Biotechnology Applied to Cosmetics and Aesthetic Medicines

Round 1

Reviewer 1 Report

The work addresses a topic that has become important in recent years, only having the last 10 years, the number of papers published each year has been doubled, during the year 2018 and 2019 more than 200 articles were published. The work is well written and very easy to read. However, this work could well be considered a “mini review”. It lacks depth, good for an introduction to the topic,

Practically all sections of the work require an extension, sections 1, 2, 3 and especially 4 including some other compounds that are also of interest in industrial cosmetics.

Update the literature using references from 2018-2020.

 

 

Author Response

Point 1: Practically all sections of the work require an extension, sections 1,2,3 and especially 4 including some other compounds that are also of interest in industrial cosmetics.

Response 1: We appreciate your suggestion and for that, several paragraphs have been added in order to deepen the issues covered in sections 1, 2, 3 and especially in section 4. All changes are highlighted in the manuscript. Due to the length of the added text it is not possible to detail all changes in this cover letter.

 

Point 2: Update the literature using references from 2018-2020.

Response 2: References from 2018-2020 were added, namely the references 2, 4, 9, 11, 20, 34, 42, 46, 56, 62, 63, 71, 76, 78, 80, and 82.

Author Response File: Author Response.docx

Reviewer 2 Report

I think biotechnology could cntribute to cosmetics, same as you. but, the issues you mentioned are only potential, not real.

Authors confused cosmetics with cosmetic medicine. cosmetics are safe commercial products for everybody. 

Threfore, your article is "introduction of biotechnorogies that may be used for cosmetics and cosmetic medicines". furthermore, some of you mentioned can not be used as cosmetics ingredients at now.

for example, growth factors should be only for medicines not for cosmetics. those are very effective, it means everybody can not be used to avoid serious side effects. the normal cosmetics should be used by everybody, must be safe to use.  it may be use as medicine, not cosmetics.

the enzymes are very careful ingredients for cosmetics. as you know, enzymes are protein, it means protein has a ptential for allergies. when those ingredients you mentioned are used, there are only noticeable risks. even if those are used in the field of cosmetic medicines, safety and effectiveness must be  evaluated more and more. I think the most easy way to use enzyme is to use for production of the cosmetics ingredients. there are many examples for such productions, glucose and other sugars, fatty acids and their derivertives, and some aminoacids. please consider again.

stem cells are used now at the medical area including beaty purpose. It cannot be used as general cosmetic products.

as above shown, please consider again.

 

 

Author Response

Point 1: Authors confused cosmetics with cosmetic medicine (…).Therefore, your article is “Introduction to biotechnologies that may be used for cosmetics and cosmetic medicines” furthermore some of you mentioned can not be used as cosmetics ingredients at now. for example, growth factors should be only for medicines not for cosmetics. those are very effective; it means everybody cannot be used to avoid serious side effects. the normal cosmetics should be used by everybody, must be safe to use.  it may be use as medicine, not cosmetics. The enzymes are very careful ingredients for cosmetics. as you know, enzymes are protein, it means protein has a potential for allergies. when those ingredients you mentioned are used, there are only noticeable risks. even if those are used in the field of cosmetic medicines, safety and effectiveness must be  evaluated more and more. I think the easiest way to use enzyme is to use for production of the cosmetics ingredients. there are many examples for such productions, glucose and other sugars, fatty acids and their derivatives, and some aminoacids. please consider again. Stem cells are used now at the medical area including beaty purpose. It cannot be used as general cosmetic products.

 

Response 1: Thank you for your comment. All ingredients described in the manuscript (including the growth factors, enzymes and plant stem cells) can be used in cosmetic products, according to credible bibliographic sources, based on peer-reviewed publications.

Reviewer 3 Report

Attached PDF contains comments throughout.

In general:

Many of the references were not utilized in a good way: the manuscript offers a very general statement backed by a reference that discusses a highly relevant topic that should have been discussed in more detail within the manuscript. Many of these references do not appear to be citing the actual research, but just a line or a phrase from the source. 

The references have major potential to make this a much stronger, more interesting, and more relevant to the current field.

Comments for author File: Comments.pdf

Author Response

Point 1: Many of the references were not utilized in a good way: the manuscript offers a very general statement backed by a reference that discusses a highly relevant topic that should have been discussed in more detail within the manuscript. Many of these references do not appear to be citing the actual research, but just a line or a phrase from the source. The references have major potential to make this a much stronger, more interesting, and more relevant to the current field.

 

Response 1: We are grateful for your comments and appreciate your suggestions. The alterations that have been made are underlined in yellow in the manuscript.

 

Line 68. A reference was made regarding insulin produced using E. coli as a host.

 

Line 77.The following sentence was added: “Bioreactors can also be widely used to culture plant cells for the large-scale production of recombinant proteins, secondary metabolites and cosmetic ingredients [2]”.

 

Line 144. The following paragraph was added: “Nanodelivery systems, such as polymeric nanoparticles and liposomes, have been studied to transport KA through the skin in order to inhibit the synthesis of melanin. There are already some commercial cosmetics products containing KA, including lotions, creams and soaps [20]”.

 

Line 154. The following paragraph was added: “When HA networks are strengthened, due to increased molecular weight and concentration, HA solutions increase viscosity and viscoelasticity. These properties allow the HA molecules to be used in cosmetics to restore hydration and elasticity, while improving the skin’s appearance [34]”.

 

The Table 1. “Growth factors used in cosmetic products and respective functions” has been removed from the manuscript and changes were made in Table 2. "Topically used peptides", now designated Table 1.

 

Line 226. The following paragraph was added: “When E. coli is used as host, the yield is not appropriate for industrial requirements, as the hEGF cytoplasm tends to form inclusion bodies, which can be rapidly degraded by proteases. Thus, the total production cost ends up increasing due to the additional production steps required to release hEGF from inclusion bodies. In addition, the hEGF produced by prokaryotic systems is lower compared to that produced by eukaryotic systems. Therefore, the use of eukaryotic systems, such as P. pastoris, can produce the growth factor on a large scale [51]”.

 

Line 249. The following paragraph was added: “SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species (formed through UV exposure and other radiation, as well as from normal cellular metabolism), limiting the potential toxicity of these molecules and controlling cellular aspects that are regulated by their signaling functions [56]”.

 

Line 260. The following paragraph was added: “By promoting exfoliation, these proteases will improve the appearance of the skin. Bromelain, papain and chymotrypsin are the examples of herbal proteases used in cosmetics, but cannot be used by most individuals, due to the risk of allergy [16]”.

 

Line 270. The following paragraph was added: “Navarrete-Dechent and Molgó performed a clinical study to evaluate the usefulness of a new topical sunscreen containing DNA photolyase for the treatment of actinic keratoses. The cream used was applied twice a day for three months. (…) Marizcurrena et al. produced a bacterial recombinant photolyase from Hymenobacter sp. UV11, and did the characterization of its DNA repair ability. So, an enzyme was easily produced in a host cell and showed potential UV-damaged DNA repair activity in vitro. This work showed that the results obtained could contribute to the development of cosmetic products containing photolyases [62]”.

 

Line 286. The sentence has been rewritten: “Significant advances have been made in microalgae biotechnology, with microalgae suspensions cultures being used to produce recombinant proteins and other valuable ingredients, that can be used in cosmetics [64]”.

 

Line 289. The following paragraph was added: Maia Campos et al. developed some preliminary studies and showed antioxidant potential, skin compatibility and immediate effects on the skin hydration with formulations containing Spirulina extract obtained by biotechnological processes [66].

 

Line 321.  The following sentence was added: “Many companies scaled up the production of stem cells from in vitro cultures to bioreactors that are used on a large scale”.

 

Line 351. The following paragraph was added: “This compound allows cells to remove the excess of free radicals to protect them from oxidative stress and can be responsible for reducing the protein glycation. This cytokinin has been found to contribute to the prevention of skin aging [78, 90]. (…) According to the literature, kinetin has little or no photoprotection effect compared to other compounds and, therefore, should not be used in sunscreens [92]”.

 

Line 375. The following paragraph was added: “Peptides can be divided into three groups: signal peptides, carrier peptides and neurotransmitter-inhibiting peptides [48]. (…) These peptides penetrate skin and relax muscles, causing the reduction and softening of wrinkles and fine lines [48]”.

 

Author Response File: Author Response.docx

Reviewer 4 Report

It as an interesting manuscript and interesting commercial modern products are presented.

I think that the paragraph regarding growth factors and cosmetics should be absolutely rewritten. It is presented such as growth factors are permitted as it is to be used as cosmetic ingredients. There is a bit mess regarding cosmetics, wound healing agents, market products in USA, references about wound healing, real growth factors, in vitro produced growth factos, recombinant growth factors, in vitro studies, in vivo studies. What is really permitted to be used in cosmetics in Europe and USA has to be remarked. Finished commercial products and well known cosmetic ingredients are mixed in this manuscript.

A. The reference 44 of the submitted manuscript describes the use of growth factors by the references 14-18

14 Sproul EP, Argraves WS. A cytokine axis regulates elastin formation and degradation. Matrix Biol. 2013;32(2):86–94.

15 Uitto J, Kouba D. Cytokine modulation of extracellular matrix gene expression: relevance to fibrotic skin diseases. J Dermatol Sci. 2000;24(Suppl 1):S60–S69.

16 Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol. 2007;13(22):3056–3062.

17 Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Ther. 2007;20(5):350–359.

18 Schaefer H, Lademann J. The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol. 2001;14(Suppl 1):23–27.

Comments: References 14-18

14. Sproul EP, Argraves WS. A cytokine axis regulates elastin formation and degradation. Matrix Biol. 2013;32(2):86–94. Comment In vitro experiments
15. Uitto J, Kouba D. Cytokine modulation of extracellular matrix gene expression: relevance to fibrotic skin diseases. J Dermatol Sci. 2000;24(Suppl 1):S60–S69. Comment In vitro experiments

"Fibroblasts experiments. Conclusion This summary also provides evidence in support of the notion that transcriptional activation of collagen gene expression is the underlying mechanism leading to development of fibrotic cutaneous lesions, as documented in keloids, a prototypic example of cutaneous fibrosis."

16. Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol. 2007;13(22):3056–3062. Comment Biochemical mechanisms-review

"This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes".

17. Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Ther. 2007;20(5):350–359. Comment Very interesting and well designed old clinical study. The only one reffered to volunteers with clinical signs of photoaging and possible recovery. But in the same paper the potential dangers of the use of growth factors as”cosmeceuticals” are extensively discussed. In vitro produced growth factors.
18. Schaefer H, Lademann J. The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol. 2001;14(Suppl 1):23–27.  Comment It describes only the mechanisms of skin-follicular penetration, in general.

19. . De Buys Roessingh AS, Hohlfeld J, Scaletta C, et al. Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. Cell Transplant. 2006;15(8–9):823–834

Comment It refers to wound healing

B. Reference 28 of the submitted manuscript

Comment  significant, old clinical study. in vitro produced growth factors

C. Reference 33 of the submitted manuscript

Hardwicke J, Schmaljohann D, Boyce D, Thomas D. Epidermal growth factor therapy and wound healing – past, present and future perspectives. Surgeon. 2008;6(3):172–177.

Comment Wound healing agents

 

Market products

Processed skin proteins (PSP®) by Neocutis® (Merz North America, Inc., Raleigh, NC, USA)

TNS® (SkinMedica, Carlsbad, CA, USA), in ωitro produced growth factors

ReGenica® (Histogen Aesthetics, San Diego, CA, USA) (in vitro produced growth factors)

EGF serum (Bioeffect, Kopavogur, Iceland) recombinant EGF

CRS with growth factor (Topix Pharmaceuticals, Amityville, NY, USA) recombinant TGF β1

Author Response

Point 1:  I think that the paragraph regarding growth factors and cosmetics should be absolutely rewritten. It is presented such as growth factors are permitted as it is to be used as cosmetic ingredients. There is a bit mess regarding cosmetics, wound healing agents, market products in USA, references about wound healing, real growth factors, in vitro produced growth factors, recombinant growth factors, in vitro studies, in vivo studies. What is really permitted to be used in cosmetics in Europe and USA has to be remarked. Finished commercial products and well-known cosmetic ingredients are mixed in this manuscript.

A. The reference 44 of the submitted manuscript describes the use of growth factors by the references 14-18

14 Sproul EP, Argraves WS. A cytokine axis regulates elastin formation and degradation. Matrix Biol. 2013;32(2):86–94.

15 Uitto J, Kouba D. Cytokine modulation of extracellular matrix gene expression: relevance to fibrotic skin diseases. J Dermatol Sci. 2000;24(Suppl 1):S60–S69.

16 Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol. 2007;13(22):3056–3062.

17 Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Ther. 2007;20(5):350–359.

18 Schaefer H, Lademann J. The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol. 2001;14(Suppl 1):23–27.

 

Comments: References 14-18

Sproul EP, Argraves WS. A cytokine axis regulates elastin formation and degradation. Matrix Biol. 2013;32(2):86–94. Comment In vitro experiments

Uitto J, Kouba D. Cytokine modulation of extracellular matrix gene expression: relevance to fibrotic skin diseases. J Dermatol Sci. 2000;24(Suppl 1):S60–S69. Comment In vitro experiments

"Fibroblasts experiments. Conclusion This summary also provides evidence in support of the notion that transcriptional activation of collagen gene expression is the underlying mechanism leading to development of fibrotic cutaneous lesions, as documented in keloids, a prototypic example of cutaneous fibrosis."

Verrecchia F, Mauviel A. Transforming growth factor-beta and fibrosis. World J Gastroenterol. 2007;13(22):3056–3062. Comment Biochemical mechanisms-review

"This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes"

Mehta RC, Fitzpatrick RE. Endogenous growth factors as cosmeceuticals. Dermatol Ther. 2007;20(5):350–359. Comment Very interesting and well designed old clinical study. The only one reffered to volunteers with clinical signs of photoaging and possible recovery. But in the same paper the potential dangers of the use of growth factors as “cosmeceuticals” are extensively discussed. In vitro produced growth factors.

Schaefer H, Lademann J. The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol. 2001;14(Suppl 1):23–27.  Comment It describes only the mechanisms of skin-follicular penetration, in general.

De Buys Roessingh AS, Hohlfeld J, Scaletta C, et al. Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. Cell Transplant. 2006;15(8–9):823–834

Comment It refers to wound healiing

B. Reference 28 of the submitted manuscript

Comment  significant, old clinical study. in vitro produced growth factors

C. Reference 33 of the submitted manuscript

Hardwicke J, Schmaljohann D, Boyce D, Thomas D. Epidermal growth factor therapy and wound healing – past, present and future perspectives. Surgeon. 2008;6(3):172–177.

Comment Wound healing agents

 

Response 1: Thank you for your comment. The section about Growth Factors was rewritten.

We apologize, but honestly, we don't understand some of the comments you made about references 14-18, 28, and 33. We think there must have been a mistake, because in our manuscript, these references have nothing to do with growth factors. We would appreciate a clarification about these comments.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

In my opinion the manuscript has been significantly
improved and now warrants publication in Cosmetics.

Author Response

Point 1: In my opinion the manuscript has been significantly improved and now warrants publication in Cosmetics

 

Response 1: We are very grateful for your comments.

Reviewer 2 Report

I agree there are various potentials in biotechnology, this is a kind of production method, it can be used for many chemical ingredients. However, it doesn't mean you can use it all in cosmetics. As I said before, you confused the cosmetics and other medical actions. Cosmetics are distinctly different from aesthetic medicine and cosmetic surgery treatments. Cosmetics are widely used by the general public and have no risks. Of course, hormones and cells cannot be used. Therefore you should separate ingredients for normal and commercial cosmetics, and aesthetic medicines used by medical doctors for a special patient. If you stick to the field of cosmetics, you should exclude cells and hormones. or change the title into Biotechnology applied to cosmetics and aesthetic medicines.

Author Response

Point 1: I agree there are various potentials in biotechnology, this is a kind of production method, it can be used for many chemical ingredients. However, it doesn't mean you can use it all in cosmetics. As I said before, you confused the cosmetics and other medical actions. Cosmetics are distinctly different from aesthetic medicine and cosmetic surgery treatments. Cosmetics are widely used by the general public and have no risks. Of course, hormones and cells cannot be used. Therefore you should separate ingredients for normal and commercial cosmetics, and aesthetic medicines used by medical doctors for a special patient. If you stick to the field of cosmetics, you should exclude cells and hormones. or change the title into Biotechnology applied to cosmetics and aesthetic medicines.

 

Response 1: We appreciate your suggestion and completely agree to change the title of the manuscript to “Biotechnology applied to cosmetics and aesthetic medicines”.

Reviewer 3 Report

These revisions were extremely helpful to the quality of the paper.

Author Response

Point 1: These revisions were extremely helpful to the quality of the paper.

 

Response 1: We are very grateful for your comments.

Reviewer 4 Report

Response to the authors

You have to read what I  have written in my comments. 

In details:

lines 155- 156 of your first submission:routinely used in all high-quality cosmetics [12]. "Here in, topical growth factors have gained 155 increasing interest as skin rejuvenation assets [44]." 

line 390 (ref 44) of your first submission:   "Fabi, S.; Sundaram, H. The potential of topical and injectable growth factors and cytokines for skin  rejuvenation. Facial Plast. Surg. 2014, 30, 157 - 171. This article sites other articles (14-18) that do not match very well with the paragraph for growth factors of your manuscript. 

 

Finally in the revision of your manuscript, the paragraph about peptides is well written. 

 

Author Response

Point 1: You have to read what I have written in my comments.

In details

lines 155- 156 of your first submission: routinely used in all high-quality cosmetics [12]. "Here in, topical growth factors have gained 155 increasing interest as skin rejuvenation assets [44]."

line 390 (ref 44) of your first submission: "Fabi, S.; Sundaram, H. The potential of topical and injectable growth factors and cytokines for skin  rejuvenation. Facial Plast. Surg. 2014, 30, 157 - 171. This article sites other articles (14-18) that do not match very well with the paragraph for growth factors of your manuscript.

Finally in the revision of your manuscript, the paragraph about peptides is well written.

 

Response 1: Thank you for your comment. The section relating to growth factors has been rewritten and the paragraph concerning the citation of reference [44], now reference [50], was completely replaced in the last submitted version of the manuscript