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Article
Peer-Review Record

Biocompatibility Analysis of GelMa Hydrogel and Silastic RTV 9161 Elastomer for Encapsulation of Electronic Devices for Subdermal Implantable Devices

by David Catalin Dragomir 1,2, Vlad Carbunaru 3,*, Carmen Aura Moldovan 1, Ioan Lascar 3,4, Octavian Dontu 2, Violeta Ristoiu 5, Roxana Gheorghe 5, Ana Maria Oproiu 3,4, Bogdan Firtat 1, Eduard Franti 1,6, Monica Dascalu 2,6, Tiberiu Paul Neagu 3,4, Dan Mircea Enescu 4, Octavian Ionescu 1,7, Marian Ion 1, Carmen Mihailescu 1, Ruxandra Costea 8, Magda Gonciarov 8, Gabriela Ionescu 7, Adrian Dumitru 4, Anca Minca 4, Catalin Niculae 9, Stefania Raita 8, Ioana Rosca 4, Sorin Lazarescu 4, Cristian Stoica 4, Raluca Ioana Teleanu 4 and Daniel Mihai Teleanu 4add Show full author list remove Hide full author list
Reviewer 1: Anonymous
Reviewer 2:
Submission received: 16 November 2022 / Revised: 14 December 2022 / Accepted: 15 December 2022 / Published: 22 December 2022

Round 1

Reviewer 1 Report

The manuscript is quite interesting, but needs to be revised. 

There is a strong imbalance between everything you say you have done and the results discussed. 

In the results, there is no verification of the efficacy of GelMA synthesis or its encapsulation. 

You say you have performed these processes, but there is a lack of experimental evidence to confirm this. 

In fact, the results and discussion are poor because this part is missing. 

In the results, it also seems strange to me to see 'cell viability' values with two decimal places. 

The microscope photos are all before markers and it is not clear from the description which parts you are referring to, so you need to improve the description

 

Author Response

Thank you for the reviewers’ comments concerning our paper entitled “Biocompatibility analysis of GelMa Hydrogel and Silastic RTV 9161 Elastomer for encapsulation of electronic devices for sub-dermal implantable devices”. All comments are valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research. Now, we are submitting the revised version after seriously considering the comments of the Reviewers. We hope that this version will improve the quality of our manuscript and make it more acceptable for publication.

On behalf of my co-authors, I would like to clarify some of the points brought up by the Reviewers. We hope that the Reviewers and the Editor will be satisfied with our replies to the comments and our manuscript.

Author Response File: Author Response.pdf

Reviewer 2 Report

Some specific comments are as follows:

Page 2, Line 65, “cultivated cell condition in vitro”…………………………Please mention the cell line name that will be used in the present study.

Page 2, Line 66, “in a living animal for 21 days and the extracted samples”…………………..What is the name of animal used? , samples are not extracted but you could refer to the selected tissue samples used in the histopathology technique.

Page 2, Lines 72-74 “by adding methacrylic anhydride in a 10% (w/v) suspension of gelatin in phosphate buffer at a rate of 0.5 mL/min under steady stirring.”…………….. This is not clear, adding methacrylic anhydride to what? To Gelatin in phosphate buffer 10%? Please clarify.

Also, please state the name of the manufacturer and city from where all used chemicals, equipment/instruments were sourced.

Please correct degrees in all the text to …………….℃

Page 2, Line 78, integration of LAP Photoinitiator………….this step is not clear, please clarify it more.

Page 2, Line 86, “The proposed elastomer RTV 9161 silicone rubber it’s a suitable material”…. The proposed elastomer RTV 9161 silicone rubber is a suitable material.

Page 2, Subtitle. Medical silicone. It is not clear… did you purchase them fully prepared, or authors prepared them by adding silicone rubber with catalyst?

Also, the properties of the medical silicone could be added in the introduction or within the discussion part if needed but not in the methodology part.

Page 3, Line 108, “needs to function is a sterilized medium”…… needs to function in a sterilized medium, sterilized area, or media? What medium?

Page 3, Line 110, In order to ensure that the medium is clean…….What do you mean by medium? The surrounding area? Please clarify.

Page 3, Line 110, “0.1 mm to 0.5 are fitted (fig. 1)”……… 0.1 to 0.5 mm are fitted (fig. 1).

Page 3, Line 111, After the material has been loaded into the syringe……..What material?

Page 3, Line 113, pneumatic pressure……Mention the pressure value and unit.

Page 4, in Figure 1. It will be good to add arrows on the figure showing labels that are mentioned within the text of bioprinter such as extruder, syringe, printing house, the printing bed and the printhead, ……etc.

Page 4, Line 144, is has been soaked in a ionic crosslinking solution…….it has been soaked in the crosslinking solution (mention this solution).

Page 5, Line 155, The materials were washed with sterile PBS………..specify the name of referred materials.

Page 5, Line 157, Mention the source of your cells. Also, mention that different groups were conducted in triplicate because author refer in Biocompatibility in vitro results n=3.

Page 5, Line 183, implanted in a sous scrofa subject to the experiment…….., implanted in a Sus scrofa.

What is the age, gender, need more information about used animal.

Page 5, Line 185, All procedures had been approved by the Faculty of Veterinary Medicine Ethics Committee………………What is the approval number and date? Refer here.

Page 5, Line 188, were surgically extracted………….. Please clarify this point….the devices were surgically extracted with the surrounding biological tissue for sectioning. The volume or approximate weight of the surrounding tissue used in fixation, embedding and sectioning . Before surgery, how did you kill the animal?

This part about histopathological technique needs reference.

Page 6, Line 210 & 211,  Day 3: Control conditions, Day 6: Control conditions……..correct to …….control untreated cells.

Page 6, Figure 4, control group……more accurate to write……control (untreated cells).

 Page 6, Figure 4, Gelma…………correct to……….. GelMA

Within the whole text, Control conditions……..correct to …….control untreated cells.

Page 7, Line 228, x20 and x40 zoom……………….it is not a zoom, correct to x20 and x40 magnification.

Figure 5. also correct the legend to magnification instead of zoom and add the scale value at the end of the legend. Also, the scale bar on the figure hard to be seen.

Page 7, Line 229, frequent macrophages, histiocytes and lymphocytes around fragments…….Add arrows, star, or lines on the related figure 5 to show those stated cells.

Page 8, Figure 6, correct the legend to magnification instead of zoom and add the scale value at the end of the legend. Also, the scale bar on the figure hard to be seen.

Page 8, Line 249, He stain…………………HE stain.

Page 9, Lines 255-279………………..Where are the references of those paragraphs?

The present results show high toxicity of the experimental materials in vivo and in vitro…..what is your discussion in this important point, is there mechanism for this toxicity, previous work in agreement to this work. In page 2, author state that “The proposed elastomer RTV 9161 silicone rubber it’s a suitable material that has medical grade appliances.” It is safe for use…..What is your comment on their toxicity? I didn’t find any explanation.

The author needs to discuss their results according to previous work, The discussion part is too poor in this, it should be rewritten in detail.

It is a good topic but Is it within the journal scope?

References are very few and not updated, the most recent references are 2017, the article needs more recent updated references.

- In the current state, there are more typographical errors. Few sentences need to be rewritten in more clear form with complete information, especially in the methodology. Therefore, the authors are advised to recheck the whole manuscript for improving the language and structure carefully.

Best

Author Response

Thank you for the reviewers’ comments concerning our paper entitled “Biocompatibility analysis of GelMa Hydrogel and Silastic RTV 9161 Elastomer for encapsulation of electronic devices for sub-dermal implantable devices”. All comments are valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research. Now, we are submitting the revised version after seriously considering the comments of the Reviewers. We hope that this version will improve the quality of our manuscript and make it more acceptable for publication.

On behalf of my co-authors, I would like to clarify some of the points brought up by the Reviewers. We hope that the Reviewers and the Editor will be satisfied with our replies to the comments and our manuscript.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

no other comments

Author Response

Thank you for the reviewers’ comments concerning our paper entitled “Biocompatibility analysis of GelMa Hydrogel and Silastic RTV 9161 Elastomer for encapsulation of electronic devices for sub-dermal implantable devices”. All comments were valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research.

Reviewer 2 Report

Second review:

Most of the comments are done and corrected by the authors

But few specific comments are as follows:

Page 2, Line 71

and the selected tissue……………………….. and then the selected tissue samples around the implanted devices were used in the histopathological technique.  

Page 3, Line 111

0.1 to 0.5 mm are fitted are fitted (fig. 1)………………………. 0.1 to 0.5 mm are fitted (fig. 1)

Page 9 Line 276

ad-verse effect…………………………..adverse effect

Page 9 Line 288

can deteriorates theits performance…………………………. can deteriorate their performance

 Page 9 Line 291

and cell integra-tion………………………………… and cell integration

Page 9 Line 292

Noshida……………………Noshadi

 

Page 9 Line 292

[15]………………. [15].

Page 9 Line 297, 298, 300, 301, 303…………….correct

long-term im-plantation……………………… long-term implantation

the me-chanical and biological that simulates ……………correct…….the mechanical and biological that simulates ………………..

mechanical and biological???? what

GelMA encapsu-lation……………….. GelMA encapsulation

cell adhe-sion……………………………. cell adhesion

mechani-cal……………………… mechanical

Page 10 Line 342

mechanical proprieties………………… mechanical properties

Page 10 Line 343

26 ℃but…………………..26 ℃ but

Correct the newly added references according to the guideline of the journal

Finally, I suggest adding coatings within the text (not the conclusion only) to make your article related to the coatings journal and within scope.

Good work

best regards

Author Response

Thank you for the reviewers’ comments concerning our paper entitled “Biocompatibility analysis of GelMa Hydrogel and Silastic RTV 9161 Elastomer for encapsulation of electronic devices for sub-dermal implantable devices”. All comments were valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research.

Author Response File: Author Response.docx

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