Sara Ud-Din1, Philip Foden2, Mohsin Mazhari3, Samer Al-Habba3, Mohamed Baguneid4, Silvia Bulfone-Paus5, Douglas McGeorge6, Ardeshir Bayat7. 1. Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK. 2. Medical Statistics, Manchester University Foundation Trust, Manchester, UK. 3. Adult Histopathology, Manchester University Foundation Trust, Manchester, UK. 4. Vascular Surgery, Manchester University Foundation Trust, Manchester, UK. 5. Faculty of Biology, Medicine and Health, Centre for Dermatology Research, University of Manchester, Manchester, UK. 6. Grosvenor Nuffield Hospital, Chester, UK. 7. Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK. Electronic address: ardeshir.bayat@manchester.ac.uk.
Abstract
BACKGROUND:Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing because of its antiangiogenic, anti-inflammatory, and antioxidant properties. We previously showed the role of EGCG in scarring in ex vivo human scar models. Here, we evaluate direct application of topical EGCG compared with zonal priming, a unique concept in the immediate treatment of the zone of injury at the time of wounding before scar formation. TRIAL DESIGN: Double-blind randomized controlled trial. METHODS: We assessed EGCG application compared with placebo over 1-6 weeks in scars created in 62 human volunteers using quantitative noninvasive devices, immunohistochemical analysis, mRNA sequencing, and quantitative real-time reverse transcriptase-PCR of tissue biopsy samples. RESULTS:EGCG reduced mast cells at weeks 1-3, as evidenced by gene and protein analyses (P ≤ 0.01). M2 macrophages were increased with EGCG compared with placebo. EGCG application by zonal priming significantly down-regulated VEGFA and CD31 at week 1 and at 1-2 weeks after direct application (P ≤ 0.01). Direct EGCG application also reduced scar thickness at weeks 1-3 (P = 0.001) and increased scar elasticity at week 4 (P = 0.01). Increased hydration was evident both noninvasively and by increased hyaluronic acid levels (P < 0.01) at week 3. CONCLUSIONS: We show the beneficial role of both zonal priming and direct EGCG application in scar therapy with positive effects on scar thickness, erythema, hydration, and elasticity. Trial register: International standard randomized controlled trial, registration number ISRCTN 18643079; July 16, 2018.
RCT Entities:
BACKGROUND:Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing because of its antiangiogenic, anti-inflammatory, and antioxidant properties. We previously showed the role of EGCG in scarring in ex vivo human scar models. Here, we evaluate direct application of topical EGCG compared with zonal priming, a unique concept in the immediate treatment of the zone of injury at the time of wounding before scar formation. TRIAL DESIGN: Double-blind randomized controlled trial. METHODS: We assessed EGCG application compared with placebo over 1-6 weeks in scars created in 62 human volunteers using quantitative noninvasive devices, immunohistochemical analysis, mRNA sequencing, and quantitative real-time reverse transcriptase-PCR of tissue biopsy samples. RESULTS:EGCG reduced mast cells at weeks 1-3, as evidenced by gene and protein analyses (P ≤ 0.01). M2 macrophages were increased with EGCG compared with placebo. EGCG application by zonal priming significantly down-regulated VEGFA and CD31 at week 1 and at 1-2 weeks after direct application (P ≤ 0.01). Direct EGCG application also reduced scar thickness at weeks 1-3 (P = 0.001) and increased scar elasticity at week 4 (P = 0.01). Increased hydration was evident both noninvasively and by increased hyaluronic acid levels (P < 0.01) at week 3. CONCLUSIONS: We show the beneficial role of both zonal priming and direct EGCG application in scar therapy with positive effects on scar thickness, erythema, hydration, and elasticity. Trial register: International standard randomized controlled trial, registration number ISRCTN 18643079; July 16, 2018.
Authors: Fellipe D Felin; Ednea A Maia-Ribeiro; Carollina D Felin; Nathália A C Bonotto; Bárbara O Turra; Isabel Roggia; Verônica F Azzolin; Cibele F Teixeira; Moisés H Mastella; Carolina Rodrigues de Freitas; Jaqueline Greijanim; Daniel Santos; Erico M M Flores; Fernanda Barbisan; Ivana B M Cruz; Tiango A Ribeiro Journal: Oxid Med Cell Longev Date: 2022-06-26 Impact factor: 7.310