Abstract
The concept of pre-emptive priming of skin pre-surgery offers a novel approach in optimizing cutaneous scarring outcome. We previously showed an anti-scarring topical (epigallocatechin-3-gallate (EGCG)) is effective in improving skin scarring when applied post-surgery. The objective was to deliver an active compound at the optimal time in order to maximize its impact and improve cutaneous scarring. Therefore, pre-emptive application of anti-scarring topical pre-surgery compared with post-surgery can potentially be superior on scarring outcome. This double-blinded randomized placebo-controlled trial compares the effects of pre-emptive priming of skin with an anti-scarring topical pre-surgery versus post-surgery. Healthy volunteers (n = 40) were split into 4-groups; each undergoing different modes of application versus placebo: Group-1 = priming (7Days) pre-injury, Group-2 = priming (3D) pre-injury, Group-3 = immediate (0D) day-of-injury, Group-4 = delayed application (14D) post-injury. Excisional skin-biopsies in upper-arms were evaluated weekly with multiple quantitative devices over 8-weeks. Histological, immunohistochemical, mRNA sequencing and QRT-PCR studies were performed on tissue-biopsies. EGCG reduced mast cells at weeks-4 and 8 by gene and protein analyses (p < 0.01). Group 1 was superior to other groups (p < 0.01) in both clinical (blood flow) and laboratory parameters (elastin and immune marker expression). Additionally, there was down-regulation of angiogenic-markers by mRNA-sequencing and of CD31 and VEGF-A at weeks-4 and 8 (p < 0.01) by immunohistochemistry and at week-4 (p < 0.05) by QRT-PCR. EGCG increased antioxidant levels (HO-1) at week-4 (p < 0.01) plus elastin at week-8 (p < 0.01). In conclusion, pre-emptive priming of skin pre-injury has significant beneficial effects on surgically induced skin scarring shown by reducing mast cells, blood flow and angiogenesis plus increasing elastin content. This clinical trial was registered with ISRCTN (ISRCTN70155584).
Highlights
This double-blind, placebo-controlled clinical trial quantitatively invesThis double-blind,randomized randomized placebo-controlled clinical trial quantitatively tigates the effects of different timings of application of topical anti-scarring formulation investigates the effects of different timings of application of topical anti-scarring (EGCG) versus a placebo in relation to inflammatory response, angiogenesis, antioxidant formulation (EGCG) versus a placebo in relation to inflammatory response, angiogenesis, effects and structural changes in cutaneous skin scarring in healthy human volunteers antioxidant effects and structural changes in cutaneous skin scarring in healthy human (Figure 26)
Our findings demonstrated that EGCG topical application: (1) Mast cell
CKit) number was significantly reduced, (2) Blood flow and angiogenesis (CD31 and and CKit) number was significantly reduced, (2) Blood flow and angiogenesis (CD31 and vascular endothelial growth factor (VEGF)-A expression) were significantly reduced, (3) Antioxidant effect was enhanced by VEGF-A expression) were significantly reduced, (3) Antioxidant effect was enhanced by increased HO-1 levels, (4) Scar thickness was reduced, (5) Viscoelasticity increased and increased HO-1 levels, (4) Scar thickness was reduced, (5) Viscoelasticity increased and elastin expression was significantly increased
Summary
It has inhibited growth and induced shrinkage in keloid scar tissues [26] and reduced inflammatory and fibrotic markers in normal scars ex vivo [27] These observations led us to hypothesize that EGCG may be a potential candidate for use as a topical agent in the treatment of skin scarring in both studies. We postulated that pre-emptive priming with anti-scarring topical to the zone of injury, prior to performing surgically induced excisional punch-biopsies, could further maximize the effects by targeting the source of inflammation earlier. Various modes of anti-scarring topical formulation (EGCG) application were evaluated in this well-established human skin scarring model utilizing a full-thickness excisional surgical biopsy approach to identify whether pre-emptive priming pre-surgically induced injury had a greater impact on scarring outcome compared to day of- or post-injury application. Cal application modalities, study time points and the non-invasive and invasive measures used
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