Emerging Trends in Curcumin Embedded Electrospun Nanofibers for Impaired Diabetic Wound Healing
, Manikandan Krishnan 1,*, Govindaraj Sabarees 2, Siddan Gouthaman 3, Veerachamy Alagarsamy 4,* and Viswas Raja Solomon 4,*Round 1
Reviewer 1 Report
In this review, the authors discuss the application of curcumin in wound healing. Overall, the paper reads well. The background is well-covered and adequately addressed, with good connectivity between the sections. However, the paper appears to describe more of curcumin’s broad wound-healing role than in diabetic wound healing, which is supposedly the paper’s main aim. Diabetic wounds do not follow the normal healing pattern and pose a significant clinical challenge. Therefore, I request that the authors focus more on the role of curcumin in restoring the functional responses in diabetic cells or wounds.
Important discussions, such as the potential of curcumin in restoring the impaired inflammatory and angiogenic activities in diabetic wound, is lacking. This could be filled in by discussing the mechanisms activated by curcumin in diabetic or hyperglycemic cells. Another major flaw of the paper is that the authors focussed too much on the physical properties of the curcumin-embedded nanofibers (section 7) rather than addressing the functional impact of the composite fibers on diabetic wound healing. Additionally, listing (table 2) the curcumin dosage and probably the pharmacokinetics would be more beneficial to the readers.
Which of the polymers described in section 7 is FDA approved? Are there any commercially available e-spun nanofibers clinically used for diabetic wound healing?
Author Response
In this review, the authors discuss the application of curcumin in wound healing. Overall, the paper reads well. The background is well-covered and adequately addressed, with good connectivity between the sections. However, the paper appears to describe more of curcumin’s broad wound-healing role than in diabetic wound healing, which is supposedly the paper’s main aim. Diabetic wounds do not follow the normal healing pattern and pose a significant clinical challenge. Therefore, I request that the authors focus more on the role of curcumin in restoring the functional responses in diabetic cells or wounds.
Important discussions, such as the potential of curcumin in restoring the impaired inflammatory and angiogenic activities in diabetic wound, is lacking. This could be filled in by discussing the mechanisms activated by curcumin in diabetic or hyperglycemic cells.
Response: We would like to thank the reviewer for their positive feedback and suggestion for improving the quality of the MS. We agree with most of the reviewer's suggestions and corrected/revised them. The diabetic wound healing pattern, which restores impaired inflammatory and angiogenic activities in diabetic wounds, has been incorporated into Sections 5.1 and 5.4, as well as revised Figure 4.
Another major flaw of the paper is that the authors focussed too much on the physical properties of the curcumin-embedded nanofibers (section 7) rather than addressing the functional impact of the composite fibers on diabetic wound healing.
Response: Agreed. In Section 7, the functional effect of the composite fibers on diabetic wound healing is discussed.
Additionally, listing (table 2) the curcumin dosage and probably the pharmacokinetics would be more beneficial to the readers.
Response: We agree with the reviewer's suggestion and added curcumin dosage and pharmacokinetics in Table 6 in the revised MS.
Which of the polymers described in section 7 is FDA approved?
Response: Agreed. Polymers approved by the FDA are described in Table 5.
Are there any commercially available e-spun nanofibers clinically used for diabetic wound healing?
Response: Clinically usable electrospun nanofibers for diabetic wound healing are not currently marketed.
Author Response File: 
Author Response.docx
Reviewer 2 Report
In this review, the authors summarize the potential properties and the most recent advances in the use of curcumin-loaded nanofibers for diabetic wound healing. After noting the need for a prevention-based approach to diabetic wound healing, the authors systematically describe curcumin, including its potential, biomedical applications, and effects on wound healing. In addition, they describe studies using various drug carriers, particularly electrospun nanofibers, to enhance curcumin bioavailability.
To the extent that I can appreciate it, I think the paper is a good work. Although one may need more evidence to demonstrate potential and application of curcumin. Figure 2 lists the biomedical applications of curcumin. But some applications, e.g. Asthma treatment, have not been discussed in the main text. I think it would be better to list referenced studies that demonstrate the effectiveness of curcumin for specific symptoms, like the authors did in Table 1. Similarly, Psoriasis in Figure 1 is also forgot to be mentioned in the main text. I think a table with listed reference may be helpful.
In the section of “Safety Profile of Curcumin” (lines 149 - 170), the authors have already worked very hard on demonstrating safe doses for several preclinical and clinical trials. The data is completed. But I think it would be concise to have a table to list them for different population.
One more thing, I think the authors should address more carefully. In line 250, the authors write curcumin prevents angiogenesis and slow the growth of tumors. However, the authors also write curcumin enhances angiogenesis in line 252. This conflicting result may stem from different mechanisms. I think the authors need a more detailed explanation.
In the end, there are some minor parts the authors should notice – for the first appearance of the abbreviations, the authors need to offer the full name. e.g. ECM in line 259, PCL in line 350 and STZ in line 362.
In summary, I think this paper needs some correcting before publication.
Author Response
Reviewer 2:
In this review, the authors summarize the potential properties and the most recent advances in the use of curcumin-loaded nanofibers for diabetic wound healing. After noting the need for a prevention-based approach to diabetic wound healing, the authors systematically describe curcumin, including its potential, biomedical applications, and effects on wound healing. In addition, they describe studies using various drug carriers, particularly electrospun nanofibers, to enhance curcumin bioavailability.
Response: We are highly thankful to the reviewer for their encouraging feedback and suggestion for enhancing the MS quality. We agree with most of the reviewer's suggestions and corrected/revised them.
To the extent that I can appreciate it, I think the paper is a good work. Although one may need more evidence to demonstrate potential and application of curcumin. Figure 2 lists the biomedical applications of curcumin. But some applications, e.g. Asthma treatment, have not been discussed in the main text. I think it would be better to list referenced studies that demonstrate the effectiveness of curcumin for specific symptoms, like the authors did in Table 1. Similarly, Psoriasis in Figure 1 is also forgot to be mentioned in the main text. I think a table with listed reference may be helpful.
Response: Agreed. Curcumin's biomedical applications are thoroughly explained, and inserted Table 2 with relevant references is included.
In the section of “Safety Profile of Curcumin” (lines 149 - 170), the authors have already worked very hard on demonstrating safe doses for several preclinical and clinical trials. The data is completed. But I think it would be concise to have a table to list them for different population.
Response: We agree with the reviewer's suggestion and incorporated the Safety Profile of Curcumin in Table 3.
One more thing, I think the authors should address more carefully. In line 250, the authors write curcumin prevents angiogenesis and slow the growth of tumors. However, the authors also write curcumin enhances angiogenesis in line 252. This conflicting result may stem from different mechanisms. I think the authors need a more detailed explanation.
Response: We agreed with the reviewer's feedback and corrected lines 250 and 252 in the revised MS.
In the end, there are some minor parts the authors should notice – for the first appearance of the abbreviations, the authors need to offer the full name. e.g. ECM in line 259, PCL in line 350 and STZ in line 362. In summary, I think this paper needs some correcting before publication.
Response: Agreed. Full form for the first appearance of all abbreviations given.
Author Response File: Author Response.docx
Reviewer 3 Report
This manuscript reviewed the potential properties and recent advancements in using curcumin-loaded nanofibers for diabetic wound healing. This review's summary states that several topical electrospun nanofiber formulations of curcumin are created to improve therapeutic benefits by steadily delivering curcumin to the injury site. Authors are suggested to addressed the following comments during revision.
1. In Figure 1, the actual images of these skin diseases that curcumin could treatment should be provided for a better understanding.
2. The publication date of these references should be provided in Table 1 and Table 2.
3. The relevant literatures should be noted in the outer ring of Figure 1 and Figure 2.
4. The advances and shortcomings of nanofibers in comparison with other curcumin carriers (e.g., nanoparticles, nanosheets) should be carefully discussed.
5. An eye-catching scheme should be created to emphasize the usage of curcumin-loaded nanofibers for diabetic wound healing.
Author Response
Reviewer 3:
This manuscript reviewed the potential properties and recent advancements in using curcumin-loaded nanofibers for diabetic wound healing. This review's summary states that several topical electrospun nanofiber formulations of curcumin are created to improve therapeutic benefits by steadily delivering curcumin to the injury site. Authors are suggested to addressed the following comments during revision.
Response: We would like to thank the reviewer for taking the time to review and provided positive feedback on our manuscript and recommending it for publication.
- In Figure 1, the actual images of these skin diseases that curcumin could treatment should be provided for a better understanding.
Response: Agreed. Figure 1 revised with actual images.
- The publication date of these references should be provided in Table 1 and Table 2.
Response: We agree with the reviewer's suggestion and publication dates for references provided in Table 1 and Table 6
- The relevant literatures should be noted in the outer ring of Figure 1 and Figure 2.
Response: Accepted. The relevant literature is noted in the outer ring of Figures 1 and 2.
- The advances and shortcomings of nanofibers in comparison with other curcumin carriers (e.g., nanoparticles, nanosheets) should be carefully discussed.
Response: Agreed. The advances and shortcomings of nanofibers in comparison with other curcumin carriers are discussed in Table 4.
- An eye-catching scheme should be created to emphasize the usage of curcumin-loaded nanofibers for diabetic wound healing.
Response: Accepted. An eye-catching scheme was created (Graphical abstract).
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
The reviewer's concerns are addressed and acceptance is recommended.
