Gentamicin-loaded silk/nanosilver composite scaffolds for MRSA-induced chronic osteomyelitis

Methicillin-resistant Staphylococcus aureus (MRSA) often induces chronic osteomyelitis and then bone defects. Here, gentamicin-loaded silk/nanosilver composite scaffolds were developed to treat MRSA-induced chronic osteomyelitis. AgNO3 was reduced with silk as a reducing agent in formic acid, forming silver nanoparticles in situ that were distributed uniformly in the composite scaffolds. Superior antibacterial properties against MRSA were achieved for the composite scaffolds, without the compromise of osteogenesis capacity. Then gentamicin was loaded on the scaffolds for better treatment of osteomyelitis. In vivo results showed effective inhibition of the growth of MRSA bacteria, confirming the promising future in the treatment of chronic osteomyelitis.

with osteoblast, and antibacterial properties against MRSA. This study is interesting, and the manuscript can meet the standard of the journal. I would like to recommend it for publication if the authors can address the following points, listed on a chronological basis rather than by importance.
Your data in figure 8, does not show a significant difference between SF+G and SF-AgNPs+G. please provide more explanation how addition of AgNPs can improve the results. One of the major clinical concerns is how this composite scaffolds perform over a long period of time? how long the effect of gentamicin will last in the composite scaffold. Similarly, how long the effect of AgNPs will last in the composite scaffold? Please discuss more the performance of the scaffold over time. It is claim in the following reference that the optimum pore size is more than 300 m, so since the pore size in this study is between 130 and 460 μm, do you see any significant differences between pore sizes? (Karageorgiou V. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005) And does 300-micron pore sizes and higher give better results specially with respect to bone formation and angiogenesis. What would be the clinical effect of pore size? What would be the clinical effect of inhomogeneous porous structure? Can AgNPs be used with other natural hydrogels like gelatin and collagen as well? What percentage of cells exhibits elongated morphology? Does the present method have a better dispersion of AgNPs compared to the previous similar methods?

07-Mar-2019
Dear Dr Zhang, On behalf of the Editors, I am pleased to inform you that your Manuscript RSOS-182102 entitled "Gentamicin-loaded Silk/nanosilver composite scaffolds for MRSA-induced chronic osteomyelitis" has been accepted for publication in Royal Society Open Science subject to minor revision in accordance with the referee suggestions. Please find the referees' comments at the end of this email.
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I note that you are correct and "degumming" is indeed an obscure but real word. For example, according to the Oxford English Dictionary, commercial degumming machines could be purchased all the back in the 1880s. Feel free to leave in that word if you desire.
I look forward to reading your revised manuscript.
Reviewer comments to Author: Reviewer: 1 Comments to the Author(s) I have read through the manuscript. Overall, this is an interesting paper with an aim to fabricate Silk/nanosilver composite scaffolds loaded with gentamicin for treating MRSA-induced chronic osteomyelitis. In this paper, the dissolving solvent of formic acid and silk as reducing agents for in situ conversion AgNO3 into silver nanoparticles which were uniformly distributed in the resulting composite scaffolds. In vitro and in vivo studies showed the good biocompatibility with osteoblasts, superior antibacterial properties against MRSA, and effectively treat chronic osteomyelitis. The manuscript can be considered for publication after some minor revisions. 1.
The language should be checked carefully to avoid clerical errors, such as the word "degumming" in Page 5, and the disagreement of English tenses throughout the manuscript.

2.
Although the authors claimed the superior antibacterial properties against MRSA in vitro, and effectively treatment on chronic osteomyelitis in vivo for Silk/nanosilver composite scaffolds, the inhibition zone test could not support it, as shown in Fig.5.

Reviewer: 2
Comments to the Author(s) In this paper SF-AgNPs composite scaffolds loaded with gentamycin are designed to treat MRSAinduced chronic osteomyelitis. To this end, the scaffolds mainly require showing biocompatibility with osteoblast, and antibacterial properties against MRSA. This study is interesting, and the manuscript can meet the standard of the journal. I would like to recommend it for publication if the authors can address the following points, listed on a chronological basis rather than by importance.
Your data in figure 8, does not show a significant difference between SF+G and SF-AgNPs+G. please provide more explanation how addition of AgNPs can improve the results. One of the major clinical concerns is how this composite scaffolds perform over a long period of time? how long the effect of gentamicin will last in the composite scaffold. Similarly, how long the effect of AgNPs will last in the composite scaffold? Please discuss more the performance of the scaffold over time. It is claim in the following reference that the optimum pore size is more than 300 m, so since the pore size in this study is between 130 and 460 μm, do you see any significant differences between pore sizes? (Karageorgiou V. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005) And does 300-micron pore sizes and higher give better results specially with respect to bone formation and angiogenesis. What would be the clinical effect of pore size? What would be the clinical effect of inhomogeneous porous structure? Can AgNPs be used with other natural hydrogels like gelatin and collagen as well? What percentage of cells exhibits elongated morphology? Does the present method have a better dispersion of AgNPs compared to the previous similar methods?

02-Apr-2019
Dear Dr Zhang, I am pleased to inform you that your manuscript entitled "Gentamicin-loaded Silk/nanosilver composite scaffolds for MRSA-induced chronic osteomyelitis" is now accepted for publication in Royal Society Open Science.
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