Effect of Surface Treatment of Multi-Directionally Forged (MDF) Titanium Implant on Bone Response

Round  1

Reviewer 1 Report

This submission is devoted to the study of MDF titanium implants etched in different chemicals on the bone response. The authors prepared three different types of Ti and MDF-Ti surfaces by chemical etching. They studied morphology and topography of the surfaces. In vitro (SBF immersion) and in vivo (histological and histomorphometrical observation) experiments also were carried out. The results showed that Acid or Alkali-heat treatment of MDF-Ti is a useful method for improving bone response.

Surface modification of titanium implants is very actual and important task for study now. The manuscript is written clearly and well organized. But the manuscript has a lot of disadvantages.

1)     Common remarks

Quantitative analysis of the results is poor. Especially for bone response. Only one quantitative biomedical parameter (BIC) was studied. I am not specialist in this area but I know that there are many methods for in vitro and in vivo quantitative characterization of implants (assessment of cells adhesion, proliferation, differentiation, removal torque etc.) The lack of quantitative characteristics leads to difficulties in comparing experimental results with the literature. Consequently, the perspectives of authors approach to improving bone response is not obvious.

Maybe this is not guilty of authors but the main conclusions are evident and expected. For example, they state that difference in surface morphology of Ti and MDF-Ti after etching is caused by difference in grain size. It is true but evident. In my opinion the manuscript lacks unexpected new results or a non-standard or original approach to their interpretation.

2)     Introduction

The introduction can be more relative to the current research. Now it contains too much discussion about elastic modulus and stress shielding etc. It is important issue for implant but authors don’t study the mechanical properties of implant in current research! The surface properties (composition, topography, wettability…) of implants are more important but authors should describe these aspects more thoroughly and clear.

What was the motivation for study? From the presented introduction it is not entirely clear why to carry out surface treatment by alkali and heat treatment? Why acid treatment is not enough if it working well? And finally the main question - Why is it necessary to develop new implants with a modified surface?

How much does MDF improve the mechanical properties of titanium (several times or maybe several percents)? You claim that «The ultimate tensile strength of MDF-Ti is more than 1 GPa». But what is the tensile strength for conventional Ti? Authors should mention this value.

3)     Results and Discussion

At the SEM pictures, the authors mark special areas such as nanoscale dimples. These features are very difficult to distinguish. If the authors have a higher magnification SEM for these areas, then they could be shown on the insets or supplementary file.

The authors used a non-standard method of studying topography. Why did not they used AFM? Usually for describe the topography average mean value of surface roughness (Ra) or root mean square roughness (RMS) is used. The authors used Sdr and Sa. They are not standard. Therefore it is very difficult to compare experimental results with literature data. I would advise describing these values (Sdr and Sa) in more detail in the experimental part. Write about how they are calculated or what is their physical meaning. In addition, it is necessary to indicate the dimensions of Sdr and Sa in tables 2 and 3.

Why did the authors use SD values in parentheses (at the tables) but not use ±?

It is very strange that contact angles<0. How is it possible?

Authors stated (page 10 line289) that «More developed trabecular bone was observed around MDF-Ti implants for the Alkali-heat specimen». What is part of this figure? Maybe it is worth to mark this area in the picture?

Authors stated that «Previously, the bone response of an as-machined MDF-Ti implant was evaluated by implantation into the cortical bones of rabbits [22]. The implants were cylindrically shaped.» But what were the results? What is the connection with current study?

The authors reasonably note that during heat treatment the grain size should increase (the end of the discussion). I believe that SPD titanium begins to lose its advantage in mechanical properties already at 400 °C. The authors annealed their samples (Alkali-heat) at 600 ° C. At the same time, the authors write that «however, it is predicted that MDF-Ti will be higher heat after thermal treatment.» What is the basis for this statement?

4)     Others

There is not a conclusion section! Therefore, it is unclear what the results and conclusions are the most important according to the author's opinion.

Despite all the shortcomings - the idea and content of the manuscript is interesting and it could be of interest to specialists working on titanium-based materials, SPD and the development of new implants. But the manuscript requires significant refinement. Firstly, the results are not well analyzed and understood. Secondly, it is not clear how good the results are and what are the prospects for the presented approach to the modification of the surface of implants.

Author Response

Thank you for your valuable comments. I revised the paper according to your comments.

I attach here the responses to your comments.

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors

The paper looks very interesting, congratulations, but you need some major revisions

Frist of all in the abstract describe what does  it means Multi-directional forging (MDFing)

How do you did it ? As surface treatments, acid (Acid), alkali without

25 post-heat (Alkali), and alkali with post-heat (Alkali-heat) treatments were employed.

Which surface are was used as control ? acid (Acid), alkali without

25 post-heat (Alkali), and alkali with post-heat (Alkali-heat)?

Are those implants commercialized for clinical use?

Are all those implants prepare specially for the rats study? Please explain

Commercially available screw-type pure Ti implants (: 1.5 mm; length: 3.0 mm; JIS 2 type; 99.9% 107 mass; Kawamoto Heavy Industries Co., Ltd., Takasago, Hyogo, Japan) and MDF-Ti implants (: 1.5 108 mm; length: 3.0 mm; JIS 2 type; 99.9% mass; Kawamoto Heavy Industries Co., Ltd., Takasago, Hyogo, 109 Japan)

Where didi you did the acid (Acid), alkali without

25 post-heat (Alkali), and alkali with post-heat (Alkali-heat). Please explain the Lab, City and Country.

Please explain the method reported by Raita et al.

Why the rats were 6 weeks old? Why you didn’t used older rats? Can you explain this please

Please explain Brand, Lab, City and Country

Surgical interventions were conducted under general anesthesia by an intraperitoneal injection of

163 ketamine hydrochloride (0.8 mg/kg) and medetomidine hydrochloride (0.4 mg/kg).

Statistical Analysis

I miss a non-parametric Test. Can you include please? By this test you can prove exactly the validation of your study

Please delete DOI

Sumitomo, N.; Noritake, K.; Hattori, T.; Morikawa, K.; Niwa, S.; Sato, K.; Niinomi, M. Experiment study on fracture fixation with low rigidity titanium alloy: plate fixation of tibia fracture model in rabbit. J Mater Sci Mater Med 2008, 19, 1581–1586. doi:10.1007/s10856-008-3372-y.

Miura, H.; Kobayashi, M.; Aoba, H.; Aoyama, H.; Benjanarasuth, T. An approach for room-temperature multi-directional forging of pure titanium for strengthening. Materials Science and Engineering: A 2018, 731, 603-608. https://doi.org/10.1016/j.msea.2018.06.060

Those references is too old. Please Update it

Hall, E.O. The deformation and ageing of mild steel: II characteristics of the Lüders deformation. Proc Phys Soc 1951, 64, 742–747.

Petch, N.J. The cleavage strength of polycrystals. J Iron Steel Inst 1953, 174, 25–28.

Author Response

Thank you for your valuable comments. I revised the manuscript according to your comments.

I attach here the responses to your comments.

Author Response File: Author Response.docx

Round  2

Reviewer 1 Report

The authors' responses are complete and reasonable. Changes are also made properly. I believe that the manuscript in its current form does not contain significant flaws and can be published.

P.S. There is the typo. Please correct the ref 18. The second author. I believe that Maxim is name, not surname. Please, check and correct