Montelukast Attenuates Retraction of Expanded Flap by Inhibiting Capsule Formation around Silicone Expander through TGF-β1 Signaling

Abstract

Background: Tissue expansion has tremendous applications in plastic surgery, but flap retraction provides insufficient tissue for use. Inspired by the use of montelukast to suppress capsular contracture, the authors investigated the effects of montelukast on capsule formation around the expander and retraction of the expanded scalp of the rat. Methods: Thirty-six male Sprague-Dawley rats were randomly divided into control and montelukast groups. In each group, 12 expanded flaps with or without capsules were harvested for histologic and molecular analysis; the six remaining expanded flaps were transferred to repair defects. Myofibroblast and transforming growth factor-β1 expression in the capsule was determined using immunofluorescence. Capsule ultrastructure was observed using transmission electron microscopy. Related protein expression in the capsules was detected using Western blot analysis. Results: A comparison of control and montelukast groups revealed that areas of the harvested expanded flaps with capsules were greater (2.04 ± 0.11 cm2 versus 2.42 ± 0.12 cm2, respectively; P = 0.04); the retraction rate decreased (41.3% ± 2.16% versus 28.13% ± 2.17%, respectively; P < 0.01). However, the increased areas and decreased retraction disappeared after capsule removal. The number of myofibroblasts declined. Thin, sparse collagen fibers were observed in the capsules. The expression of COL1, COL3, TGF-β1, EGR1, and phosphorylated ERK1/2 in the capsules decreased. Furthermore, the recipient area repaired by the transferred expanded flap was increased from 4.25 ± 0.39 cm2 to 6.58 ± 0.31 cm2 (P < 0.01). Conclusion: Montelukast attenuates retraction of the expanded flap by inhibiting capsule formation through suppressing transforming growth factor-β1 signaling. Clinical Relevance Statement: This study provides novel insights into a method for increasing the area of the expanded flap.