Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial
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 a...
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MDPI AG
2021-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/510 |
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| author | Sara Ud-Din Traci A. Wilgus Douglas D. McGeorge Ardeshir Bayat |
| author_facet | Sara Ud-Din Traci A. Wilgus Douglas D. McGeorge Ardeshir Bayat |
| author_sort | Sara Ud-Din |
| collection | DOAJ |
| description | 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 (<i>n</i> = 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 (<i>p</i> < 0.01). Group 1 was superior to other groups (<i>p</i> < 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 (<i>p</i> < 0.01) by immunohistochemistry and at week-4 (<i>p</i> < 0.05) by QRT-PCR. EGCG increased antioxidant levels (HO-1) at week-4 (<i>p</i> < 0.01) plus elastin at week-8 (<i>p</i> < 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). |
| first_indexed | 2024-03-10T12:30:33Z |
| format | Article |
| id | doaj.art-0e7350198c03453a861e1228a015b1e0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:30:33Z |
| publishDate | 2021-04-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-0e7350198c03453a861e1228a015b1e02023-11-21T14:40:53ZengMDPI AGPharmaceutics1999-49232021-04-0113451010.3390/pharmaceutics13040510Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical TrialSara Ud-Din0Traci A. Wilgus1Douglas D. McGeorge2Ardeshir Bayat3Plastic and Reconstructive Surgery Research, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M13 9PT, UKDepartment of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH 43210, USAGrosvenor Nuffield Hospital, Chester CH4 7QP, UKPlastic and Reconstructive Surgery Research, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M13 9PT, UKThe 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 (<i>n</i> = 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 (<i>p</i> < 0.01). Group 1 was superior to other groups (<i>p</i> < 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 (<i>p</i> < 0.01) by immunohistochemistry and at week-4 (<i>p</i> < 0.05) by QRT-PCR. EGCG increased antioxidant levels (HO-1) at week-4 (<i>p</i> < 0.01) plus elastin at week-8 (<i>p</i> < 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).https://www.mdpi.com/1999-4923/13/4/510pre-emptive skin primingzonal therapyhuman skincutaneous scarringtopical treatmentsurgical wounds |
| spellingShingle | Sara Ud-Din Traci A. Wilgus Douglas D. McGeorge Ardeshir Bayat Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial Pharmaceutics pre-emptive skin priming zonal therapy human skin cutaneous scarring topical treatment surgical wounds |
| title | Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial |
| title_full | Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial |
| title_fullStr | Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial |
| title_full_unstemmed | Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial |
| title_short | Pre-Emptive Priming of Human Skin Improves Cutaneous Scarring and Is Superior to Immediate and Delayed Topical Anti-Scarring Treatment Post-Wounding: A Double-Blind Randomised Placebo-Controlled Clinical Trial |
| title_sort | pre emptive priming of human skin improves cutaneous scarring and is superior to immediate and delayed topical anti scarring treatment post wounding a double blind randomised placebo controlled clinical trial |
| topic | pre-emptive skin priming zonal therapy human skin cutaneous scarring topical treatment surgical wounds |
| url | https://www.mdpi.com/1999-4923/13/4/510 |
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