Application of Zr and Ti-Based Bulk Metallic Glasses for Orthopaedic and Dental Device Materials
Round 1
Reviewer 1 Report
This review article deals with the interesting field of bulk metallic glasses as biomaterials. This is a topical biomedical matter and can be of interest to the readership of Metals journal.
This manuscript replicates the contents of a recent review article on the same subject (Li HF, Zheng YF. Recent advances in bulk metallic glasses for biomedical applications. Acta Biomater 2016; 36:1-20), that the authors have not considered in their analysis of the literature. This article must be cited and the authors should highlight the points of novelty of their present work in respect with that previous one.
When dealing with biomaterials for dental implants, which are accessible to microbial contamination, another key issue is related to the adhesiveness of the implant surfaces to oral bacteria: the authors should include a chapter on this point.
Paragraph 5 can be omitted: perhaps some concepts could be transposed to the Introduction.
The English language is sometimes peculiar and there are scattered mistakes, but this issue can be easily addressed with the help of a mother-tongue reviewer.
Author Response
We are grateful for very helpful comments. We have revised the manuscript accordingly. The revised parts are underlined in the manuscript. The response to each comment is summarized in the following.
Point number 1-1.
Reviewer’s comment
This manuscript replicates the contents of a recent review article on the same subject (Li HF, Zheng YF. Recent advances in bulk metallic glasses for biomedical applications. Acta Biomater 2016; 36:1-20), that the authors have not considered in their analysis of the literature. This article must be cited and the authors should highlight the points of novelty of their present work in respect with that previous one.
Our responses
We agree with the reviewer’s comment and added the sentences and the reference below.
Text change
A recent article showed potentials of Ti, Zr, Fe, Mg, Zn, Ca, and Sr-based BMGs in biomedical applications [59]. This article specializes in Zr and Ti-based BMGs, which are non-biodegradable, higher strength, higher elasticity, higher failure resistance, and lower Young’s modulus compared with crystalline alloys. This article also refers to dental applications including adhesiveness of material surfaces to oral bacteria.
Li, H.F., Zheng, Y.F. Recent advances in bulk metallic glasses for biomedical applications. Acta Biomater. 2016, 36, 1-20.
Point number 1-2.
Reviewer’s comment
When dealing with biomaterials for dental implants, which are accessible to microbial contamination, another key issue is related to the adhesiveness of the implant surfaces to oral bacteria: the authors should include a chapter on this point.
Our responses
We discussed bacterial adherence of the implant surfaces in section 7.
Text change
The following section was added.
7. Biomaterials for dental device materials
Point number 1-3.
Reviewer’s comment
Paragraph 5 can be omitted: perhaps some concepts could be transposed to the Introduction.
Our responses
We followed all the 4 reviewers’ comments and introduction section was reorganized in the revised manuscript.
Text change
Introduction section was reorganized.
Point number 1-4.
Reviewer’s comment
The English language is sometimes peculiar and there are scattered mistakes, but this issue can be easily addressed with the help of a mother-tongue reviewer.
Our responses
We understand that English is not the authors’ mother tongue and the sentences are not sophisticated. At the same time, we have published more than 40 peer-reviewed original articles without English proofread by native speakers, and we believe that this article meets the requirements of international standards. We can accomplish a proofreading by an English mother tongue in 2 weeks, so please let us know if you evaluate that the article really needs English proofread.
Text change
None.
Reviewer 2 Report
found this review very informative. In my opinion, this MS will become an interesting paper after some minor revisions. I suggest the following modifications and/or improvements:
Since only Zr and Ti-based BMGs are suggested for the targeted applications, the MS would preferably entitled “Application of Ti and Zr-based bulk metallic glasses for orthopaedic and dental device materials”. Paragraphs related to the mechanical properties of the Ti and Zr-based BMGs (l.121 to l.130, l.163 to l.173, and l.201 to l.205) should be summarized in a dedicated sub-section at the beginning of the section 3 (or embedded in the section 2?) before presenting their potential for biomaterial applications. Figure 2 and 3 suffer from the lack of scale bar. A final global proofreading of the MS seems necessary to eliminate: repetitions (l.131-132 with the previous paragraph, l.175 with l.176…), missing words (l.72, l.191…), spelling mistakes (l.72, l.133, l.155, l.224…), indexed number for oxides (l.179-180, l.218…), wrong beginning of sentences (l.92, l.294…). The abovementioned examples are not exhaustive: please, check these defects throughout the MS. Some important contributions such as [1,2] (see below) are not reviewed and could be cited in the MS. Limitations of the targeted applications related to the BMGs components size could be further questioned.[1] Monfared, A., Vali, H., & Faghihi, S. (2013). Biocorrosion and biocompatibility of Zr–Cu–Fe–Al bulk metallic glasses. Surface and Interface Analysis, 45(11-12), 1714-1720.
[2] Liu, L., Qiu, C. L., Huang, C. Y., Yu, Y., Huang, H., & Zhang, S. M. (2009). Biocompatibility of Ni-free Zr-based bulk metallic glasses. Intermetallics, 17(4), 235-240.
Author Response
We are grateful for very helpful comments. We have revised the manuscript accordingly. The revised parts are underlined in the manuscript. The response to each comment is summarized in the following.
Point number 2-1.
Reviewer’s comment
Since only Zr and Ti-based BMGs are suggested for the targeted applications, the MS would preferably entitled “Application of Ti and Zr-based bulk metallic glasses for orthopaedic and dental device materials”.
Our responses
We follow the reviewer’s comment.
Title and text change
“Application of Zr and Ti-based bulk metallic glasses for orthopaedic and dental device materials”
In this review article, in vitro and in vivo studies regarding Zr and Ti-based BMGs applications as biomaterials, especially in orthopaedic and dental device materials, are reviewed.
Point number 2-2.
Reviewer’s comment
Paragraphs related to the mechanical properties of the Ti and Zr-based BMGs (l.121 to l.130, l.163 to l.173, and l.201 to l.205) should be summarized in a dedicated sub-section at the beginning of the section 3 (or embedded in the section 2?) before presenting their potential for biomaterial applications.
Our responses
We followed the reviewer’s comment and mechanical properties were summarized in section 3.
Text change
Mechanical properties of Zr and Ti-based BMGs
Point number 2-3.
Reviewer’s comment
Figure 2 and 3 suffer from the lack of scale bar.
Our responses
We agree with the reviewer’s comment and added the scale bar in Figure 2 and 3.
Text change
Figure 2 and 3 were revised.
Point number 2-4.
Reviewer’s comment
A final global proofreading of the MS seems necessary to eliminate: repetitions (l.131-132 with the previous paragraph, l.175 with l.176…), missing words (l.72, l.191…), spelling mistakes (l.72, l.133, l.155, l.224…), indexed number for oxides (l.179-180, l.218…), wrong beginning of sentences (l.92, l.294…). The abovementioned examples are not exhaustive: please, check these defects throughout the MS.
Our responses
We understand that English is not the authors’ mother tongue and the sentences are not sophisticated and have grammatical mistakes. At the same time, we have published more than 40 peer-reviewed original articles without English proofread by native speakers, and we believe that this article meets the requirements of international standards. We can follow a proofreading by editors or reviewers, so please let us know the better expressions clearly.
Text change
None.
Point number 2-5.
Reviewer’s comment
Some important contributions such as [1,2] (see below) are not reviewed and could be cited in the MS.
[1] Monfared, A., Vali, H., & Faghihi, S. (2013). Biocorrosion and biocompatibility of Zr–Cu–Fe–Al bulk metallic glasses. Surface and Interface Analysis, 45(11-12), 1714-1720.
[2] Liu, L., Qiu, C. L., Huang, C. Y., Yu, Y., Huang, H., & Zhang, S. M. (2009). Biocompatibility of Ni-free Zr-based bulk metallic glasses. Intermetallics, 17(4), 235-240.
Our responses
The papers were cited and reviewed.
Text change
Following sentences and the references were added.
Ni-free Zr-based BMG showed good biocompatibility and biocorrosion in vitro study [49,50]
Liu, L.; Qiu, C.L.; Huang, C.Y.; Yu, Y.; Huang, H.; Zhang, S.M. Biocompatibility of Ni-free Zr-
based bulk metallic glasses. Intermetallics. 2009, 17, 235-240.
Monfared, A.; Vali, H.; Faghihi, S. Biocorrosion and biocompatibility of Zr–Cu–Fe–Al bulk
metallic glasses. Surf. Interface Anal. 2013, 45, 1714-1720.
Point number 2-6.
Reviewer’s comment
Limitations of the targeted applications related to the BMGs components size could be further questioned.
Our responses
We discussed one promising measure to solve the limited components size of BMGs
Text change
Following sentences and the references were added.
One promising measure to solve the limited components size of BMGs is thin film form of Zr and Ti-based BMGs. Metallic glass coating using thin film form onto the substrate of biomedical devices might widen the design and types of implants. Thin film form of Zr and Ti-based BMGs can exhibit a combination of large mechanical properties with good biocompatibility [60] and cytocompatibility [61]. In addition, thin film form of Zr-based BMGs showed size effects on mechanical properties which can be used as coatings for biomedical applications [62,63].
Subramanian, B.; Maruthamuthu, S.; Rajan, S.T. Biocompatibility evaluation of sputtered
zirconium-based thin film metallic glass-coated steels. Int. J. Nanomedicine. 2015, 10, 17-29.
Thanka, R.S.; Bendavid. A; Subramanian, B. Cytocompatibility assessment of Ti-Nb-Zr-Si thin film metallic glasses with enhanced osteoblast differentiation for biomedical applications. Colloids. Surf. B. Biointerfaces. 2019, 173, 109-120.
Ghidelli, M.; Gravier, S.; Blandin, J.J.; Djemia, P.; Mompiou, F.; Abadias, G.; Raskin, J.P.; Pardoen, T. Extrinsic mechanical size effects in thin ZrNi metallic glass films. Acta. Mater. 2015, 90, 232–241. (doi.org/10.1016/j.actamat.2015.02.038)
Ghidelli, M.; Idrissi, H.; Gravier, S.; Blandin, J.J.; Raskin, J.P.; Schryvers, D.; Pardoen, T. Homogeneous flow and size dependent mechanical behavior in highly ductile Zr65Ni35 metallic glass films. Acta. Mater. 2017, 131, 246-259. (doi.org/10.1016/j.actamat.2017.03.072)
Reviewer 3 Report
Manuscript Review for Metals
Manuscript Title: Application of bulk metallic glasses for orthopaedic and dental device materials
Summary: The manuscript is a comprehensive review of bulk metallic glasses that being developed for orthopedic and dental applications. The authors provide adequate background information and then discuss in vitro and in vivo studies aimed at characterizing the potential of different metallic glass alloys for biomedical applications. This a timely report and will be useful to scientists and clinicians working on orthopedic and dental biomaterials. However, the following minor revisions are recommended.
Minor Revisions:
The introduction section can be expanded with appropriate references to describe how BMGs have attractive mechanical properties as well as processability that makes them attractive for biomedical applications. Section 5: Anticorrosion behavior and biocompatibility of BMG..Biocompatibility of BMGs are evaluated by studying the foreign body response to BMGs. This section can be expanded to include the in vivo studies reported in this field (PMIDs: 31058825, 29859902, 25303146). The authors can also include a section on how nanopatterning, surface roughness and chemical composition of BMGs can affect biocompatibility and cell responses. The conclusion section should include some more specifics on what type of in vitro and in vivo studies are recommended for future work in the field.
Author Response
We are grateful for very helpful comments. We have revised the manuscript accordingly. The revised parts are underlined in the manuscript. The response to each comment is summarized in the following.
Point number 3-1.
Reviewer’s comment
The introduction section can be expanded with appropriate references to describe how BMGs have attractive mechanical properties as well as processability that makes them attractive for biomedical applications.
Our responses
We discussed attractive mechanical properties of Zr and Ti-base BMGs in section 3.
Text change
Mechanical properties of Zr and Ti-based BMGs
Point number 3-2.
Reviewer’s comment
Section 5: Anticorrosion behavior and biocompatibility of BMG..Biocompatibility of BMGs are evaluated by studying the foreign body response to BMGs. This section can be expanded to include the in vivo studies reported in this field (PMIDs: 31058825, 29859902, 25303146).
Our responses
We followed the reviewer’s comment.
Text change
The following papers were added to the reference.
Wong, C.C.; Wong, P.C.; Tsai, P.H.; Jang, J.S.; Cheng, C.K.; Chen, H.H.; Chen, C.H.
Biocompatibility and osteogenic capacity of Mg-Zn-Ca bulk metallic glass for rabbit tendon-bone
interference fixation. Int. J. Mol. Sci. 2019, 20, 2191. (PMID 31058825)
Basu, B.; Sabareeswaran, A.; Shenoy, S.J. Biocompatibility property of 100% strontium-substituted SiO2 -Al2 O3 -P2 O5 -CaO-CaF2 glass ceramics over 26 weeks implantation in rabbit model: Histology and micro-Computed Tomography analysis. J. Biomed. Mater. Res. B. Appl. Biomater. 2015, 103, 1168-1179. (PMID 25303146)
Shayan, M.; Padmanabhan, J.; Morris, A.H.; Cheung, B.; Smith, R.; Schroers, J.; Kyriakides, T.R. Nanopatterned bulk metallic glass-based biomaterials modulate macrophage polarization. Acta. Biomater. 2018, 75, 427-438. (PMID 29859902)
Point number 3-3.
Reviewer’s comment
The authors can also include a section on how nanopatterning, surface roughness and chemical composition of BMGs can affect biocompatibility and cell responses.
Our responses
We followed the reviewer’s comment.
Text change
The following sentences were added.
Nanopatterned Pt-based BMGs biomaterials were implanted subcutaneous in mice for 2 weeks and 4 weeks, nanopatterned side facing the dermis. After 2 weeks implantation, ratio of Arg-1 to iNOS expression of macrophages adjacent to 55 nanometer (nm) nanopatterned BMGs (BMG-55) implants increased significantly compared to flat BMGs. Macrophage fusion with fibrous capsule thickness declined after 4 weeks implantation. In addition, the number and size of vessels in tissues surrounding BMG-55 implants increased in 2 weeks implantation and decreased in 4 weeks implantation. The results indicated nanopatterning of BMGs implants is a promising method to modulate macrophage polarization for immune response. Surface roughness and biochemical composition of BMGs might affect biocompatibility, cell responses, and immune response.
Point number 3-4.
Reviewer’s comment
The conclusion section should include some more specifics on what type of in vitro and in vivo studies are recommended for future work in the field.
Our responses
We discussed recommended in vitro and in vivo studies as prospects for the future.
Text change
The following sentences were added.
The other problem of BMGs is the localization of deformation within shear bands reporting a brittle like failure behavior. This limitation is extremely importance especially for in vivo applications, which directly connects with clinical application as orthopaedic and dental device materials. This mechanical property of BMGs could restrain the clinical application. To coat a metallic glass with thin film form of BMGs onto the substrate of biomedical devices might solve this problem. For future work in this field, metallic glass coatings techniques with thin film form of BMGs including in vitro and in vivo studies are recommended.
Reviewer 4 Report
The authors provide a paper dealing with the application of bulk metallic glasses (BMGs) for biomedical applications. The paper can be of interest for Metals, but in its present form it is not acceptable for publication. Here, the reasons:
The authors must discuss in the introduction that not only the BMGs are interesting for biomedical applications but also these materials in thin film form. Specifically, thin film metallic glasses can exhibit a combination of large mechanical properties with good biocompatibility as for the bulk counter parts. The authors must include the following papers doi.org/10.1016/j.actamat.2017.03.072 and doi.org/10.1016/j.actamat.2015.02.038 which report interesting size effects on mechanical properties of this materials which can be used as coatings for biomedical applications. The paper is quite poor of characterizations. There are no SEM images or comments about the evolution of the morphology before and after in-vivo experiments. Some analysis of the failure modes would also be appreciated. A nanoindentation analysis would have also increase the value of the of the paper. The same for more advanced test involving the corrosion behavior of these materials. This part must be improved. One problem of BMGs is the localization of deformation within shear bands reporting a brittle like failure behavior. This part of mechanical properties is not discussed by the authors. I believe that this is of extreme importance especially for in-vivo applications. The authors must comment on the limit of the applications of BMGs and when it would be more convenient to coat a metallic alloy with a thin film metallic glasses.Author Response
We are grateful for very helpful comments. We have revised the manuscript accordingly. The revised parts are underlined in the manuscript. The response to each comment is summarized in the following.
Point number 4-1.
Reviewer’s comment
The authors must discuss in the introduction that not only the BMGs are interesting for biomedical applications but also these materials in thin film form. Specifically, thin film metallic glasses can exhibit a combination of large mechanical properties with good biocompatibility as for the bulk counter parts. The authors must include the following papers doi.org/10.1016/j.actamat.2017.03.072 and doi.org/10.1016/j.actamat.2015.02.038 which report interesting size effects on mechanical properties of this materials which can be used as coatings for biomedical applications.
Our responses
We discuss thin film form of Zr-based BMGs and refer to the papers below in the section of conclusions and future prospects
Text change
Following sentences and the references were added.
One promising measure to solve the limited components size of BMGs is thin film form of Zr and Ti-based BMGs. Metallic glass coating using thin film form onto the substrate of biomedical devices might widen the design and types of implants. Thin film form of Zr and Ti-based BMGs can exhibit a combination of large mechanical properties with good biocompatibility [60] and cytocompatibility [61]. In addition, thin film form of Zr-based BMGs showed size effects on mechanical properties which can be used as coatings for biomedical applications [62,63].
Subramanian, B.; Maruthamuthu, S.; Rajan, S.T. Biocompatibility evaluation of sputtered
zirconium-based thin film metallic glass-coated steels. Int. J. Nanomedicine. 2015, 10, 17-29.
Thanka, R.S.; Bendavid. A; Subramanian, B. Cytocompatibility assessment of Ti-Nb-Zr-Si thin film metallic glasses with enhanced osteoblast differentiation for biomedical applications. Colloids. Surf. B. Biointerfaces. 2019, 173, 109-120.
Ghidelli, M.; Gravier, S.; Blandin, J.J.; Djemia, P.; Mompiou, F.; Abadias, G.; Raskin, J.P.; Pardoen, T. Extrinsic mechanical size effects in thin ZrNi metallic glass films. Acta. Mater. 2015, 90, 232–241. (doi.org/10.1016/j.actamat.2015.02.038)
Ghidelli, M.; Idrissi, H.; Gravier, S.; Blandin, J.J.; Raskin, J.P.; Schryvers, D.; Pardoen, T. Homogeneous flow and size dependent mechanical behavior in highly ductile Zr65Ni35 metallic glass films. Acta. Mater. 2017, 131, 246-259. (doi.org/10.1016/j.actamat.2017.03.072)
Point number 4-2.
Reviewer’s comment
The paper is quite poor of characterizations. There are no SEM images or comments about the evolution of the morphology before and after in-vivo experiments. Some analysis of the failure modes would also be appreciated. A nanoindentation analysis would have also increase the value of the of the paper. The same for more advanced test involving the corrosion behavior of these materials. This part must be improved.
Our responses
The SEM images (Figure 3) with comments before and after in vivo experiment and EDS image (Figure 4) after in vivo experiment, which showed anti-corrosion behavior of Zr-based BMGs were added.
Text change
Figure 3 and Figure 4 were added.
Point number 4-3.
Reviewer’s comment
One problem of BMGs is the localization of deformation within shear bands reporting a brittle like failure behavior. This part of mechanical properties is not discussed by the authors. I believe that this is of extreme importance especially for in-vivo applications. The authors must comment on the limit of the applications of BMGs and when it would be more convenient to coat a metallic alloy with a thin film metallic glasses.
Our responses
We really appreciate the incisive and pertinent comment. The reviewer’s comment is very helpful.
Text change
The following sentences were added.
The other problem of BMGs is the localization of deformation within shear bands reporting a brittle like failure behavior. This limitation is extremely importance especially for in vivo applications, which directly connects with clinical application as orthopaedic and dental device materials. This mechanical property of BMGs could restrain the clinical application. To coat a metallic glass with thin film form of BMGs onto the substrate of biomedical devices might solve this problem. For future work in this field, metallic glass coatings techniques with thin film form of BMGs including in vitro and in vivo studies are recommended.
Round 2
Reviewer 1 Report
None needed
Author Response
Point to point responses to the reviewers’ comments
We are grateful for very helpful comments. We understand that English is not the authors’ mother tongue and the sentences are not sophisticated and might have some minor grammatical mistakes. At the same time, we have published more than 40 peer-reviewed original articles without English proofread by native speakers, and we believe that this article meets the requirements of international standards. We can follow a proofreading by editors or reviewers, so please let us know all the expressions that should be revised and provide the better expressions clearly.
Reviewer 1
Point number 1.
Reviewer’s comment
None needed
Our responses
We appreciate your acceptance.
Text change
None
Reviewer 4 Report
-
Author Response
Point to point responses to the reviewers’ comments
We are grateful for very helpful comments. We understand that English is not the authors’ mother tongue and the sentences are not sophisticated and might have some minor grammatical mistakes. At the same time, we have published more than 40 peer-reviewed original articles without English proofread by native speakers, and we believe that this article meets the requirements of international standards. We can follow a proofreading by editors or reviewers, so please let us know all the expressions that should be revised and provide the better expressions clearly.
Reviewer 4
Point number 4.
Reviewer’s comment
-
Our responses
None.
Text change
None
