Cell Supported Single Membrane Technique for the Treatment of Large Bone Defects: Depletion of CD8⁺ Cells Enhances Bone Healing Mechanisms During the Early Bone Healing Phase

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The submitted manuscript is well written and follows a logical hypothesis. The only critisim relates to the control groups utilised. Several studies have used in bone regeneration mesenchymal stem cells isolated from the bone marrow that consitute the pool containing the main regenerative cells for bone regeneration. Removing only CD 8+ cells is a logical approach, but it would have been interesting to see what would have been the outcome if ONLY MSC have been added. 

Author Response

Response to Reviewer Comments

Dear Reviewer,

Thank you very much for giving us the opportunity to improve our manuscript. Please find attached our responses to your comments.

We hope that the revised version meets your expectations and look forward to your positive response.

Kind regards,

Marissa Penna-Martinez

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

In this work, it is described the in vivo evaluation of the cell supported single membrane technique. Major revisions are needed before publication:

 

1. In the Introduction section it is said that human acelular dermis seeded with bone marrow mononuclear cells enhance the healing of bone defects and also that this procedure significantly impairs the healing of bone defects (lines 50-55). Authors should re-write this paragraph and include relevant references to support the information provided.

 

2. It must be specified the procedure for the obtention of the cancellous bone graft from donor rats as well as the human acelular dermal matrix.

 

3. The selection of 3 and 7 days to study the early phase of bone healing should be explained in the Materials and Methods section as this process encompass several months so longer times could be selected as early phase points.

 

4. The detection of several mediators only at day 7 (namely RGM-A, IL-6 and osteoprotegerin) should be further discuss regarding their specific function in the bone healing process.

 

5. The described approach have reported good results in vivo so it would be valuable compare it in terms of outcomes with respect to the Masquelet-induced membrane technique.

Author Response

Response to Reviewer Comments

Dear Reviewer,

Thank you very much for giving us the opportunity to improve our manuscript. Please find attached our responses to your comments.

We hope that the revised version meets your expectations and look forward to your positive response.

Kind regards,

Marissa Penna-Martinez

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Authors have addressed all the concerns previously raised by the reviewer.