Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript entitled "Efficacy and Safety of a Bioinspired Chitosan-catechol/Gelatin Hemostatic Patch versus TachoSil in Hepatectomy: A Randomized Noninferiority Trial" submitted by Kim et al reports the evaluation of the efficacy and safety of a novel bioinspired adhesive previously developed, the chitosan-catechol/gelatin hemostatic biomaterial - InnoSEAL Plus DL - and its comparison with TachoSil. Then the authors performed multicenter, randomized, single-blind, active-controlled, parallel-group noninferiority trial comparing the InnoSEAL Plus DL with TachoSil in adults undergoing hepatectomy with persistent oozing despite primary hemostasis, specially in the 3 minutes after device application. The article is well aligned with the field of biomaterials science, and the discussion reflects the achievements obtained during the research. However, it includes only 23 scientific references, which is insufficient to adequately support the results and the overall discussion. The number of references should be increased to at least 35-40, ensuring proper coverage of the relevant literature topics in the biomedicine field.

The Discussion section presents interesting results obtained by the authors. However, the Conclusions section is poorly developed, consisting of only four lines of text (lines 407 - 410). For this reason, it should be revised and expanded by the authors.

Major revisions:

- Significantly increase the number of references; additional citations should be incorporated into both the Introduction and the Results/Discussion sections.

- Revise the Conclusions section, as it is poorly written and too short.

- The authors should include in the Results or Discussion section a Figure or Scheme that graphically represents the interesting aspects of InnoSEAL Plus DL biomaterial, to help readers better understand the system (hemostatic mechanism) when reading the article.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Although the title of the research is strong and relevant, certain areas of the manuscript require a thorough revision before it can be considered for publication. Please address the following points for improvement:

1. Provide a detailed justification for the non-inferiority margin, which is stated to preserve 50% of the treatment effect.
2. 100% success rate in both arms is highly unusual; please clarify the bleeding severity grading system and ceiling effect implication.
3. On page 4, homeostasis is defined as the subjective cessation of bleeding. Do also include objective criteria
4. Device application is described briefly, without any standardisation of pressure applied and mention of operator variability. Define standard operating protocol and clarify reproducibility.
5. The manuscript requires substantial improvement in terms of formatting and language quality, as it currently does not meet the standards expected for a scientific publication. There are multiple instances of incomplete and placeholder information, improper word breaks and hyphenation, inconsistent terminology usage, and irregular spacing throughout the text.

Author Response

Please see the attachment. 

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Author,

The manuscript entitled “Efficacy and Safety of a Bioinspired Chitosan-catechol/Gelatin Hemostatic Patch versus TachoSil in Hepatectomy: A Randomized Noninferiority Trial” has been carefully evaluated. The study addresses a clinically relevant topic and presents a well-structured randomized design. However, several methodological and interpretational issues require clarification and further discussion. My comments are listed below.

1. Surgeons were not blinded, and the primary endpoint is visually assessed. Please discuss the potential risk of observer bias.
2. The definition of “hemostatic success” is subjective and based on visual assessment. Please clarify how this was evaluated and whether any objective criteria or independent assessment was used.
3. The term “persistent oozing” is not clearly defined. Please provide clear and reproducible criteria for this condition.
4. The 100% success rate in both groups limits the ability to compare treatments. Please discuss this limitation and its impact on the conclusions.
5. The non-inferiority margin (−19.4%) needs stronger clinical justification, especially considering the very high success rates observed.
6. Protocol deviations (e.g., use of tranexamic acid) were reported. Please explain their potential impact on the results and provide additional clarification.
7. Concomitant procedures were more frequent in one group. Please explain this imbalance and discuss its possible effect on outcomes.
8. Safety data are presented, but the analysis is limited. Please provide a clearer interpretation of adverse events, including their clinical relevance and possible relation to the device.
9. No subgroup analyses were performed. Please consider adding subgroup analysis (e.g., cirrhosis, surgical approach) or discuss this limitation.
10. The effect of different surgical techniques (open vs laparoscopic) was not evaluated. Please clarify or discuss.
11. Primary hemostasis methods varied between patients. Please discuss how this may affect the results.
12. The difference in time to hemostasis is minimal. Please discuss its clinical relevance.
13. The rebleeding endpoint could not be analyzed due to no events. Please comment on this limitation.
14. The follow-up period is limited to 30 days. Please clearly state this limitation in terms of long-term safety.
15. The influence of sponsor involvement should be more clearly acknowledged and discussed.

Best regards,

Author Response

Pease see the attachment.

Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

Authors compared InnoSEAL Plus DL, a bioinspired chitosan-catechol/gelatin hemostatic patch, with TachoSil for controlling hepatic oozing during hepatectomy. Both achieved 100% hemostatic success within 3 minutes, with similar safety profiles. The study highlights InnoSEAL Plus DL as a viable alternative to fibrin sealants, particularly in settings favoring synthetic materials.

1. How was the noninferiority margin of −19.4 percentage points clinically justified?
2. Could you elaborate on the rationale for excluding patients with major bleeding after primary haemostasis?
3. What measures were taken to ensure standardised application pressure during device use?
4. Can you discuss potential long-term effects of InnoSEAL Plus DL, such as tissue adhesion or degradation profiles?
5. Could you provide more details on the handling characteristics of InnoSEAL Plus DL compared to TachoSil?
6. How do the findings translate to other surgical fields beyond hepatectomy?
7. Were there any differences in patient-reported outcomes between the two groups?
8. What steps were taken to ensure consistency in the assessment of haemostatic success across surgeons?
9. Were there any unanticipated adverse events not captured in the predefined safety endpoints?
10. Could you elaborate on the implications of the study’s short follow-up period (30 days) for assessing late complications?
11. How might the study design be adapted to evaluate InnoSEAL Plus DL in more severe bleeding scenarios?

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

All problems have been solved.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Author,

The revised manuscript entitled “Efficacy and Safety of a Bioinspired Chitosan-catechol/Gelatin Hemostatic Patch versus TachoSil in Hepatectomy: A Randomized Noninferiority Trial” has been carefully evaluated. The authors have adequately addressed the reviewer comments, and the manuscript has been significantly improved in terms of methodological clarity, interpretation of the findings, and discussion of limitations. The revised version is clearer, more balanced, and scientifically strengthened. Overall, the manuscript is considered suitable for publication in its current form.

Best regards,

Reviewer 4 Report

Comments and Suggestions for Authors

Authors have addressed the comments to my satisfaction. No further corrections required.