How Does the Biocompatibility of Molybdenum Compare to the Gold Standard Titanium?—An In Vivo Rat Model

Round 1

Reviewer 1 Report

The manuscript entitled "How does the biocompatibility of molybdenum compare to the 2 gold standard titanium- an in vivo rat model" reports the Mo and Ti implants in Wistar rats to evaluate the biocompatibility and degradation behavior. There are some suggestions to be included for further improving the manuscript.

Major comments

Line 477 - It has been reported that very low degradation rates of molybdenum samples compared to earlier studies (Ref: 34 and 27). In these references, corrosion behavior analysis, assessment of the amount of degradation , Mo concentration analysis via ICP OES etc have been conducted to obtain a conclusive evidence about the degradation behavior of Mo. However in the present study, metallographic cross section in the provided scale (with pores and cracks already present in samples) will not yield similar conclusions on degradation behavior. This shall be elaborated.

Fig 4a: Usually Ti and its alloys in polished state possess a silvery white appearance, In Fig 4a, it is darker. It is suggested to mention the reason for this change in appearance. 

Discuss the effect of pores and cracks present in the SLM Mo on the in vivo degradation behavior of the alloy.

Line 137 and 145 - The final polishing procedure for molybdenum sample is plasma polishing and for Ti it is microglass pearl blasted, which is standard. Will there be any influence of this different polishing behavior on the in vivo behavior?

Minor suggestions

Introduction section, there are so many small paragraphs. It is recommended to combine these small paragraphs for an improved readability.

Line 194 and 135 : Recommended to use same dimensions

Fig 7: Units are missing in axis labels

Line 78 - Change to either polylactide or polylactic acid

Line 82 - It is recommended to restructure this sentence.

Line 105- Change to Selective Laser Melting (SLM)

Title: I would suggest a question mark (?) at the end of the title

  

Author Response

Please see the attachment. 

Author Response File: Author Response.docx

Reviewer 2 Report

I would recommend the editor reconsiders this article pending Major Revisions. I find the results of this study are well presented and would be of interest to the readership of Applied Sciences. Greater detail is still required in respect to the methodology.

Before the next round of revisions, I would expect the authors to complete the conflict of interest’s declaration. My comments are listed below:

41: What do the authors means by “highest demands”? Demands of what?

46: What does “good” stability look like?

63 – 76: These paragraphs lack detailed description. Authors should state advantages and disadvantages of other materials used. For example, more than just PGA being considered with regards to polymer derived bioresorbable implants.

88: Authors cannot state the term “proven” without a reference. Nor would I agree that molybdenum has been proven. I do agree it is a promising alternative however it cannot be termed “proven”.

135: The authors should include more information regarding the production of molybdenum. Example being more detail regarding the “selective laser melting process”.

138: What plasma parameters were used?

150: What Gy?

166: Rat hair should be removed from surgical sites as it harbours bacteria and prevents thorough cleansing of the incision site. How was the hair removal performed in this study?

Figure 7: No X and Y axis labels.

293: Which group did this animal belong to?

Figure 11: What images are these? How were they taken?

443: Did you run any SEM or other materials quantification to understand the degradation of the implants directly?

471: Must explain what materials characterisation was performed (SEM, EDX etc).

Overuse of conjunctive adverbs throughout makes the manuscript difficult to read. This is especially notable in the abstract. 

Author Response

Please see the attachment. 

Author Response File: Author Response.docx

Reviewer 3 Report

This is a good and interesting paper.Molibdenum is considered to be a promosing " new"biodegredable material in the implantology.In ths animal experiment no significant inflammatory reaction of the Molybdenum versus Titanium could be detected.The study demonstrate in a statistically large cohort,that Molybdenum implant do not cause any major probeme in the health of animal,when compared with the Titanium.

Author Response

Dear Reviewer, 

Thank you very much for your review, which we are very pleased to receive. 

Kind regards
André Toschka 

Round 2

Reviewer 1 Report

The authors have clearly addressed the comments and the manuscript is recommended for publication. One small doubt still exists, which will also arise in readers in bioresorbable material research community: 

Since the application is intended for bioresorbable implants, what will be the estimated total degradation time for molybdenum for the specific application? In the present work less degradation is observed due to capsule formation. Hence kindly discuss about considering this apsect while designing a bioresorbable material, which will behave differently in vivo and in vitro.

 

Author Response

Thank you very much for this good advice. 

Bone healing, e.g. after a fracture, is subject to complex remodeling processes and depends above all on the body region. Complete ossification is usually observed after 6 weeks. Complete stability is normally assumed after about six months, especially in the field of maxillofacial surgery. A good guideline is that the implant should bear load for 3-6 months and then have fulfilled its function.

In our in vitro experiments, we were able to show that molybdenum sheets under physiological conditions exhibited a mass loss of approx. 20% after 6 months. Thus, a relevant loss of stability already occurs, which in theory would fit well with the time needed for bone stability to be regained. Furthermore, this rate of degradation indicates that there is a reasonable expectation that a molybdenum-based implant will degrade within a clinically relevant time frame, e.g. 1-2 years.

However, the degradation rates for encapsulated molybdenum are so low (<< 1µm/year) that degradation will not occur in humanly achievable time. Animal studies in other tissues (aortic wall) have shown degradation rates corresponding to a few tens of µm/year at most. Unless future experiments in other tissues show significantly higher rates, molybdenum implants should therefore not exceed structural sizes of 100 µm, maximum 150 µm, to allow degradation in a few years. The high strength and stiffness of molybdenum is advantageous here, allowing much thinner structure sizes than magnesium implants, for example.

As discussed earlier, it will therefore be important in follow-up experiments to find out how different environments affect the degradation of molybdenum. Furthermore, the design of the molybdenum implants will be very important. 

Therefore, implants will have to be designed as molybdenum to have the stability losses at the required times, for example, through predetermined breaking points.

We have added the above aspects in the discussion. 

Reviewer 2 Report

All of my comments have now been addressed.

Minor editing required. 

Author Response

Dear Reviewer,

Thank you very much for your review, which we are very pleased to receive.

Kind regards
André Toschka