The Role of Ion-Doped Hydroxyapatite in Drug Delivery, Tissue Engineering, Wound Healing, Implants, and Imaging
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe explanations of the Fig. 1 should be posted on the same page with picture it self not on the next page. The editor of the text knows exactly how to do this.
Author Response
Reviewer 1:
the explanations of the Fig. 1 should be posted on the same page with picture it self not on the next page. The editor of the text knows exactly how to do this.
Response: Thanks for your comment. done.
Reviewer 2 Report
Comments and Suggestions for AuthorsThis review paper is about the ion doping of hydroxyapatite (HA) to improve its characteristics and enhance its effectiveness in biomedical applications. The biomedical applications highlighted in this article are drug delivery systems, tissue engineering, implant coating, wound healing, and multimodal imaging. Depending on the dopant, the HA can have distinct mechanical, physicochemical, and biological properties. The dopants include zinc, copper, silver, nickel, magnesium, etc.
The aim of this article is to highlight the roles of ion-doped HA (iHA) in biomedical applications, including drug delivery, wound dressing, and tissue engineering. The discussed topics are introduction, Ion-doped hydroxyapatite (iHA), synthesis of iHA, iHA for drug delivery systems, iHA for tissue engineering, iHA for Wound healing, iHA for Coating Implants, iHA for multimodal Imaging and conclusion and future perspectives. In every topic, the procedure, aim and results of related papers and studies are explained and discussed.
1) The reference for all figures is reported.
2) Figures should be in scalable vector graphics (SVG) format.
3) The applications of iHA discussed in this article should be better summarized in the final section. This will give readers an overview of the properties of this material class and better illustrate the connection between the suggestions made and the studies referenced.
4) It is recommended to use the following references. Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System. A novel in situ gelling probiotic microparticle formulation as a healing dressing for infectious burn wounds using QbD principles.
5) Reducing the number of illustrations in each figure would simplify the description and decrease the complexity of the figures.
No more suggestions.
Author Response
Reviewer 2:
1) The reference for all figures is reported.
Response: Thanks for your positive comment.
2) Figures should be in scalable vector graphics (SVG) format.
Response: Thanks for your comment. done.
3) The applications of iHA discussed in this article should be better summarized in the final section. This will give readers an overview of the properties of this material class and better illustrate the connection between the suggestions made and the studies referenced.
Response: Thanks for your comment. We completely changed the last section. done.
4) It is recommended to use the following references. Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System. A novel in situ gelling probiotic microparticle formulation as a healing dressing for infectious burn wounds using QbD principles.
Response: Thanks for the recommended references. [2], [3]. done.
5) Reducing the number of illustrations in each figure would simplify the description and decrease the complexity of the figures.
Response: Thanks for your comment. Actually, the number of figures were more than what it is. We had to remove some of them. The remained images were selected carefully to support or text because in some cases images are mandatory for readers to understand the issue. SO, we will be thankful if you accept our images in their current condition.
Reviewer 3 Report
Comments and Suggestions for AuthorsThis review manuscript deals with an scientifically challenging topic, having a sound theoretical background, a robust analytical and methodological review, and the creative discussion on findings. All research parts have been fully developed, offering a broad and systematic convey of all multiparametric aspects of the emerging issues on “Ion-Doped Hydroxyapatite in Drug Delivery, Tissue Engineering, Wound Healing, Implants, and Imaging”. In this context the manuscript sustains novel features and it is already in a publishable statues, thus, I recommend it to be accepted for publication at the Chemistry journal as is.
Author Response
Reviewer 3:
this review manuscript deals with an scientifically challenging topic, having a sound theoretical background, a robust analytical and methodological review, and the creative discussion on findings. All research parts have been fully developed, offering a broad and systematic convey of all multiparametric aspects of the emerging issues on “Ion-Doped Hydroxyapatite in Drug Delivery, Tissue Engineering, Wound Healing, Implants, and Imaging”. In this context the manuscript sustains novel features and it is already in a publishable statues, thus, I recommend it to be accepted for publication at the Chemistry journal as is.
Response: Thanks for your kind comments. It our pleasure.
Reviewer 4 Report
Comments and Suggestions for Authors
The submitted manuscript is a low-medium quality review, that is not systematic, on the doped HA structures and their applications. To be honest, I don’t like this work much. First 9 pages can be summarized into one sentence “doped HA exists and can be possibly used”. Then, the subsequent paragraphs look like rephrased abstracts from the randomly chosen experimental works. According to Scopus, there are over 50 review papers on the doped HA published in 2020’s, some of them even in the MDPI journals like this one: 10.3390/bioengineering10121367 . The one submitted by the Authors simply brings nothing new and is too shallow. Instead of focusing on multiple aspects such as those five mentioned in the title, the Authors should focus on one of them and analyze all of the available literature, in a systematic way, following the PRISMA guidelines. Also, the language must be polished significantly.
Line 20, it should be „doped HA”
Line 27, it should be “zinc”
Line 29, it should be “strontium”, “cobalt”, “nickle”
Lines 30 and 32, please write the name of elements starting with small, not capital letter
Lines 26-27, “More importantly, some ions have the potential to prepare HA for wound healing” – this sentence makes no sense
Lines 63-64, this sentence is grammatically incorrect
Line 118, not only calcium ions…
Line 134, here, the crystal structure of HA should be described and presented
Line 138, the Authors should decide whether they use IDHA or iHA, as suggested in the table presenting abbreviations
Line 147, not only calcium, phosphate ions can be substituted as well
Line 189, but this is the reaction of the formation of non-doped HA
Figure 1, first of all, this method is just an example of how the doped HA can be obtained, more methods should be presented. Second, what those bacteria are doing there?
Lines 213, 221, etc. – the authors should use superscripts and subscripts for ions
Comments on the Quality of English Language
There are multiple grammar mistakes.
Author Response
Reviewer 4:
The submitted manuscript is a low-medium quality review, that is not systematic, on the doped HA structures and their applications. To be honest, I don’t like this work much. First 9 pages can be summarized into one sentence “doped HA exists and can be possibly used”. Then, the subsequent paragraphs look like rephrased abstracts from the randomly chosen experimental works. According to Scopus, there are over 50 review papers on the doped HA published in 2020’s, some of them even in the MDPI journals like this one: 10.3390/bioengineering10121367 . The one submitted by the Authors simply brings nothing new and is too shallow. Instead of focusing on multiple aspects such as those five mentioned in the title, the Authors should focus on one of them and analyze all of the available literature, in a systematic way, following the PRISMA guidelines. Also, the language must be polished significantly.
Response: Thanks for taking time and reading our paper. We highly appreciate your comments. Considering this comment, We would like to say that our paper has significant differences compared to the previous one. The paper that you mentioned is just about bone tissue engineering while we studied the role iHA not only in tissue engineering but also in wound healing, drug delivery, and also multimodal imaging (no review has been made for multimodal imaging with a focus on iHA). Our paper is a great recommendation for student who would like to work on iHA for biomedical applications. Besides we explained the different technique to synthesize iHA which the one that you recommended did not.
So, We will be thankful if you consider our paper with the mentioned points and we hope it is satisfactory.
Considering your final recommendation, based on this review paper, which has been a part of our literature review, we decided to direct our experimental research towards using iHA for multimodal imaging. So, we will do more literature review and we will perform a systematic review simultaneously. We guarantee that we will finish the systematic review soon.
Line 20, it should be „doped HA”
Response: Thanks for your comment. done.
Line 27, it should be “zinc”
Response: Thanks for your comment. done.
Line 29, it should be “strontium”, “cobalt”, “nickle”
Response: Thanks for your comment. done.
Lines 30 and 32, please write the name of elements starting with small, not capital letter
Response: Thanks for your comment. done.
Lines 26-27, “More importantly, some ions have the potential to prepare HA for wound healing” – this sentence makes no sense
Response: Thanks for your comment. the sentence was rewritten.
Lines 63-64, this sentence is grammatically incorrect
Response: Thanks for your comment. the sentence was rewritten.
Line 118, not only calcium ions…
Response: Thanks for your comment. the sentence was rewritten.
Line 134, here, the crystal structure of HA should be described and presented
Response: Thanks for your comment. done.
Line 138, the Authors should decide whether they use IDHA or iHA, as suggested in the table presenting abbreviations
Response: Thanks for your comment. iHA has been selected. done.
Line 147, not only calcium, phosphate ions can be substituted as well
Response: Thanks for your comment. done.
Line 189, but this is the reaction of the formation of non-doped HA
Response: Thanks for your comment. yes that is right. In the previous line of the reaction (187-188), we mentioned that this is how HA is synthesized. In the rest we discussed iHA synthesis.
Figure 1, first of all, this method is just an example of how the doped HA can be obtained, more methods should be presented. Second, what those bacteria are doing there?
Response: Thanks for your comment. if we understood your comment correctly, considering the first point, actually we would like to use more images but providing many images need more spaces considering the limitations by journal. Also, this section is just a small section and one image seems more appropriate. Besides, A and B are two different methods to obtain iHA.
About the bacteria, it was a wise comments and we appreciate it. We removed them. Thanks for that.
Lines 213, 221, etc. – the authors should use superscripts and subscripts for ions
Response: Thanks for your comment. done.
Round 2
Reviewer 4 Report
Comments and Suggestions for AuthorsThe Authors have done the suggested corrections. While I still think that the aspect of novelty of this review is very limited, from the technical point of view it is acceptable.
