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

We propose the acute, local suppression of transforming growth factor beta (TGF-beta), 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-beta inhibitor, in a sustained manner for 5 days or 15 days. We performed histologic and immuno-histochemical analyses for 12weeks 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-beta 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-beta during the acute inflammatory reaction. Thus, a significant decrease in differentiated macrophages was observed along with a decrease in the quantity of TGF-beta and fibroblasts during the subsequent inflammation stage; these changes led to a diminished fibrotic capsule formation. (C) 2014 Elsevier B.V. All rights reserved.