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Peer-Review Record

Determination of Laser Parameters in Thermomechanical Treatment of Skin Based on Response Surface Methodology

Appl. Sci. 2024, 14(6), 2619; https://doi.org/10.3390/app14062619
by Hasan Mhd Nazha 1,*, Mhd Ayham Darwich 2,3, Basem Ammar 2,4, Hala Dakkak 5 and Daniel Juhre 1
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Reviewer 3: Anonymous
Reviewer 4: Anonymous
Reviewer 5: Anonymous
Appl. Sci. 2024, 14(6), 2619; https://doi.org/10.3390/app14062619
Submission received: 7 February 2024 / Revised: 13 March 2024 / Accepted: 18 March 2024 / Published: 21 March 2024
(This article belongs to the Section Optics and Lasers)

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear Authors,

here attached you can find my review.

Regards 

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Language is fine, minor editing is required.

Author Response

Dear respected reviewer,

Thanks for your insightful comments. 

Point 1: Line 56 please specify which wavelength was used and power applied. Line 63: please specify which wavelength was used and power applied. I think it will be useful if a discussion about the different kinds of lasers is added, which kinds of lasers are used in the medical field and which purpose and advantage instead of traditional techniques. Then a table summarizing this information could be added at the end of the introduction.

 

Response 1: The wavelength used and power applied have been specified at line 56 and line 63, addressing your comments. Additionally, a comprehensive discussion about the different kinds of lasers utilized in the medical field, their purposes, and advantages over traditional techniques has been incorporated into the introduction, as per your suggestion.

 

Point 2: Please specify which kind of laser has been used (model, factory etc). Which kind of optic fiber is used in this experiment and why?

 

It is important to clarify that our study is based on a numerical model without the direct application of laser beams on patients. Therefore, we have not utilized a specific laser model or fiber optic in our investigation. Our focus has been on simulating the structural changes occurring in the heat-affected region during the propagation of pulsed laser energy using computational methods, utilizing computational tools such as COMSOL Multiphysics.

 

Point 3: A scoping review that justifies the laser parameters you used and the laser device you choose is necessary.

 

We have taken your suggestion into account and have added a paragraph that justifies the use of the laser parameters chosen for our study:

 

"The 532 nm and 800 nm lasers enjoy wide applications across diverse medical fields due to their specific optical properties and interactions with biological tissues [6]. In dermatology and skin treatments, the 532 nm laser finds common use in addressing vascular lesions such as port wine stains and facial telangiectasia due to its effective absorption by hemoglobin, resulting in vascular coagulation [7]. Conversely, the 800 nm laser is applied in hair removal and skin rejuvenation treatments, targeting melanin in hair follicles and pigmented lesions [8]. Notably, in ophthalmology, the 532 nm laser is preferred for photocoagulation procedures in diabetic retinopathy and other retinal diseases due to its efficient absorption by hemoglobin [9], while the 800 nm laser is utilized in photodynamic therapy for conditions like age-related macular degeneration [10]. Specifically, both the 532 nm and 800 nm lasers play instrumental roles in laser surgery [11, 12], with the former being effective for tissue ablation such as laser lithotripsy for urological conditions [13], while the latter is suitable for soft tissue surgeries, including cutting, vaporization, and coagulation, owing to its deeper tissue penetration and lower water absorption compared to shorter wavelengths [12]."

References:

  1. Friedmann, D.P.; Timmerman, A.; Cahana, Z. Prospective Study of 532-Nm Picosecond Laser for the Treatment of Pigmented Lesions of the Face and Dorsal Hands. Dermatol. Surg. 2022, 48, 1215–1219, doi:10.1097/DSS.0000000000003602.
  2. Gao, L.; Qu, H.; Gao, N.; Li, K.; Dang, E.; Tan, W.; Wang, G. A Retrospective Analysis for Facial Telangiectasia Treatment Using Pulsed Dye Laser and Intense Pulsed Light Configured with Different Wavelength Bands. J. Cosmet. Dermatol. 2020, 19, 88–92, doi:10.1111/jocd.13179.
  3. Mongkol, V.; Preechaphonkul, W.; Rattanadecho, P. Photo-Thermo-Mechanical Model for Laser Hair Removal Simulation Using Multiphysics Coupling of Light Transport, Heat Transfer, and Mechanical Deformation (Case Study). Case Stud. Therm. Eng. 2023, 41, 102562, doi:10.1016/j.csite.2022.102562.
  4. Ghani, S.I.; Zunaina, E. Effect of 532 Nm Argon Laser Pan Retinal Photocoagulation on Corneal Thickness and Corneal Endothelial Cell Parameters among Proliferative Diabetic Retinopathy Patients. J. Diabetes Metab. Disord. 2021, 20, 561–569, doi:10.1007/s40200-021-00780-9.
  5. Wang, M.-F.; Yang, R.; Tang, S.-J.; Deng, Y.-A.; Li, G.-K.; Zhang, D.; Chen, D.; Ren, X.; Gao, F. In Vivo Realization of Dual Photodynamic and Photothermal Therapy for Melanoma by Mitochondria Targeting Dinuclear Ruthenium Complexes under Civil Infrared Low‐power Laser. Angew. Chem. Weinheim Bergstr. Ger. 2022, 134, doi:10.1002/ange.202208721.
  6. Wang, J.; Schuele, G.; Palanker, D. Finesse of Transparent Tissue Cutting by Ultrafast Lasers at Various Wavelengths. J. Biomed. Opt. 2015, 20, 125004, doi:10.1117/1.JBO.20.12.125004.
  7. Lange, B.; Jocham, D.; Brinkmann, R.; Cordes, J. Stone/Tissue Differentiation for Holmium Laser Lithotripsy Using Autofluorescence: Clinical Proof of Concept Study: STONE/TISSUE DIFFERENTIATION FOR LITHOTRIPSY. Lasers Surg. Med. 2017, 49, 361–365, doi:10.1002/lsm.22611.
  8. Fornaini, C.; Merigo, E.; Vescovi, P.; Bonanini, M.; Antonietti, W.; Leoci, L.; Lagori, G.; Meleti, M. Different Laser Wavelengths Comparison in the Second-Stage Implant Surgery: An Ex Vivo Study. Lasers Med. Sci. 2015, 30, 1631–1639, doi:10.1007/s10103-014-1623-3.

Reviewer 2 Report

Comments and Suggestions for Authors

Very extensive manuscript. Should be condensed to be readable.

Introduction: Should be condensed and revised . lines 121-135 should be splitted in both M&M and discussion part. A small paragraph should be added to show what is the need for this research and which answer is coveted by the results of this study. Lasers have a wide ranre of applications  in Dentistry (check recent refs DOI: 10.3390/ma1412337, doi: 10.15171/jlms.2019.52. )

Results : Although they are very analytical they should be condensed and major part should  be transfered to discusion part

Discussion is too short comparing to previous text, in this part it could be beneficial to add some comments for future research the ultra fast (femto second lasers) which are already used in opthalmology and have less thermal damage to surrounding tissues.

Conclusions: should be more accurate less narrative and should be in harmony with the results. Lines 545-551 should be deleted or added to discussion part 

Author Response

Dear Respected Reviewer,

Thanks for your insightful comments. 

Point 1: Introduction should be condensed and revised . lines 121-135 should be splitted in both M&M and discussion part.

 

Response 1: We have carefully revised the introduction as per your suggestions. The content from lines 121-135 has been appropriately condensed and distributed between the Methodology and Discussion sections for improved clarity and organization. We believe that these revisions enhance the flow of the manuscript and better articulate the significance of our research objectives..

 

Point 2: A small paragraph should be added to show what is the need for this research and which answer is coveted by the results of this study

 

Response 2: We have carefully addressed your suggestion by incorporating a highlighted paragraph in the revised version, delineating the necessity and anticipated outcomes of our research.

 

Point 3: Lasers have a wide ranre of applications  in Dentistry (check recent refs DOI: 10.3390/ma1412337, doi: 10.15171/jlms.2019.52

 

Response 3: We greatly appreciate your recommendation regarding recent reference on the diverse applications of lasers in dentistry. In the revised version, we have included the suggested reference to present the wide-ranging capabilities of lasers within the field of dentistry.

 

Point 4: Results: Although they are very analytical they should be condensed and major part should  be transferred to discussion part

 

Response 4: We have taken your suggestion into careful consideration and restructured the presentation accordingly. Recognizing the need for condensation and clarity, we have transferred the major analytical components to the discussion section while ensuring that the presentation remains comprehensive and accessible.

 

Point 5: Discussion is too short comparing to previous text, in this part it could be beneficial to add some comments for future research the ultra fast (femto second lasers) which are already used in opthalmology and have less thermal damage to surrounding tissues

 

Response 5: In our revised discussion section, we have highlighted the significance of femtosecond lasers in tumor ablation, emphasizing their role in minimizing thermal damage to surrounding tissues. This addition aims to underscore the importance of exploring advanced laser technologies, such as femtosecond lasers, in the context of tumor treatment.

 

 

Point 6: conclusions should be more accurate less narrative and should be in harmony with the results. Lines 545-551 should be deleted or added to discussion part

 

Response 6: We have thoroughly revised the conclusion section to ensure greater accuracy and alignment with our research findings. In particular, we have streamlined the narrative and focused on presenting concise and precise conclusions that reflect the outcomes of our study. Additionally, we have removed lines 545-551 and integrated any pertinent content into the discussion section for improved cohesion and clarity.

Reviewer 3 Report

Comments and Suggestions for Authors

The article presents the impact of laser wavelength (532 and 800 nm), intensity (1 to 2 W/mm2), and beam size on normal tissue, targeting the optimal treatment values via numerical simulations of temperature and mechanical variations using the finite element method ( COMSOL Multiphysics package). 

Similar results were published by P. Wongchadakul et al. (Simulation of temperature distribution in different human skin types exposed to laser irradiation with different wavelengths and laser irradiation intensities, Songklanakarin J. Sci. Technol. 41 (3), 529-538, 2019) using the same simulation package. Specifically, the temperature distribution in the skin after laser irradiation ( 532, 755, and 800 nm) and intensity (1, 1.5, 2 W/mm2) are evaluated; however, those are not discussed and referred to in the current manuscript. Additionally, some figures (Figures 1& 2) and Table 1 in both articles are similar to a large extent.

The article has numerous references to the  "impact of short-pulse laser radiation" (lines 14, 127, 129,475, 497, 537), although the duration of the laser pulse is not stated. This is an important factor because when femtosecond laser pulses are used, the ablation is characterized by negligible thermal effects on the material due to the very short laser pulse duration contrary to the ablation by several picosecond laser pulses, which imposes limitations on clinical applications.

Other issues

Differences in the laser parameters range: Abstract, line 16: "beam size ranged between 1 and 2 mm". But in Lines 140 & 200: 1-5 mm and Line 259, Table 2. Beam size: 0.5 to 3 mm.

Table 1: Intensity, I (W/mm2) (Epidermis) 1.0, 2.0; Abstract and Line 200:  Intensity 1-2 W/mm2) but in Table 2: I = Intensity (W/mm2) 1-5 (explanation is needed)

Undefined abbreviation FEA:  (line 240)

Grammar: Line 440: "As Figure (11-a) shows the average effect of the mentioned parameters on (Tmax), the figure shows that the response is not affected by (S and W)."

Confusing symbols: α is the absorption coefficient (line 220); α is the coefficient of thermal expansion of the tissue (line 238)

The preceding remarks indicate that the work is inappropriate for publishing in the Applied Sciences journal and that a substantial modification  is required.

Comments on the Quality of English Language

Grammar error: Line 440: "As Figure (11-a) shows the average effect of the mentioned parameters on (Tmax), the figure shows that the response is not affected by (S and W)."

Author Response

Dear Respected Reviewer,

Thanks for your insightful comments. 

Point 1: Similar results were published by P. Wongchadakul et al. (Simulation of temperature distribution in different human skin types exposed to laser irradiation with different wavelengths and laser irradiation intensities, Songklanakarin J. Sci. Technol. 41 (3), 529-538, 2019) using the same simulation package. Specifically, the temperature distribution in the skin after laser irradiation ( 532, 755, and 800 nm) and intensity (1, 1.5, 2 W/mm2) are evaluated; however, those are not discussed and referred to in the current manuscript. Additionally, some figures (Figures 1& 2) and Table 1 in both articles are similar to a large extent.

 

Response 1: We acknowledge the partial observed similarity between our study and the work by P. Wongchadakul et al. (2019). However, it's important to note that our primary objective was to reproduce values from a previously approved model, validated through comparison with experimental studies. Our initial reliance on this model provided a foundation upon which we expanded the analyzed range to enhance the robustness of our results.

Our main contribution lies in the application of the Box Behnken approach to determine optimal values that can induce the desired thermomechanical effects for specific clinical applications. While Wongchadakul et al. also utilized a similar simulation package to analyze temperature distribution in the skin following laser irradiation across different wavelengths and intensities, our focus diverges significantly.

We value your meticulous observation of the similarities in figures and tables between our study and that of Wongchadakul et al. To address this, we have omitted redundant figures 1 and 2 and table 1 while providing a comprehensive acknowledgment and clear integration of their findings into the revised manuscript.

 

Point 2: The article has numerous references to the  "impact of short-pulse laser radiation" (lines 14, 127, 129,475, 497, 537), although the duration of the laser pulse is not stated. This is an important factor because when femtosecond laser pulses are used, the ablation is characterized by negligible thermal effects on the material due to the very short laser pulse duration contrary to the ablation by several picosecond laser pulses, which imposes limitations on clinical applications.

 

Response 2: We acknowledge the importance of specifying the duration of the laser pulses, particularly in the context of femtosecond laser technology and its impact on thermal effects during ablation. In our research, the utilization of short pulses, particularly in the wavelengths of 532 and 800 nm, indeed encompasses a range of pulse durations from nanoseconds to femtoseconds. The duration of the laser pulse was a critical consideration in our examination, as it influences the extent of thermal effects on the material being irradiated.

While our manuscript does not explicitly state the duration of the laser pulses, we focused on assessing the effect of pulse duration through the duration of the examination. This approach allowed for the adjustment of the number of pulses applied, thereby enabling us to explore the maximization or minimization of the thermomechanical effect within the scope of our study.

 

Point 3: Differences in the laser parameters range: Abstract, line 16: "beam size ranged between 1 and 2 mm". But in Lines 140 & 200: 1-5 mm and Line 259, Table 2. Beam size: 0.5 to 3 mm.

Table 1: Intensity, I (W/mm2) (Epidermis) 1.0, 2.0; Abstract and Line 200:  Intensity 1-2 W/mm2) but in Table 2: I = Intensity (W/mm2) 1-5 (explanation is needed)

 

Response 3: We have carefully addressed these inconsistencies and have taken steps to ensure uniformity and clarity across all sections of the manuscript. Regarding the beam size, we have unified the descriptions throughout the text to reflect a consistent range. Specifically, the beam size ranged between 0.5 and 3 mm, and we have revised Lines 140, 200, and Table 2 to align with this range. Similarly, we have rectified the discrepancies in the intensity values within the abstract and within the text.

 

Point 4: "As Figure (11-a) shows the average effect of the mentioned parameters on (Tmax), the figure shows that the response is not affected by (S and W)."

 

Response 4: We have revised the sentence you mentioned to ensure better comprehension.

 

Reviewer 4 Report

Comments and Suggestions for Authors

The article is interesting and well structured, but can be improved.

Dear authors,

Please note the following comments:

In the abstract, please shortly indicate the main obtained results.

In the last paragraph of the Introduction section, please highlight the novelty of the performed analysis, based on the reported literature review.

The model was meshed using tetrahedral elements. Could you please explain why did you choose this type of element?

You stated that: Mesh convergence analysis has been conducted to determine the optimal number of meshing elements and their sensitivity for reducing the computational cost of simulation scenarios [25, 26]. In this model, the mesh sizes are getting smaller and a convergence shows less than 1% change in the maximal temperature when the total number of mesh elements reaches 22708 elements. It would be useful, for better illustration of the results accuracy, to make a graphical representation to prove the accuracy of the obtained results.

No appropriate model validation was found in the manuscript.

In Figures 4,5, 7,8 and 10, please clearly indicate the units for temperature, von Mises stress and displacement, for better understanding.

Regarding Figure 12 c and d it is hard to understand. You mentioned that ‘The  value of both Tmax and Smax can also be extrapolated as a function of beam intensity (I) and exposure time (T) in Figures (12-c) and (12-d), respectively.’ But in this figures are represented the input variables I and T as a function of responses Tmax and Smax. I think there is an error. Please revise.  

Also, you mentioned ‘Figures (12-c) and (12-d) show the possibility of obtaining minimum values for the skin temperature Tmax and its stress state Smax at low values of beam intensity (I) and exposure time (T)’.  In my opinion, Figures 12 a and b can be used to establish the areas of minimum values for Tmax and Smax.

How you obtained the surface plots for each response? You should indicate the regression equations used and also the corresponding R2 values.

Since there are 2 response variables, it would be beneficial to perform a multi-objective optimization analysis in order to find the best combination of input parameters leading to minimum values of both Tmax and Smax, simultaneolsly.

You mentioned in 3.4 chapter that the optimal parameters were determined in proportion to the minimum values of both temperature Tmax and stress Smax, but you did not indicate exactly these optimal values. Please revise.

In discussion section, comparison with other similar studies must be presented.

Please include in the conclusion section the practical implication of the obtained results.

Conclusions should be rewritten. The conclusions should explain the causes and effects of the phenomena presented in the paper.

Author Response

Dear Respected Reviewer,

Thanks for your insightful comments. 

Point 1: In the abstract, please shortly indicate the main obtained results.

 

We have included a concise summary of the main obtained results in the abstract.

 

Point 2: In the last paragraph of the Introduction section, please highlight the novelty of the performed analysis, based on the reported literature review.

 

Our study stands out for its comprehensive analysis of the impact of short-pulse laser radiation on the heat-affected region within tissues, considering a range of laser variables including wavelength, intensity, beam size, and exposure time.

We implemented a novel approach by constructing a three-layered three-dimensional model within a polar coordinate system using COMSOL Multiphysics. This model integrates the Pennes bioheat transfer model and the Beer-Lambert law, alongside Hooke's law, to accurately simulate the coupled biophysics problem arising from laser-tissue interaction. Our investigation focused on analyzing temperature and stress distributions resulting from laser radiation, providing valuable insights into the thermal and mechanical responses of tissues.

Importantly, our study's novelty lies in its application of Box-Behnken analysis to evaluate the effects of laser parameters on tissue response variables. While our findings indicate that beam size (S) exhibits no significant impact on the response variables, temperature (Tmax) demonstrates sensitivity to both beam intensity (I) and exposure time (T), collectively contributing to 89.6% of observed variation. Additionally, we highlight that while beam size (S) does not significantly affect stress value (Smax), wavelength (W), beam intensity (I), and exposure time (T) collectively account for 71.6% of the observed variation in Smax.

We hope that our developed model, with its qualitative verification against relevant studies, holds promise for optimizing laser treatment parameters tailored to tissues with specific dimensions and properties. Our study contributes to advancing the understanding of laser-tissue interactions and provides a framework for future research and clinical applications in laser therapy.

 

Point 3: The model was meshed using tetrahedral elements. Could you please explain why did you choose this type of element?

 

We chose tetrahedral elements for several reasons. Tetrahedral elements offer advantages in capturing complex geometries and irregular shapes more accurately compared to other element types, such as hexahedral elements. Additionally, tetrahedral meshing tends to be more computationally efficient for models with irregular geometries or regions of high curvature. We have referenced these justifications in our manuscript to provide a comprehensive explanation for the selection of tetrahedral elements in our modeling approach.

Point 4: You stated that: Mesh convergence analysis has been conducted to determine the optimal number of meshing elements and their sensitivity for reducing the computational cost of simulation scenarios [25, 26]. In this model, the mesh sizes are getting smaller, and a convergence shows less than 1% change in the maximal temperature when the total number of mesh elements reaches 22708 elements. It would be useful, for better illustration of the results accuracy, to make a graphical representation to prove the accuracy of the obtained results.

In response to your suggestion, we have added a figure containing the convergence curve of the model in the revised version of the manuscript. This graphical representation serves to illustrate the accuracy of the obtained results more effectively.

 

Point 5: No appropriate model validation was found in the manuscript.

 

We acknowledge the importance of model validation and assure you that our approach includes multiple validation steps. Initially, we employed the model proposed in the study of Wongchadakul et al., which had been previously validated through comparisons of temperature values with experimental studies. Additionally, we conducted thorough comparisons of temperature and stress values to ensure the accuracy of our model's predictions.

Secondly, we expanded the range of studied parameters to enhance our understanding of laser-skin interactions. This broader scope allowed us to capture a more comprehensive picture of the phenomenon and its implications.

Lastly, we adopted the Box-Behnken approach to statistically determine the effect of each parameter. The random runs requested by the design of experiments’ scenario were carefully executed to ensure that no missing values or non-applicable experiments occurred due to out-of-range values.

Point 6: In Figures 4,5, 7,8 and 10, please clearly indicate the units for temperature, von Mises stress and displacement, for better understanding.

We ensured that the units for temperature, von Mises stress, and displacement are clearly indicated in the figures of the revised version to enhance understanding.

Point 7: Regarding Figure 12 c and d it is hard to understand. You mentioned that ‘The value of both Tmax and Smax can also be extrapolated as a function of beam intensity (I) and exposure time (T) in Figures (12-c) and (12-d), respectively.’ But in this figures are represented the input variables I and T as a function of responses Tmax and Smax. I think there is an error. Please revise.

 

Response 7: Thanks for this important mention, we explain that the purpose of Figure (12-c) is only to illustrate the effect of changing the values ​​of laser beam intensity I on both temperature Tmax and stress Smax. Likewise, the purpose of Figure (12-d) is to illustrate the effect the exposure time T varies according to both the temperature Tmax and the stress Smax. The explanation of the aforementioned figures has been reformulated to avoid confusion in understanding the figures.

Figure 12: Box-Behnken optimization results for:

a: Response surface Smax as a function of beam intensity I and exposure time T.

b: Response surface Tmax as a function of beam intensity I and exposure time T.

c: The effect of changing the values ​​of beam intensity I on changing the values ​​of temperature Tmax and stress Smax

d: The effect of changing the values ​​of exposure time T on changing the values ​​of temperature Tmax and stress Smax

 

Point 8: Also, you mentioned ‘Figures (12-c) and (12-d) show the possibility of obtaining minimum values for the skin temperature Tmax and its stress state Smax at low values of beam intensity (I) and exposure time (T)’.  In my opinion, Figures 12 a and b can be used to establish the areas of minimum values for Tmax and Smax.

Response 8: The purpose of showing the response surface is to give a comprehensive view of the behavior of the response (or responses) studied in terms of one of the parameters. That is, the goal of Figures (12-d) and (12-c) is to indicate and prove, not to determine values ​​(as you indicated, it is to determine values ​​from Figures (12-a) and (12-b), this is correct). The explanation under the figure has been modified in the paper.

Point 9: How you obtained the surface plots for each response? You should indicate the regression equations used and also the corresponding R2 values.

Response 9: Equations (11), (12), (13) and (14) are the regression equations as a function of the processing parameters (I, S, T) for predicting the value (Smax)532, (Smax)800, (Tmax)532 and (Tmax)532 respectively.

(Smax)532 = 0.409- 0.059 I- 0.006 S+ 0.00145 T+ 0.0003 I2+ 0.002 S2- 0.000006 T2+ 0.0000 I.S+ 0.000813 I.T      (11)

(Smax)800 = -1.191+ 0.581 I- 0.006 S+ 0.00622 T + 0.0003 I2 + 0.002 S2 - 0.000006 T2 + 0.0000 I.S + 0.000813 I.T   (12)
(Tmax)532 = 28.93+ 3.28 I- 0.18 S+ 0.0760 T+ 0.023 I2+ 0.051 S2- 0.000124 T2+ 0.000 I.S+ 0.01662 I.T           (13)

(Tmax)800 =29.03+ 3.24 I- 0.18 S+ 0.0757 T+ 0.023 I2+ 0.051 S2- 0.000124 T2+ 0.000 I.S+ 0.01662 I.T            (14)

The determination factors are (R-sq)Smax = 93.48%  and (R-sq)Tmax = 97.89%.

 

Point 10: Since there are 2 response variables, it would be beneficial to perform a multi-objective optimization analysis in order to find the best combination of input parameters leading to minimum values of both Tmax and Smax, simultaneously.

Response 10: Thanks for this mention, in fact the selection of parameters was based on the analysis of optimality at the minimum values ​​of Tmax (43 C) and Smax(0.2 Mpa).

Point 11: You mentioned in 3.4 chapter that the optimal parameters were determined in proportion to the minimum values of both temperature Tmax and stress Smax, but you did not indicate exactly these optimal values. Please revise.

Response 11: Rephrase is done, noting that optimal parameters are shown at line 369

The effect of processing parameters (wavelength W, beam size S, laser intensity I, and exposure time T) on temperature and stress distributions was studied in the skin using Box-Behnken design optimization (Table 2). The optimal parameter levels corresponding to the minimum values ​​for each temperature were also determined Tmax (≤ 43 ) and stress Smax ( ≤ 0.2 Mpa)

 

Reviewer 5 Report

Comments and Suggestions for Authors

This paper is devoted to the examination of the photothermal and thermomechanical facts of short-pulse laser irradiation on normal tissues. The paper is well organized and probably contains results that could be interesting for some readers. However, some shortcomings have to be resolved before accepting for publication. 

1) The introduction is too long and has to be shortened by at least 50%. 

2) In Table 1, the authors must cite the reference from which properties were taken, although this reference is mentioned in the text. 

3) I am confused about the equation 10. It is only written without any explanation. I am not sure what equation (10) refers to. 

4) Figures 3-5 are not clear enough. They have to be replotted. 

5) Figures 7, 8, and 10 are also not clear enough. They have to be replotted.

6) The discussion is written in the form of a Conclusion and also is too long. The authors have to rewrite the Discussion to be more specific, and related to their results. 

7) The list of references has to be completed with recent relevant references. 

Author Response

Dear Respected Reviewer,

Thanks for your insightful comments. 

 

Point 1: The introduction is too long and has to be shortened by at least 50%.

 

Response 1: We have taken your suggestion into careful consideration, and in the revised version of the manuscript, we have significantly shortened the introduction by at least 50%. We believe that this modification will improve the clarity and focus of the introduction while still effectively setting the stage for the research presented in the paper.

 

Point 2: In Table 1, the authors must cite the reference from which properties were taken, although this reference is mentioned in the text.

 

Response 2:  We omitted Figures 1 and 2 from the manuscript, as well as Table 1, given that these details are covered comprehensively in a previous study to which we have referred in the introduction and model paragraphs. This streamlining enhances the focus of the current manuscript while maintaining the necessary references and context for readers.

 

Point 3: I am confused about the equation 10. It is only written without any explanation. I am not sure what equation (10) refers to.

 

Response 3:  In the revised version, we have provided a comprehensive explanation of Equation 10 to ensure clarity and understanding for readers. This clarification aims to elucidate the significance and context of the equation within the framework of our research.

 

Points 4 and 5 : Figures 3-5 are not clear enough. They have to be replotted. Figures 7, 8, and 10 are also not clear enough. They have to be replotted.

 

Responses 4 and 5:  We have carefully reviewed your comments and have taken action to address them in the revised version of the manuscript. Specifically, all the mentioned figures have been modified to enhance their quality and clarity.

 

Point 6: The discussion is written in the form of a Conclusion and also is too long. The authors have to rewrite the Discussion to be more specific and related to their results.

 

Response 6:  In response to your comments, we have fully rewritten the discussion in the revised version of the paper. The discussion now focuses more specifically on our results and their implications, aligning closely with the objectives and findings of our study.

We have taken care to ensure that the discussion is concise yet comprehensive, highlighting key insights derived from our research and their relevance to the broader scientific context.

 

Point 7: The list of references has to be completed with recent relevant references.

 

Response 7:  we have expanded and completed our references list by including 9 relevant recent studies that are pertinent to the topic discussed in our manuscript. These additional references serve to enrich the literature review and provide readers with a comprehensive understanding of the current state of research in the field.

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Comment on authors' response to Point 2:

The duration of “short-pulse laser irradiation” must be stated in the manuscript since irradiation with ns, ps, and fs pulse durations produces different thermal and non-thermal effects (e.g., doi: 10.5772/63892; doi.org/10.1515/aot-2021-0044).  

It is therefore suggested that an explanation of the approximation behind using the term "short-pulse laser irradiation" be included in this manuscript.

 

 

Author Response

Response 1: We have addressed the concern regarding the duration of "short-pulse laser irradiation" in our manuscript. Specifically, we have added a dedicated paragraph that clarifies the distinctions between nanosecond (ns), picosecond (ps), and femtosecond (fs) pulse durations, as well as their respective thermal and non-thermal effects. This addition aims to provide a comprehensive understanding of the term "short-pulse laser irradiation" and its implications in our study. Furthermore, we have included citations to the suggested studies (doi: 10.5772/63892; doi.org/10.1515/aot-2021-0044) to support and reinforce the clarification provided in the manuscript. Thank you for highlighting this point, and we believe that our revisions have addressed this concern effectively.

Reviewer 4 Report

Comments and Suggestions for Authors

Dear Editor and authors,

The authors have addressed all my comments and I consider that the paper can be accepted. Thank you.

Author Response

Thanks a lot for your time and effort.

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