title: Prolonged, acute suppression of cysteinyl leukotriene to reduce capsular contracture around silicone implants.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Byung Hwi
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea.
authors.forename: Su Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea. Electronic address: lionheo@gmail.com.
authors.forename: Chan Yeong
authors.initials: CY
authors.lastname: Heo
authors.affiliation: Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 08826, Republic of Korea; Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry; D015289:Leukotrienes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D058628:Myofibroblasts / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012828:Silicones / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D015289:Leukotrienes; D012828:Silicones; D016212:Transforming Growth Factor beta; C112381:cysteinyl-leukotriene; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen; D003545:Cysteine
keywords: Cysteinyl leukotrienes; Fibroblast; Fibrosis; Montelukast; Myofibroblasts; Silicone implants; TGF-β