A Brief Review of Current Trends in the Additive Manufacturing of Orthopedic Implants with Thermal Plasma-Sprayed Coatings to Improve the Implant Surface Biocompatibility

Round 1

Reviewer 1 Report

• The extended version of the OCED abbreviation should be given. Similarly, other abbreviations should be checked throughout the manuscript.

• There is no need to use the extended version again after using the abbreviation. It should be checked throughout the manuscript.

• “ This review article focuses on the additive manufacturing of orthopedic implants and thermal plasma spraying of biocompatible coatings, discussing their challenges and benefits based on the authors' experience with selective laser melting and microplasma spraying of metal-ceramic coatings…this review considers a complex the main challenges and trends in the production of patient-specific orthopedic implants with improved antibacterial properties and surface biocompatibility….”. It may be considered to revise the study title in a way that is suitable for these sentences and in accordance with the sub-titles.

• A table can be added to the "2 Additive manufacturing of orthopedic implants: advantages and challenges" section in accordance with the title of the section.

• The heading “3 Requirements and materials for metal and ceramic coatings of orthopedic implants” can be divided into sub-headings as “3.1”, “3.2”.

• Layers can be shown by marking on Figure 2. a and b are written for the figure in two places.

• A table with examples of requirements and materials can be added to section 3.

• Numerical values can be added to expressions such as “The porosity of the implant coating also affects.. The surface roughness of the implant also affects…” by referring to the literature.

• The 4th heading should consist of a single statement, or the two statements separated by a period should be given as two separate headings.

• Figure 3 and Figure 4 can be given in high resolution.-scales and texts should be clear and visible-

• “6. Future perspectives” section should be added.

• References from recent years (especially 2023 and 2022) can be increased.

• Care should be taken not to use the exact same expressions used in other studies in the literature: https://doi.org/10.2478/msp-2022-0043, https://doi.org/10.2478/adms-2021-0013

Author Response

We have carefully considered all of the reviewers’ valuable comments and suggestions regarding our manuscript. We greatly appreciate the time and effort you have dedicated to reviewing our manuscript “Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility”. We have made significant revisions and addressed each of the concerns in the revised version of the manuscript. Point-by-point responses to the referees’ comments are given below.

• The extended version of the OCED abbreviation should be given. Similarly, other abbreviations should be checked throughout the manuscript.

OECD abbreviation was given (lines 59-60, page ), and other abbreviations were checked throughout the text were fixed (EFFORT – lines 55-56, page )

• There is no need to use the extended version again after using the abbreviation. It should be checked throughout the manuscript.

Extended versions were corrected (highlighted throughout the text in yellow)

• “ This review article focuses on the additive manufacturing of orthopedic implants and thermal plasma spraying of biocompatible coatings, discussing their challenges and benefits based on the authors' experience with selective laser melting and microplasma spraying of metal-ceramic coatings…this review considers a complex the main challenges and trends in the production of patient-specific orthopedic implants with improved antibacterial properties and surface biocompatibility….”. It may be considered to revise the study title in a way that is suitable for these sentences and in accordance with the sub-titles.

The title of the paper was revised according to the focus of the article and subtitles and changed to “A brief review of current trends in the additive manufacturing of orthopedic implants with thermal plasma-sprayed coatings to improve the implant surface biocompatibility”.

• A table can be added to the "2 Additive manufacturing of orthopedic implants: advantages and challenges" section in accordance with the title of the section.

Table “The main challenges and advantages of AM of orthopedic implants” was added in section 2 (line 247, page 6)

• The heading “3 Requirements and materials for metal and ceramic coatings of orthopedic implants” can be divided into sub-headings as “3.1”, “3.2”.

The subheadings for section 3 were added as follows – 3.1 Implant Surface Requirements, 3.2 Requirements for in vitro testing, 3.3 Porosity, 3.4 Modulus of elasticity, 3.5 Surface Roughness, 3.6 Materials.

• Layers can be shown by marking on Figure 2. a and b are written for the figure in two places.

Since we are using figures from the published works, we do not have the right to modify them, but we have provided a good-resolution SEM image showing the thickness of the different layers of the multilayer coating.

• A table with examples of requirements and materials can be added to section 3.

Table 2 “Effect of pore size on implant engraftment” and Figure 1 – “Requirements and materials for metal and ceramic coatings of orthopedic implants to obtain a coating with enhanced biocompatibility” were added to section 3 (lines 379-380 page 9 and line 535 page 13)

• Numerical values can be added to expressions such as “The porosity of the implant coating also affects.. The surface roughness of the implant also affects…” by referring to the literature.

Numerical values were added and presented with literature references in Table 2 “Effect of pore size on implant engraftment” (lines 379-380 page 9). Surface roughness values were mentioned by referring to the literature (lines 422,-423, 426, 433,  450-452 on page 10).

• The 4th heading should consist of a single statement, or the two statements separated by a period should be given as two separate headings.

Heading of the section 4 was changed to a single statement “Thermal plasma spraying of metal-ceramic coatings” (line 549, page 13)

• Figure 3 and Figure 4 can be given in high resolution.-scales and texts should be clear and visible-

The quality of the figures has been improved; original digital images have been used. Figure 3 and 4 will be provided in a separate file to increase the high-resolution quality so the text will be clear and visible.

• “6. Future perspectives” section should be added.

Section 5 “Future perspectives” was added (lines 811-843, page 20).

• References from recent years (especially 2023 and 2022) can be increased.

 17 new references (of which 4 for 2023, 10 for 2022 and 3 for 2021) have been incorporated into the manuscript (highlighted in yellow throughout the manuscript):

1. Yi-neng ZHANG, Hai-lin YANG, Akram Nasser JUAIM, Xiao-na CHEN, Chang LU, Ling ZOU, Yin-zhou WANG, Xiong-wen ZHOU, Biocompatibility and osteogenic activity of Zr−30Ta and Zr−25Ta−5Ti sintered alloys for dental and orthopedic implants, Transactions of Nonferrous Metals Society of China, Volume 33, Issue 3, 2023, Pages 851-864, https://doi.org/10.1016/S1003-6326(23)66151-5
2. Naouel Hezil, Linda Aissani, Mamoun Fellah, Mohamed Abdul Samad, Aleksei Obrosov, Chekalkin Timofei, Ekaterina Marchenko. Structural, and tribological properties of nanostructured α + β type titanium alloys for total hip. Journal of Materials Research and Technology, Volume 19, 2022, Pages 3568-3578. https://doi.org/10.1016/j.jmrt.2022.06.042
3. Han J, Li Z, Sun Y, Cheng F, Zhu L, Zhang Y, Zhang Z, Wu J, Wang J. Surface Roughness and Biocompatibility of Polycaprolactone Bone Scaffolds: An Energy-Density-Guided Parameter Optimization for Selective Laser Sintering. Front Bioeng Biotechnol. 2022 Jul 11;10:888267. doi: 10.3389/fbioe.2022.888267. PMID: 35898639; PMCID: PMC9309791.
4. Zhang, Y., Sun, N., Zhu, M., Qiu, Q., Zhao, P., Zheng, C., et al. (2022). The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis. Biomater. Adv. 133, 112651. doi:10.1016/j.msec.2022.112651
5. Rui Wang, Shilei Ni, Li Ma and Meihua Li Porous construction and surface modification of titanium-based materials for osteogenesis: A review Front. Bioeng. Biotechnol., 25 August 2022 Biomaterials Volume 10 - 2022 | https://doi.org/10.3389/fbioe.2022.973297
6. Lei Huang, Xizhang Chen, Sergey Konovalov,  Chuanchu Su, Pengfei Fan,  Yanhu Wang,  Pan Xiaoming, Irina Panchenko A Review of Challenges for Wire and Arc Additive Manufacturing (WAAM) Received: 25 July 2022 / Accepted: 7 November 2022 Trans Indian Inst Met https://doi.org/10.1007/s12666-022-02823-y
7. Linda Aissani, Ahlam Belgroune, Abdenour Saoudi, Abdelhamid Hmima, Mamoun Fellah, Aleksei Obrosov, Akram Alhussein Tribo-mechanical performance and antibacterial activity in (Cu, Zr)-alloyed Ti(Al)N coatings synthesized by reactive magnetron sputtering J Mater Sci (2022) 57:19612–19630 https://doi.org/10.1007/s10853-022-07804-6
8. Naouel Hezil, Linda Aissani, Mamoun Fellah, Mohamed Abdul Samad, Aleksei Obrosov, Chekalkin Timofei, Ekaterina Marchenko. Structural, and tribological properties of nanostructured α + β type titanium alloys for total hip. Journal of Materials Research and Technology, Volume 19, 2022, Pages 3568-3578. https://doi.org/10.1016/j.jmrt.2022.06.042
9. Wang, C., Xu, D., Lin, L., Li, S., Hou, W., He, Y., et al. (2021). Large-pore-size Ti6Al4V scaffolds with different pore structures for vascularized bone regeneration. Mater. Sci. Eng. C 131, 112499. doi:10.1016/j.msec.2021.112499
10. Gao, B.; Zhao, H.; Peng, L.; Sun, Z. A Review of Research Progress in Selective Laser Melting (SLM). Micromachines 2023, 14, 57. https://doi.org/10.3390/mi14010057
11. Saunders, J.; Elbestawi, M.; Fang, Q. Ultrafast Laser Additive Manufacturing: A Review. J. Manuf. Mater. Process. 2023, 7, 89. https://doi.org/10.3390/jmmp7030089
12. Nandhakumar R., Venkatesan K. A process parameters review on selective laser melting-based additive manufacturing of single and multi-material: Microstructure, physical properties, tribological, and surface roughness. Materials Today Communications, Volume 35, 2023, https://doi.org/10.1016/j.mtcomm.2023.105538
13. Srivastava, Manu & Rathee, Sandeep & Patel, Vivek & Kumar, Atul & Koppad, Praveennath. (2022). A review of various materials for additive manufacturing: Recent trends and processing issues. Journal of Materials Research and Technology. 21. 10.1016/j.jmrt.2022.10.015
14. Zhai, Xiaoya & Jin, Liuchao & Jiang, Jingchao. (2022). A survey of additive manufacturing reviews. 10.18063/msam.v1i4.21
15. Stich, T.; Alagboso, F.; Křenek, T.; Kovářík, T.; Alt, V.; Docheva, D. Implant-bone-interface: Reviewing the impact of titanium surface modifications on osteogenic processes in vitro and in vivo. Bioengineering & translational medicine 2022, 7, e10239, doi:10.1002/btm2.10239
16. Babak Jahani, Xinnan Wang. The Effects of Surface Roughness on the Functionality of Ti13Nb13Zr Orthopedic Implants. Biomed J Sci & Tech Res 38(1)- 2021. BJSTR. MS.ID.006104
17. Eric A. Lewallen, William H. Trousdale, Roman Thaler, Jie J. Yao, Wei Xu, Janet M. Denbeigh, Asha Nair, Jean-Pierre Kocher, Amel Dudakovic, Daniel J. Berry, Robert C. Co-hen, Matthew P. Abdel, David G. Lewallen, and Andre J. van Wijnen. Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchy-mal Stromal Cells. Tissue Engineering Part A.Dec 2021.1503-1516.http://doi.org/10.1089/ten.tea.2020.0369

• Care should be taken not to use the exact same expressions used in other studies in the literature: https://doi.org/10.2478/msp-2022-0043, https://doi.org/10.2478/adms-2021-0013

We would like to sincerely apologize for this oversight and any potential confusion it may have caused.

As researchers, it is our responsibility to maintain the highest standards of academic integrity and originality in our work. We understand that reusing exact expressions from our own previous studies without proper citation or acknowledgment is not acceptable, as it can give the impression of self-plagiarism or lack of novelty. We deeply regret this mistake and assure you that it was not intentional. We recognize the importance of providing fresh perspectives and innovative insights in our research, and we fully acknowledge the need to avoid repetition of content, particularly within our own body of work.

Actions were taken to paraphrase subsection 3.3 (lines 347-354)

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript, which is a review dedicated to "coatings for orthopaedic implants", is interesting but too scattered to read. The presentation of the results needs to be reorganised by adding tables and other figures because it is difficult to read.

Author Response

Thank you for your valuable feedback on our manuscript titled " Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility." We appreciate your time and effort in thoroughly reviewing our work. We acknowledge the concern you raised regarding the readability and organization of the manuscript.  

To enhance the clarity and organization of the manuscript, we implemented the following improvements:

• the title of the manuscript was revised according to the focus of the article and changed to “A brief review of current trends in the additive manufacturing of orthopedic implants with thermal plasma-sprayed coatings to improve the implant surface biocompatibility”;
• the subheadings for section 3 were added as follows – 3.1 Implant Surface Requirements, 3.2 Requirements for in vitro testing, 3.3 Porosity, 3.4 Modulus of elasticity, 3.5 Surface Roughness, 3.6 Materials;
• table “The main challenges and advantages of AM of orthopedic implants”(line 247, page 6) was added to section 2;
• table “Effect of pore size on implant engraftment”(lines 379-380 page 9) was added in section 3;
• figure “Requirements and materials for metal and ceramic coatings of orthopedic implants to obtain a coating with enhanced biocompatibility”(line 535) was incorporated on page 13.

We also paid close attention to the overall readability of the manuscript, including sentence structure and paragraph transitions.

Author Response File: Author Response.docx

Reviewer 3 Report

The present manuscript titled "Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility" reviews different types of coatings for orthopaedic implants. The review is extensive but poorly organized. The specific comments are as follows-

1. The authors start with introduction, jump to 3D printing which and then to requirements for coating and then a specific coating method. There is no flow in the manuscript.

2. The authors need to make sections and subsections in the manuscript according to the methods they are discussing to develop a flow. This will make the review comprehensible for the readers, which it is not at the moment. 

3. The conclusion is too long and needs to be shortened.

Author Response

We have carefully considered all of the reviewers’ valuable comments and suggestions regarding our manuscript. We greatly appreciate the time and effort they have dedicated to reviewing our manuscript “Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility”. We have made significant revisions and addressed each of the concerns in the revised version of the manuscript. Point-by-point responses to the referees’ comments are attached below.

The present manuscript titled "Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility" reviews different types of coatings for orthopaedic implants. The review is extensive but poorly organized. The specific comments are as follows-

1. The authors start with introduction, jump to 3D printing which and then to requirements for coating and then a specific coating method. There is no flow in the manuscript.

                   We carefully restructured the presentation of our results to ensure a more coherent flow of information We understand the importance of providing a clear and logical framework for readers to follow, and we made sure that the content is appropriately organized. The coherence of the manuscript has been improved to allow a better flow, the conclusions have been shortened, making the consistency with the objectives of the review clearer.

2. The authors need to make sections and subsections in the manuscript according to the methods they are discussing to develop a flow. This will make the review comprehensible for the readers, which it is not at the moment. 

The subheadings for section 3 were added as follows – 3.1 Implant Surface Requirements, 3.2 Requirements for in vitro testing, 3.3 Porosity, 3.4 Modulus of elasticity, 3.5 Surface Roughness, 3.6 Materials.

The title of the manuscript was revised according to the focus of the article and changed to “A brief review of current trends in the additive manufacturing of orthopedic implants with thermal plasma-sprayed coatings to improve the implant surface biocompatibility”.

To improve the coherence and readability of the manuscript, generalizing figures and tables were added in the appropriate subsections:

• -table “The main challenges and advantages of AM of orthopedic implants”( line 247, page 6) was added to section 2;
• -table “Effect of pore size on implant engraftment”( lines 379-380 page 9) was added in section 3;
• -figure “Requirements and materials for metal and ceramic coatings of orthopedic implants to obtain a coating with enhanced biocompatibility”(line 535) was incorporated on page 13.

3. The conclusion is too long and needs to be shortened.

We understand your concern regarding the length of the conclusion section, and we agree that it can be condensed to ensure conciseness and clarity. To address this issue, we shortened the conclusion to 230 words, by highlighting the most significant findings and key points from the manuscript in a concise manner.  Our intention was to strike a balance between providing a comprehensive summary of our research and ensuring the conclusion remains concise and accessible. We appreciate your suggestion to improve the overall readability of the manuscript.

Author Response File: Author Response.docx

Reviewer 4 Report

The author has carried out a very comprehensive review of the process but it is required to incorporate the suggestions/comment in their manuscript for better understanding to the researchers.

1. The author should add more recent research articles in this field which are already published in 2023.

2. The research gap followed by the objective should be elaborate.

3. The author should add a table that comprised all the necessary information for easy understanding of researchers in the additive manufacturing section and thermal spray coating section.

4. Future scope should be added before conclusions.

Author Response

We have carefully considered all of the reviewers’ valuable comments and suggestions regarding our manuscript. We greatly appreciate the time and effort they have dedicated to reviewing our manuscript “Coatings for orthopedic metal implants: a brief review of modern trends in the manufacture of implants with improved surface biocompatibility”. We have made significant revisions and addressed each of the concerns in the revised version of the manuscript. Point-by-point responses to the referees’ comments are given below:

The author has carried out a very comprehensive review of the process but it is required to incorporate the suggestions/comment in their manuscript for better understanding to the researchers.

1. The author should add more recent research articles in this field which are already published in 2023.

 17 new references of recent research articles (of which 4 for 2023, 10 for 2022, and 3 for 2021) have been added to the manuscript (highlighted in yellow throughout the manuscript):

1. Yi-neng ZHANG, Hai-lin YANG, Akram Nasser JUAIM, Xiao-na CHEN, Chang LU, Ling ZOU, Yin-zhou WANG, Xiong-wen ZHOU, Biocompatibility and osteogenic activity of Zr−30Ta and Zr−25Ta−5Ti sintered alloys for dental and orthopedic implants, Transactions of Nonferrous Metals Society of China, Volume 33, Issue 3, 2023, Pages 851-864, https://doi.org/10.1016/S1003-6326(23)66151-5
2. Naouel Hezil, Linda Aissani, Mamoun Fellah, Mohamed Abdul Samad, Aleksei Obrosov, Chekalkin Timofei, Ekaterina Marchenko. Structural, and tribological properties of nanostructured α + β type titanium alloys for total hip. Journal of Materials Research and Technology, Volume 19, 2022, Pages 3568-3578. https://doi.org/10.1016/j.jmrt.2022.06.042
3. Han J, Li Z, Sun Y, Cheng F, Zhu L, Zhang Y, Zhang Z, Wu J, Wang J. Surface Roughness and Biocompatibility of Polycaprolactone Bone Scaffolds: An Energy-Density-Guided Parameter Optimization for Selective Laser Sintering. Front Bioeng Biotechnol. 2022 Jul 11;10:888267. doi: 10.3389/fbioe.2022.888267. PMID: 35898639; PMCID: PMC9309791.
4. Zhang, Y., Sun, N., Zhu, M., Qiu, Q., Zhao, P., Zheng, C., et al. (2022). The contribution of pore size and porosity of 3D printed porous titanium scaffolds to osteogenesis. Biomater. Adv. 133, 112651. doi:10.1016/j.msec.2022.112651
5. Rui Wang, Shilei Ni, Li Ma and Meihua Li Porous construction and surface modification of titanium-based materials for osteogenesis: A review Front. Bioeng. Biotechnol., 25 August 2022 Biomaterials Volume 10 - 2022 | https://doi.org/10.3389/fbioe.2022.973297
6. Lei Huang, Xizhang Chen, Sergey Konovalov,  Chuanchu Su, Pengfei Fan,  Yanhu Wang,  Pan Xiaoming, Irina Panchenko A Review of Challenges for Wire and Arc Additive Manufacturing (WAAM) Received: 25 July 2022 / Accepted: 7 November 2022 Trans Indian Inst Met https://doi.org/10.1007/s12666-022-02823-y
7. Linda Aissani, Ahlam Belgroune, Abdenour Saoudi, Abdelhamid Hmima, Mamoun Fellah, Aleksei Obrosov, Akram Alhussein Tribo-mechanical performance and antibacterial activity in (Cu, Zr)-alloyed Ti(Al)N coatings synthesized by reactive magnetron sputtering J Mater Sci (2022) 57:19612–19630 https://doi.org/10.1007/s10853-022-07804-6
8. Naouel Hezil, Linda Aissani, Mamoun Fellah, Mohamed Abdul Samad, Aleksei Obrosov, Chekalkin Timofei, Ekaterina Marchenko. Structural, and tribological properties of nanostructured α + β type titanium alloys for total hip. Journal of Materials Research and Technology, Volume 19, 2022, Pages 3568-3578. https://doi.org/10.1016/j.jmrt.2022.06.042
9. Wang, C., Xu, D., Lin, L., Li, S., Hou, W., He, Y., et al. (2021). Large-pore-size Ti6Al4V scaffolds with different pore structures for vascularized bone regeneration. Mater. Sci. Eng. C 131, 112499. doi:10.1016/j.msec.2021.112499
10. Gao, B.; Zhao, H.; Peng, L.; Sun, Z. A Review of Research Progress in Selective Laser Melting (SLM). Micromachines 2023, 14, 57. https://doi.org/10.3390/mi14010057
11. Saunders, J.; Elbestawi, M.; Fang, Q. Ultrafast Laser Additive Manufacturing: A Review. J. Manuf. Mater. Process. 2023, 7, 89. https://doi.org/10.3390/jmmp7030089
12. Nandhakumar R., Venkatesan K. A process parameters review on selective laser melting-based additive manufacturing of single and multi-material: Microstructure, physical properties, tribological, and surface roughness. Materials Today Communications, Volume 35, 2023, https://doi.org/10.1016/j.mtcomm.2023.105538
13. Srivastava, Manu & Rathee, Sandeep & Patel, Vivek & Kumar, Atul & Koppad, Praveennath. (2022). A review of various materials for additive manufacturing: Recent trends and processing issues. Journal of Materials Research and Technology. 21. 10.1016/j.jmrt.2022.10.015
14. Zhai, Xiaoya & Jin, Liuchao & Jiang, Jingchao. (2022). A survey of additive manufacturing reviews. 10.18063/msam.v1i4.21
15. Stich, T.; Alagboso, F.; Křenek, T.; Kovářík, T.; Alt, V.; Docheva, D. Implant-bone-interface: Reviewing the impact of titanium surface modifications on osteogenic processes in vitro and in vivo. Bioengineering & translational medicine 2022, 7, e10239, doi:10.1002/btm2.10239
16. Babak Jahani, Xinnan Wang. The Effects of Surface Roughness on the Functionality of Ti13Nb13Zr Orthopedic Implants. Biomed J Sci & Tech Res 38(1)- 2021. BJSTR. MS.ID.006104
17. Eric A. Lewallen, William H. Trousdale, Roman Thaler, Jie J. Yao, Wei Xu, Janet M. Denbeigh, Asha Nair, Jean-Pierre Kocher, Amel Dudakovic, Daniel J. Berry, Robert C. Co-hen, Matthew P. Abdel, David G. Lewallen, and Andre J. van Wijnen. Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchy-mal Stromal Cells. Tissue Engineering Part A.Dec 2021.1503-1516.http://doi.org/10.1089/ten.tea.2020.0369

2. The research gap followed by the objective should be elaborate.

In order to elaborate on the research gap followed by the objective, we have improved the organization of the manuscript to focus on the research gap mentioned in the Introduction section. The title of the manuscript was revised according to the focus of the article and changed to “A brief review of current trends in the additive manufacturing of orthopedic implants with thermal plasma-sprayed coatings to improve the implant surface biocompatibility”. The subheadings for section 3 were added as follows – 3.1 Implant Surface Requirements, 3.2 Requirements for in vitro testing, 3.3 Porosity, 3.4 Modulus of elasticity, 3.5 Surface Roughness, 3.6 Materials. Each subsection of the manuscript shows different points of view on the problem under discussion, demonstrating the existing research gap, declared before setting the goal of this review. The coherence of the manuscript has been improved to allow a better flow, the conclusions have been shortened, making the consistency with the objectives of the review clearer.

3. The author should add a table that comprised all the necessary information for easy understanding of researchers in the additive manufacturing section and thermal spray coating section.

Tables  “The main challenges and advantages of AM of orthopedic implants” ( line 247, page 6)and   “Effect of pore size on implant engraftment”( lines 379-380 page 9) as well as Figure “Requirements and materials for metal and ceramic coatings of orthopedic implants to obtain a coating with enhanced biocompatibility”(line 535, page 13) were added to the manuscript to improve the understanding of researchers

4. Future scope should be added before conclusions.

Section 5 “Future perspectives” was added to the manuscript (lines 811-843, page 20) before conclusion.

Author Response File: Author Response.docx

Round 2

Reviewer 4 Report

No Comments.