Prolonged, acute suppression of cysteinyl leukotriene to reduce capsular contracture around silicone implants

[Display omitted] We hypothesize that periodically early, local suppression of cysteinyl leukotrienes (CysLTs), which are potent inflammatory mediators, can reduce the fibrotic capsular contracture around silicone implants. We tested this hypothesis with the silicone implants enabled with the sustai...

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Bibliographic Details
Published in:Acta biomaterialia 2017-03, Vol.51, p.209-219
Main Authors: Kim, Byung Hwi, Park, Min, Park, Hyo Jin, Lee, Seung Ho, Choi, Sung Yoon, Park, Chun Gwon, Han, Su Min, Heo, Chan Yeong, Choy, Young Bin
Format: Article
Language:English
Subjects:
Adipose Tissue - physiology
Animal tissues
Animals
Collagen
Collagen - metabolism
Controlled release
Cysteine - metabolism
Cysteinyl leukotrienes
Cystic fibrosis
Female
Fibroblast
Fibroblasts
Fibroblasts - metabolism
Fibrosis
Implants
Implants, Experimental
Inflammation
Inflammation - pathology
Lactic Acid - chemistry
Leukocytes
Leukocytes (polymorphonuclear)
Leukotrienes
Leukotrienes - metabolism
Macrophages - metabolism
Microscopy, Electron, Scanning
Montelukast
Myofibroblasts
Myofibroblasts - metabolism
Polyglycolic Acid - chemistry
Rats
Rats, Sprague-Dawley
Silicone implants
Silicones
Silicones - chemistry
Stiffness
Studies
Sustained release
TGF-β
Tissue engineering
Transforming growth factor
Transforming Growth Factor beta - metabolism
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Summary:[Display omitted] We hypothesize that periodically early, local suppression of cysteinyl leukotrienes (CysLTs), which are potent inflammatory mediators, can reduce the fibrotic capsular contracture around silicone implants. We tested this hypothesis with the silicone implants enabled with the sustained release of montelukast, a CysLT receptor antagonist, for 3 and 15days. In this work, we inserted each of the distinct implants into the pocket of the subpanniculus carnosus plane of living rats and performed histological and immunofluorescent (IF) analyses of the tissues biopsied at predetermined periods for 12weeks after implant insertion. The implants with montelukast exhibited significantly reduced polymorphonuclear leukocytes (i.e., PMNs), implying a concurrent reduction of CysLT. This effect was more prominent after long-term local montelukast exposure. Thus, fewer fibroblasts were recruited, thereby reducing transforming growth factor (TGF)-β and myofibroblasts in the tissue around the implant. Therefore, the fibrotic capsule formation, which was assessed using the capsule thickness and collagen density, decreased along with the myofibroblasts. Additionally, the tissue biopsied at the experimental end point exhibited significantly decreased mechanical stiffness. Capsular contracture is troublesome, making the tissues hardened around the silicone implant. This causes serious pain and discomfort to the patients, often leading to secondary surgery for implant replacement. To resolve this, we suggest a strategy of long-term, local suppression of cysteinyl leukotriene, an important mediator present during inflammation. For this, we propose a silicone implant abled to release a drug, montelukast, in a sustained manner. We tested our drug-release implant in living animals, which exhibited a significant decrease in capsule formation compared with the intact silicone implant. Therefore, we conclude that the sustained release of montelukast at the local insertion site represents a promising way to reduce capsular contracture around silicone implants.
ISSN:1742-7061
1878-7568
DOI:10.1016/j.actbio.2017.01.033