Acute suppression of TGF-ß with local, sustained release of tranilast against the formation of fibrous capsules around silicone implants

J Control Release. 2015 Feb 28:200:125-37. doi: 10.1016/j.jconrel.2014.12.021. Epub 2014 Dec 18.

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.

Keywords: Capsular contracture; Fibrosis; Macrophage; Silicone implant; TGF; Tranilast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cell Count
  • Cell Proliferation / drug effects
  • Collagen / metabolism
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / therapeutic use
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibrosis
  • Foreign-Body Reaction / drug therapy*
  • Foreign-Body Reaction / metabolism
  • Foreign-Body Reaction / pathology
  • Macrophages / drug effects
  • Male
  • Monocytes / drug effects
  • Prostheses and Implants*
  • Rats, Sprague-Dawley
  • Silicones
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • ortho-Aminobenzoates / administration & dosage*
  • ortho-Aminobenzoates / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Silicones
  • Transforming Growth Factor beta
  • ortho-Aminobenzoates
  • Collagen
  • tranilast