A Double-Blind, Randomized Trial Shows the Role of Zonal Priming and Direct Topical Application of Epigallocatechin-3-Gallate in the Modulation of Cutaneous Scarring in Human Skin

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.