close
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;18(5):647-656.
doi: 10.1111/iwj.13566. Epub 2021 Mar 17.

Verapamil-containing silicone gel reduces scar hypertrophy

Jangyoun Choi  1 , Yu Na Han  1   2 , Eun Young Rha  3 , Hwi Ju Kang  4 , Ki Joo Kim  1 , Il Kyu Park  4 , Hyun-Jung Kim  5 , Jong Won Rhie  1   2
Affiliations

Verapamil-containing silicone gel reduces scar hypertrophy

Jangyoun Choi et al. Int Wound J. 2021 Oct.

Abstract

A hypertrophic scar is a common dermal fibroproliferative lesion usually treated with topical silicone. Verapamil, a type of calcium channel blocker, is considered a candidate drug for the treatment of hypertrophic scars. Here, we report that the addition of verapamil to topical silicone gel enhances treatment outcomes of hypertrophic scars. Upon creation of hypertrophic scars with the rabbit ear model, varying concentrations of verapamil-added silicone gel (0.1, 1, and 10 mg/g) were applied daily for 28 days. After the animals were euthanised, microscopic measurement was performed for (a) scar elevation index (SEI), (b) fibroblast count, and (c) capillary count. On gross analysis, features of hypertrophic scars were significantly alleviated in the verapamil-added groups. On histologic examination, verapamil-added groups showed (a) reduced SEI (1.93 (1.79-2.67) for control vs 1.34 (1.21-1.51) for silicone only and 1.13 (1.01-1.65) for verapamil-added silicone), (b) fibroblast count 700.5 (599.5-838.5) for control, 613.25 (461-762.5) for silicone only, and 347.33 (182.5-527) for verapamil-added silicone), and (c) capillary formation (52 (35.5-96.5) for control, 46 (28-64.5) for silicone only, and 39.83(24-70) for verapamil-added silicone) (Kruskal-Wallis test, P < .05). On western blot, expression levels of collagen I protein was lower in the 1 mg/g and 10 mg/g verapamil-added silicone compared with control. Therefore, we suggest a therapeutic concentration of verapamil-added silicone gel of at least over 1 mg/g. Further study regarding maximally effective concentration and deeper insight into the mechanism of action should follow.

Keywords: calcium channel blocker; collagen; scar; silicone; verapamil.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

FIGURE 1
FIGURE 1
Study outline. Eight‐millimetre punch wounds were created on each ear of 10 New Zealand rabbits. After 28 days of care, all wounds developed into hypertrophic scars. Scars were evenly distributed into five groups, including a control, and were treated or not with various concentrations of verapamil‐loaded silicone gel. After 4 weeks of treatment, the animals were euthanised and underwent analysis
FIGURE 2
FIGURE 2
Weekly photographs of scars from initial surgery to treatment endpoint. S + VP0.1, silicone plus 0.1 mg/g verapamil. S + VP1, silicone plus 1 mg/g verapamil. S + VP10, silicone plus 10 mg/g verapamil
FIGURE 3
FIGURE 3
Change of scar height among control, silicone only, and verapamil‐added silicone groups. (A). Histology under low‐power field light microscopy (x20). (B). Quantitative measurement of scar elevation index with digital histomorphometry. Asterisks denote statistical significance (P < .05) by the pairwise Dunn test after the Kruskal‐Wallis test. S + VP0.1, silicone plus 0.1 mg/g verapamil. S + VP1, silicone plus 1 mg/g verapamil. S + VP10, silicone plus 10 mg/g verapamil
FIGURE 4
FIGURE 4
Histologic analysis of scar‐related features in verapamil‐added silicone treatment groups. (A) Fibroblast count within a random field of 1 mm2. (B) Tissue cellularity and vascularity from control group to silicone plus verapamil groups in a high‐power field (x400). (C) Number of capillaries within a random field of 1 mm2. Asterisks denote statistical significance (P < .05) by the pairwise Dunn test after the Kruskal‐Wallis test. S + VP0.1, silicone plus 0.1 mg/g verapamil. S + VP1, silicone plus 1 mg/g verapamil. S + VP10, silicone plus 10 mg/g verapamil
FIGURE 5
FIGURE 5
Collagen density and Western blot. (A) Density of collagen in scar area normalised to adjacent normal tissue. (B) Western blot of COL1 and MMP‐1 for each group. Asterisks denote statistical significance (P < .05) by pairwise Dunn test after Kruskal‐Wallis test. S + VP0.1, silicone plus 0.1 mg/g verapamil. S + VP1, silicone plus 1 mg/g verapamil. S + VP10, silicone plus 10 mg/g verapamil
See this image and copyright information in PMC

References

    1. Kloeters O, Tandara A, Mustoe TA. Hypertrophic scar model in the rabbit ear: a reproducible model for studying scar tissue behavior with new observations on silicone gel sheeting for scar reduction. Wound Repair Regen. 2007;15(Suppl 1):S40‐S45. - PubMed
    1. Morris DE, Wu L, Zhao LL, et al. Acute and chronic animal models for excessive dermal scarring: quantitative studies. Plast Reconstr Surg. 1997;100(3):674‐681. - PubMed
    1. Perez JL, Rohrich RJ. Optimizing postsurgical scars: a systematic review on best practices in preventative scar management. Plast Reconstr Surg. 2017;140(6):782e‐793e. - PubMed
    1. Ahn ST, Monafo WW, Mustoe TA. Topical silicone gel: a new treatment for hypertrophic scars. Surgery. 1989;106(4):781‐786.discussion 6‐7. - PubMed
    1. Saulis AS, Chao JD, Telser A, Mogford JE, Mustoe TA. Silicone occlusive treatment of hypertrophic scar in the rabbit model. Aesthetic Surg J. 2002;22(2):147‐153. - PubMed

LinkOut - more resources