TY - JOUR
T1 - Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model
AU - Jia, Shengxian
AU - Xie, Ping
AU - Hong, Seok J.
AU - Galiano, Robert D.
AU - Mustoe, Thomas A.
N1 - Funding Information:
Disclosure: Supported by the Armed Forces Institute of Regenerative Medicine (AFIRM), contract number W81X-WH-13-2-0054 from the U.S. Army Medical Research and Material Command (USAMRMC). The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Background: We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model. Methods: Twenty New Zealand White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14-25. Four or 6 full-Thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring. Results: Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium-and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium-and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1. Conclusions: Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.
AB - Background: We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model. Methods: Twenty New Zealand White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14-25. Four or 6 full-Thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring. Results: Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium-and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium-and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1. Conclusions: Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.
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U2 - 10.1097/GOX.0000000000001294
DO - 10.1097/GOX.0000000000001294
M3 - Article
C2 - 28740761
AN - SCOPUS:85032348814
SN - 2169-7574
VL - 5
JO - Plastic and Reconstructive Surgery - Global Open
JF - Plastic and Reconstructive Surgery - Global Open
IS - 6
M1 - e1294
ER -