SMOOTH protocol:  A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring

Yung-Yi Chen; Krupali M Patel; Rizwana Imran; Tarek Hassouna; Ezekwe Amirize; Abdulrazak Abdulsalam; Jonathan Bishop; Anita Slade; Maximina Ventura; Jeremy Yarrow; Janet M Lord; Yvonne Wilson; Naiem S Moiemen

doi:10.1371/journal.pone.0285230

SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring

Yung-Yi Chen^*, Krupali M Patel, Rizwana Imran, Tarek Hassouna, Ezekwe Amirize, Abdulrazak Abdulsalam, Jonathan Bishop, Anita Slade, Maximina Ventura, Jeremy Yarrow, Janet M Lord, Yvonne Wilson, Naiem S Moiemen

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells.

Methods: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy.

Discussion: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS.

Trial registration: ClinicalTrials.gov: NCT04736251.

Original language	English
Article number	e0285230
Number of pages	8
Journal	PLoS ONE
Volume	18
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0285230
Publication status	Published - 8 Sept 2023

Bibliographical note

Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

Humans
Pilot Projects
Lasers, Gas/therapeutic use
Prospective Studies
Cicatrix, Hypertrophic/radiotherapy
Low-Level Light Therapy
Carbon Dioxide
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
Observational Studies as Topic

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Chen, Y.-Y., Patel, K. M., Imran, R., Hassouna, T., Amirize, E., Abdulsalam, A., Bishop, J., Slade, A., Ventura, M., Yarrow, J., Lord, J. M., Wilson, Y., & Moiemen, N. S. (2023). SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring. PLoS ONE, 18(9), Article e0285230. https://doi.org/10.1371/journal.pone.0285230

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title = "SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring",

abstract = "Background: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. Methods: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan{\textregistered} Cortex, Cutometer{\textregistered} and ColoriMeter{\textregistered}DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. Discussion: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. Trial registration: ClinicalTrials.gov: NCT04736251.",

keywords = "Humans, Pilot Projects, Lasers, Gas/therapeutic use, Prospective Studies, Cicatrix, Hypertrophic/radiotherapy, Low-Level Light Therapy, Carbon Dioxide, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Observational Studies as Topic",

author = "Yung-Yi Chen and Patel, {Krupali M} and Rizwana Imran and Tarek Hassouna and Ezekwe Amirize and Abdulrazak Abdulsalam and Jonathan Bishop and Anita Slade and Maximina Ventura and Jeremy Yarrow and Lord, {Janet M} and Yvonne Wilson and Moiemen, {Naiem S}",

note = "Copyright: {\textcopyright} 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2023",

month = sep,

day = "8",

doi = "10.1371/journal.pone.0285230",

language = "English",

volume = "18",

journal = "PLoS ONE",

issn = "1932-6203",

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Chen, Y-Y, Patel, KM, Imran, R, Hassouna, T, Amirize, E, Abdulsalam, A, Bishop, J, Slade, A, Ventura, M, Yarrow, J, Lord, JM, Wilson, Y & Moiemen, NS 2023, 'SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring', PLoS ONE, vol. 18, no. 9, e0285230. https://doi.org/10.1371/journal.pone.0285230

SMOOTH protocol: A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring. / Chen, Yung-Yi; Patel, Krupali M; Imran, Rizwana et al.
In: PLoS ONE, Vol. 18, No. 9, e0285230, 08.09.2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - SMOOTH protocol

T2 - A pilot randomised prospective intra-patient single-blinded observational study for examining the mechanistic basis of ablative fractional carbon dioxide laser therapy in treating hypertrophic scarring

AU - Chen, Yung-Yi

AU - Patel, Krupali M

AU - Imran, Rizwana

AU - Hassouna, Tarek

AU - Amirize, Ezekwe

AU - Abdulsalam, Abdulrazak

AU - Bishop, Jonathan

AU - Slade, Anita

AU - Ventura, Maximina

AU - Yarrow, Jeremy

AU - Lord, Janet M

AU - Wilson, Yvonne

AU - Moiemen, Naiem S

N1 - Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2023/9/8

Y1 - 2023/9/8

N2 - Background: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. Methods: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. Discussion: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. Trial registration: ClinicalTrials.gov: NCT04736251.

AB - Background: Burn injuries are the fourth most common type of trauma and are associated with substantial morbidity and mortality. The impact of burn injury is clinically significant as burn injuries often give rise to exuberant scarring. Hypertrophic scarring (HTS) is a particular concern as up to 70% of burns patients develop HTS. Laser therapy is used for treating HTS and has shown positive clinical outcomes, although the mechanisms remain unclear limiting approaches to improve its effectiveness. Emerging evidence has shown that fibroblasts and senescent cells are important modifiers of scarring. This study aims to investigate the cellular kinetics in HTS after laser therapy, with a focus on the association of scar reduction with the presence of senescent cells. Methods: We will conduct a multicentre, intra-patient, single-blinded, randomised controlled longitudinal pilot study with parallel assignments to achieve this objective. 60 participants will be recruited to receive 3 interventional ablative fractional CO2 laser treatments over a 12-month period. Each participant will have two scars randomly allocated to receive either laser treatment or standard care. Biopsies will be obtained from laser-treated, scarred-no treatment and non-scarred tissues for immune-histological staining to investigate the longitudinal kinetics of p16INK4A+-senescent cells and fibroblast subpopulations (CD90+/Thy1+ and αSMA+). Combined subjective scar assessments including Modified Vancouver Scar Scale, Patient and Observer Scar Assessment Scale and Brisbane Burn Scar Impact Profile; and objective assessment tools including 3D-Vectra-H1 photography, DermaScan® Cortex, Cutometer® and ColoriMeter®DSMIII will be used to evaluate clinical outcomes. These will then be used to investigate the association between senescent cells and scar reduction after laser therapy. This study will also collect blood samples to explore the systemic biomarkers associated with the response to laser therapy. Discussion: This study will provide an improved understanding of mechanisms potentially mediating scar reduction with laser treatment, which will enable better designs of laser treatment regimens for those living with HTS. Trial registration: ClinicalTrials.gov: NCT04736251.

KW - Humans

KW - Pilot Projects

KW - Lasers, Gas/therapeutic use

KW - Prospective Studies

KW - Cicatrix, Hypertrophic/radiotherapy

KW - Low-Level Light Therapy

KW - Carbon Dioxide

KW - Randomized Controlled Trials as Topic

KW - Multicenter Studies as Topic

KW - Observational Studies as Topic

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DO - 10.1371/journal.pone.0285230

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SN - 1932-6203

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JO - PLoS ONE

JF - PLoS ONE

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