title: Acute suppression of TGF-ß with local, sustained release of tranilast against the formation of fibrous capsules around silicone implants.
abstract: We propose the acute, local suppression of transforming growth factor beta (TGF-ß), a major profibrotic cytokine, to reduce fibrosis around silicone implants. To this end, we prepared silicone implants that were able to release tranilast, a TGF-ß inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immunohistochemical analyses for 12 weeks after the implantation of the implants in living rats. The capsule thicknesses and collagen densities significantly decreased compared with those around the non-treated silicone implants. Notably, early suppression of TGF-ß affected the fibrogenesis that actually occurs at the late stage of wound healing. This change may be ascribed to the decrease in monocyte recruitment mediated by early TGF-ß during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-ß and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation.
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Subin
authors.initials: S
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, 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 152-742, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Ryul
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea. Electronic address: lionheo@gmail.com.
authors.forename: Chan Yeong
authors.initials: CY
authors.lastname: Heo
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea; Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005355:Fibrosis; D005549:Foreign-Body Reaction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects; D019736:Prostheses and Implants; D017207:Rats, Sprague-Dawley; D012828:Silicones; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D012828:Silicones; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; D003094:Collagen; C012293:tranilast
keywords: Capsular contracture; Fibrosis; Macrophage; Silicone implant; TGF; Tranilast