ABSTRACT: 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. A double-blind randomised-controlled trial. Here, we evaluated application of topical EGCG compared with placebo in 62 healthy human volunteers, over 8 weeks, in scars created in their upper inner arms using skin punch biopsies. RNA sequencing was used here based on 45 samples: day 0 (n=3), week 1 (n=3 placebo, n=3 EGCG), week 2 (n=3 placebo, n=3 EGCG), week 3 (n=3 placebo, n=3 EGCG), week 4 (n=3 placebo, n=3 EGCG), week 5 (n=3 placebo, n=3 EGCG), week 6 (n=3 placebo, n=3 EGCG), week 8 (n=3 placebo, n=3 EGCG). The common differentially expressed genes identified between treated (EGCG) and placebo samples were grouped according to time point (Zonal priming: weeks 1 and 2; Direct application post scar formation (2 weeks post-biopsies): weeks 1, 2, 3, 4, 6). Further exploration of these genes using Gene Ontology and Ingenuity Pathway Analysis revealed gene signatures of relevant biological processes and pathways. Here, RNA sequencing revealed a number of angiogenic, inflammatory and antioxidant genes that were significantly downregulated with EGCG particularly at week 1 including; TPSAB1, VEGFA, EDF, IL17F, IL1A, IL1RL1, IL36A, IL36G, SOD3.