Novel strategies using montelukast to suppress fibrosis around silicone implants

Abstract

Implantable silicon medical devices have evolved in various forms depending on their use. However, there are limitations to their use due to side effects that occur after in vivo transplantation. Among implantable silicone medical devices, many side effects have been reported in silicone breast implants. A typical side effect is the occurrence of capsular contracture, which is mediated by an in vivo immune response. In severe cases, capsular contracture may require secondary surgery and is associated with pain and abnormal breast shape. Thus, it is important to understand the side effects that may occur when inserting silicone breast implants and to identify potential measures to suppress the side effects associated with fibrosis.<br/> In this study, I investigated the fibrogenesis associated with in vivo implants and inhibited fibrosis by controlling drug delivery. By analyzing the morphogenesis of macrophages, the overall process associated with the fibrosis-inhibition mechanism was verified. In addition, an implant with effective fibrosis-inhibiting properties was developed through the introduction of a new drug called montelukast, and its efficacy was verified. To verify the tissue factors involved in the fibrosis reaction steps, a shell of a silicone implant 2 cm in diameter was prepared. After drug loading, the shell was bonded using a medical bonding agent so that the surface was exposed on both sides. Four different groups of samples (SI, PLGA_SI, MON_SI and PLGA_MON_SI) were prepared and implanted into a subcutaneous pocket in 8-week-old Sprague-Dawley rats. Biopsies were performed at five predetermined periods (1, 2, 4, 8, and 12 weeks) to verify suppression of the fibrosis pathway. Fibrosis- and inflammation-related factors, specifically, macrophages, fibroblasts, transforming growth factor-β (TGF-β), myofibroblasts, collagen density and capsule thickness were investigated. In the case of inflammatory factors, the expression pattern was high in the SI and PLGA_SI groups