Predictive Estimates of Short-Term and Long-Term Results for Regenerative Rehabilitation of Local Articular Cartilage Defects in Synovial Joints
Round 1
Reviewer 1 Report
This is a very interesting and well built paper dealing with the in silico prediction of the regenerative rehabilitation process for articular cartilage. The study was based on a mathematical model which considers the diffusion of cells and nutrients into the defect area, when implementing cell technologies and tissue engineering structures under conditions of explants mechanical stimulation. Were performed numerical experiments by using a Matlab code based on the finite element method.
The content of this investigation is wide and for this reason I suggest some modification to complete the manuscript and to make it more readable:
1) In the scientific framework it could be appropriate to introduce some considerations on the natural synovial lubrication models, joining them with the specific scientific framework of the presented investigation;
2) It is necessary to reference the main equations presented in the mathematical model as well as to justify the adopted boundary conditions in (7) and (8);
3) To achieve the obtained results the Authors proposed many assumptions during the development of the mathematical model. Is it possible to give references for those?
4) Very few details were provided about the FEM model. It is necessary to improve it....where is Appendix 1?
5) It is necessary to make more incisive the Conclusions 8maybe by using bullets) and to underline the limitations of the investigation considering the proposed assumptions.
Author Response
1) In the scientific framework it could be appropriate to introduce some considerations on the natural synovial lubrication models, joining them with the specific scientific framework of the presented investigation;
Response: We added a paragraph to the manuscript explaining the features of AC as a living tribological system (see lines 102-108).
2) It is necessary to reference the main equations presented in the mathematical model as well as to justify the adopted boundary conditions in (7) and (8);
Response: In manuscript line 241, we have reference given to the literature in which the model equations (1) and (2) were first presented. In lines 337-338 and 348-355, we justified the accepted boundary conditions.
3) To achieve the obtained results the Authors proposed many assumptions during the development of the mathematical model. Is it possible to give references for those?
Response: The basis of the mathematical model used in this paper is the model first used by M. Lutianov [57], to which is reference given in line 241. In this model, the author also provided a rationale for the assumptions and limitations adopted, on the one hand, on the basis of known experimental data research, and on the other hand, on the basis of plausible reasoning.
4) Very few details were provided about the FEM model. It is necessary to improve it....where is Appendix 1?
Response: 1) We explained the motivation for using FEM to study a mathematical model represented by a complex system of non-linear partial differential equations, referring to the literature used (see lines 426-430, 435-438, and 762-766).
2) Appendix 1 is given at the end of the manuscript and begins on line 635.
5) It is necessary to make more incisive the Conclusions 8maybe by using bullets) and to underline the limitations of the investigation considering the proposed assumptions.
Response: As per your recommendation, we have clarified Conclusions (see lines 619-634).
Reviewer 2 Report
This is an interesting study about predictive estimates of short-term and long-term results for regenerative rehabilitation of local articular cartilage defects in synovial joints. I suggest it for publication after the following minor points are solved.
1. Line 44-47, one recent review (Advanced Materials 33 (18), 2005513) should be included to support such a claim.
2. What's the pore size of the cartilage? Does the pore size increase in the area of the defects?
3. It is better to compare the current model study to the real work.
Author Response
- Line 44-47, one recent review (Advanced Materials 33 (18), 2005513) should be included to support such a claim.
Response: We have taken into consideration your remark (see lines 56-58 and 665).
- What's the pore size of the cartilage? Does the pore size increase in the area of the defects?
Response: We have put the answer to your question in the manuscript (see lines 312-330)
- It is better to compare the current model study to the real work.
Response: Currently, there is an active search for new methods of osteoarthritis treating, but, unfortunately, effective solutions have not yet been found. Considering the performances of articular cartilage, as well as the complexity of the processes that ensure its homeostasis, functional and reparative regeneration, it is necessary to perform a very large number of experimental studies in order to achieve positive results. They can be reduced based on the results of in silico studies. Therefore, one of the goals for this work is to find ways to plan effective experimental studies of the regenerative rehabilitation processes for articular cartilage defects and to minimize their number.
