually embedded could act as a reinforcement at a specific concentration, acting on the values of both dynamic moduli and making hydrogel systems still suitable for the specific application. The optimization of injectable nanocomposites and the prediction of their mechanical behavior represent a great challenge, which may be faced by suitably integrating experimental rheological tests with mathematical models (see for example Giordano et al, Int J Artif Organs 2011).

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

I believe that the manuscript will be very interesting for readers of the EBJ since it presents powerful ex vivo burn model and uses it to test 2 potential improvements to treatment. I find the results convincing and informative. I propose an improvement of contrast in some figures, such as Figure 4 where even the brightest panel is very dim. Figure legends do not always include full information on staining. E.g. blue is missing in the supplementary material and is presumably the same as Figure 4.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

I am ok with current version

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