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.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
17
04
2023
accepted:
22
08
2023
medline:
11
9
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
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. 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. 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. ClinicalTrials.gov: NCT04736251.
Sections du résumé
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.
Identifiants
pubmed: 37682920
doi: 10.1371/journal.pone.0285230
pii: PONE-D-23-08823
pmc: PMC10490849
doi:
Substances chimiques
Carbon Dioxide
142M471B3J
Banques de données
ClinicalTrials.gov
['NCT04736251']
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0285230Informations de copyright
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.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Semin Plast Surg. 2012 Aug;26(3):125-30
pubmed: 23904820
Burns. 2015 Mar;41(2):252-6
pubmed: 25468478
Stat Med. 1995 Sep 15;14(17):1933-40
pubmed: 8532986
Nat Rev Dis Primers. 2020 Feb 13;6(1):11
pubmed: 32054846
Mol Med. 2011 Jan-Feb;17(1-2):113-25
pubmed: 20927486
Arch Plast Surg. 2014 Nov;41(6):620-9
pubmed: 25396172
Ann Plast Surg. 2014;72(6):S198-201
pubmed: 24835874
Arch Facial Plast Surg. 2008 Mar-Apr;10(2):93-102
pubmed: 18347236
Burns. 2019 Sep;45(6):1311-1324
pubmed: 31327551
Plast Reconstr Surg. 1998 Nov;102(6):2190-5
pubmed: 9811021
Semin Plast Surg. 2012 Aug;26(3):109-16
pubmed: 23904818
Clin Cosmet Investig Dermatol. 2014 Nov 06;7:301-11
pubmed: 25395868
Dev Cell. 2014 Dec 22;31(6):722-33
pubmed: 25499914
Am Fam Physician. 2009 Aug 1;80(3):253-60
pubmed: 19621835
BMJ Open. 2020 Apr 8;10(4):e035345
pubmed: 32273318
Burns. 2003 May;29(3):207-13
pubmed: 12706612
J Invest Dermatol. 2019 Dec;139(12):2425-2436.e5
pubmed: 31220456
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Circ Res. 2017 May 12;120(10):1632-1648
pubmed: 28495994
Nat Med. 2022 Jan;28(1):18-20
pubmed: 35039659
JAMA. 1982 Jan 1;247(1):29
pubmed: 7053437
Br J Dermatol. 2018 Dec;179(6):1307-1314
pubmed: 30101519
J Invest Dermatol. 2018 Apr;138(4):802-810
pubmed: 29080679
J Res Med Sci. 2011 Sep;16(9):1189-95
pubmed: 22973388
BMJ. 2013 Jan 08;346:e7586
pubmed: 23303884
Clin Plast Surg. 2017 Oct;44(4):767-779
pubmed: 28888302
Burns Trauma. 2019 Jan 29;7:1
pubmed: 30723753
Lancet. 2016 Oct 1;388(10052):1427-1436
pubmed: 27707499
Lasers Surg Med. 2004;34(5):426-38
pubmed: 15216537
Med Care. 2019 May;57 Suppl 5 Suppl 1:S18-S23
pubmed: 30985592
Burns Trauma. 2016 Apr 27;4:14
pubmed: 27574684
Arch Dermatol. 1999 Apr;135(4):444-54
pubmed: 10206052