Evaluation of a Multifunctional Polyvinylpyrrolidone/Hyaluronic Acid-Based Bilayer Film Patch with Anti-Inflammatory Properties as an Enhancer of the Wound Healing Process

Round 1

Reviewer 1 Report

The manuscript "Evaluation of a multifunctional polyvinylpyrrolidone/hyaluronic acid-based bilayer film patch as an enhancer of the wound healing process with anti-inflammatory properties" is of very good scientific quality and very well written.
It represents a continuation of a previous study (published in 2019), which proposed the fabrication of a PVP / hyaluronic acid-based bilayer wound dressing material using two water-based scalable approaches.   The scientific, medical and industrial interest for this type of material being very high, the current manuscript explores the multifunctionality of the PVP-based multifunctional bilayer material and more specifically, its effect in several "in vitro" and "in vivo" mice models.
  The introduction presents a pertinent and up-to-date overview of the literature data from the last 10 years.
  The applied methodology is perfectly chosen and very well explained in the text.
  The experimental results are presented in synthetic figures and tables, based on statistical analyses and on a very good and clear imagery.
  The interpretation of the results is pertinent and validates the real potential of polyvinylpyrrolidone / hyaluronic acid-based bilayer wound dressing for the treatment of various skin damages from acute to chronic.   The Conclusions and the Abstract are succinctly presenting the context and the main experimental results validating the use of PVP / hyaluronic acid-based bilayer wound dressing for the medical treatment of skin injuries.
    I fully recommend this manuscript for publication as it is.  

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

My main concern is the originality of the idea of the work and novelty of the methodology. In general, the idea is not new, and the methodology, i.e., fabrication, is not new, published by the authors in another paper. “Polyvinylpyrrolidone/hyaluronic acid-based bilayer constructs for sequential delivery of cutaneous antiseptic and antibiotic” (Chemical Engineering Journal).

Comment 1:

The idea of the active wound healing dressing is not new in literature. There are many reports on using 3D printing to make active dressing, eg, “Electrospun PLGA membrane incorporated with andrographolide-loaded mesoporous silica nanoparticles for sustained antibacterial wound dressing” (Nanomedicine). The authors need to discuss the novelty of their work in the context of the existing literature.

Comment 2: 

The study identified two missing functions with the existing literature, namely (i) monitoring the state and (ii) modulating the release. They proposed a two-layer structure. Please give more detailed explanation of why this structure can achieve the two missing functions in literature.

Comment 3:

There are some other ways to build a career for loading drug and releasing, e.g. “Engineering Synthetic Artificial Pancreas Using Chitosan Hydrogels Integrated with Glucose-Responsive Microspheres for Insulin Delivery” (Materials Science and Engineering: C). The authors need to compare with these other approaches that the printing approach in terms of the benefits that can be brought by their approach.

Comment 4:

Quoted from the manuscript: “Moreover, age-related immune deficiency, hypoxia, immobility, and pathological conditions such as hyperglycemia due to diabetes and obesity[9,10] can stem the success of the healing.” Comment: what does it mean by “stem”?

Comment 5:

Quoted from the manuscript: “Therefore, the design of an ideal material/formulation including all the mentioned requirements is still a great challenge for researchers.”

Comment: I feel that the above statement is too general. The authors may need to be specific to give details of analysis of the literature related to the use of 3D printing of dressing. I feel that the authors have not exhausted study of the literature, e.g., “3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels” (Polymer), “Tyrosinase-doped bioink for 3D bioprinting of living skin constructs” (Biomedical Materials). The authors need to make critical analysis of these works in the aspects of material, system, and function, which may then lead to a strong motivation for their work.

Comment 6:

Quoted from the manuscript: “In a recent study[1], we presented the fabrication of a PVP-based multifunctional bilayer material using two water-based scalable approaches.”

Comment: I am confused by the above statement, which seems to say that the novelty of their work is fabrication. Please clarify whether it is a contribution in the system or in fabrication technique. If it is the system, whether the principle for the system to operate is new or whether the material used in the system is new.

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

The manuscript "Evaluation of a multifunctional polyvinylpyrrolidone/hyaluronic acid-based bilayer film patch as an enhancer of the wound healing process with anti-inflammatory properties" by Contardi, provides relevant information on the application of polyvinylpyrrolidone/hyaluronic acid patches as an enhancer of the wound healing process with anti-inflammatory properties. However, the authors could improve the manuscript by clarifying the following points:

Positive controls (drugs) should be added in each of the assays to compare the cytotoxicity and biological activities of the polyvinylpyrrolidone/hyaluronic mixture.

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

I am satisfied with the revision with rebuttal.