Review Reports

Round 1

Reviewer 1 Report

This manuscript provides an interesting examination of PEMFs and galvanotaxis DC EFs treatment in enhancing synovial cell-mediated cartilage repair. In general, this is an interesting work. However, there are some errors throughout the paper, especially in the presentation of experimental data. This manuscript needs to be carefully revised before it can be considered for publication.

 1.        Indicative probability values are missing in Figure 5I.

2.        Standard deviation and probability values in Figure 8E are missing. The scaling of Figure 8B and D seems to be different, as the authors claimed that the scale bars of these images are the same. The resolution of Figure 8A-D is too low for identification, and high-resolution images should be provided here.

3.        Figure 9 and its caption are unreadable and the authors need to carefully prepare the graphics in the manuscript.

4.        Scale bars are missing in Figure 12.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

The paper presents the effect of pulse electromagnetic field therapy and direct current electric field modulation on migration of fibroblast-like synoviocyte to promote cartilage repair. This topic is interesting, but the paper should be significantly improved before acceptance for publication.  

My comments are as follows:

The authors have developed a stem cells-based method that is trying to guide the autologous FLS migrate to articular cartilage defect to promote articular defect healing. However, some clinical used treatments like microfracture and osteochondral graft were mentioned. I suggest the introduction in the article should be more focused on discussion of the cell-based methods like ACI or MSCs based therapies. Please revise.

Line 74-77, the sentence of “The key to address....... envelops the diarthrodial joint.” I do not understand what the authors are supposed to describe. Please revise.

 In Figure 9, two figures were shown and figure legend is not able to be read, the authors should check the format of the article more carefully before submission.

 The quality of figures and figure legends are poor, suggest to re-organize all of the figures into higher quality ones. The description of figure legends should be written clearly and is more easy to understand.

In Figure 10, The authors mentioned that the FLS and chondrocytes migrations were checked. However, markers of FLS and chondrocytes were not detected. The magnification of the figure is too small, it is not easy to see any detail from this figure.

PEMF has been used for bone regeneration. Since the authors applied PEMF for cartilage repair, the possible side effect of PEMF on osteogenesis of MSCs should be discussed.

The discussion is complicated and tedious, not concise enough. Please revise discussion part.

 

 

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

1.      Is there any significant difference in treatment effect between CTL and PEMF groups in Figure 5? please add * in figure 5. Besides, how many repetitions are there (n=?) in the experiment? please add it.

2.      Please add * in Figure 8 E, F.

3.      Please rearrangement Figure 9, images were overlapped.

4.      Pleaser provide CD markers staining results of chondrocyte and synoviocytes you isolated from discarded (IACUC-exempt) bovine calf knee joint?  

5.      Will the DC EF influence cell viability in the study? Did the authors check the cell viability by WST, MTT or live/dead staining?

6.      In study 5, does the cells in PEMF group have better GAG synthesis efficiency?

7.      Did the cells in PEMF group synthesize more type II collagen in cartilage constructs? (collagen type will influence the quality of ECM)

8.      Please check more proteins or proteoglycans in cartilage matrix, such as type X collagen, aggrecan.

9.      Please add G, H, I, J in Figure 12. And what is the white circle means in the figure? Besides, there is no scale bar in figure (but the figure caption indicated scale bar = 400 μm)

10.  Please add the exact PEMF parameters you suggested in clinical use or lab use for cartilage repaired in abstract (according to the study)

 

11.  Would PEMFs and galvanotaxis DC EF treatment possess some limitation for clinical use?

 

 

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

In the revised manuscript, the authors corrected the mistakes and modified the data to further support their conclusions. They also responded to the comments point-by-point. The quality of the revised manuscript was improved and could be accepted for publication.

Reviewer 2 Report

All my questions have been properly answered.

Reviewer 3 Report

Authors have re-checked the manuscript, made appropriate corrections and added more crucial information, such as live/dead staining data and qPCR results to strength the concept of PEMF and galvanotaxis DC EF modulation for improving cartilage repair and healing. This study is suitable for publication in Applied Sciences.