A double-blind randomized trial demonstrates the role of zonal priming & direct topical application of epigallocatechin-3-gallate in modulation of cutaneous scarring in human skin

Abstract Background Epigallocatechin-3-gallate (EGCG), a polyphenol, influences cutaneous wound healing due to its anti-angiogenic, anti-inflammatory and anti-oxidant properties. We previously demonstrated 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 immediate treatment of zone-of-injury at the time of wounding prior to scar formation. Trial Design A double-blind randomised-controlled trial. Methods We assessed EGCG application compared to placebo over 1-6 weeks , in scars created in 62 human volunteers using quantitative non-invasive devices, immunohistochemical analysis, mRNA sequencing and QRT-PCR of tissue-biopsies. Results EGCG reduced mast cells at weeks 1-3 evidenced by gene and protein analyses (p≤0.01). M2 macrophages were increased with EGCG compared to placebo. EGCG application by zonal-priming significantly downregulated VEGFA and CD31 at week 1 and 2-4 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 non-invasively and by increased hyaluronic acid (p Conclusions We demonstrate the beneficial role of both zonal priming and direct EGCG application in scar therapy with positive effect on scar thickness, erythema, hydration and elasticity.