Covalently Grafted 2-Methacryloyloxyethyl Phosphorylcholine Networks Inhibit Fibrous Capsule Formation around Silicone Breast Implants in a Porcine Model

Abstract

The surface of human silicone breast implants is covalently grafted at a high density with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. Addition of crosslinkers is essential for enhancing the density and mechanical durability of the MPC graft. The MPC graft strongly inhibits not only adsorption but also the conformational deformation of fibrinogen, resulting in the exposure of a buried amino acid sequence, gamma 377-395, which is recognized by inflammatory cells. Furthermore, the numbers of adhered macrophages and the amounts of released cytokines (MIP-1 alpha, MIP-1 beta, IL-8, TNF alpha, IL-1 alpha, IL-1 beta, and IL-10) are dramatically decreased when the MPC network is introduced at a high density on the silicone surface (cross-linked PMPC-silicone). We insert the MPC-grafted human silicone breast implants into Yorkshire pigs to analyze the in vivo effect of the MPC graft on the capsular formation around the implants. After 6 month implantation, marked reductions of inflammatory cell recruitment, inflammatory-related proteins (TGF-beta and myeloperoxidase), a myoblast marker (alpha-smooth muscle actin), vascularity-related factors (blood vessels and VEGF), and, most importantly, capsular thickness are observed on the crosslinked PMPC-silicone. We propose a mechanism of the MPC grafting effect on fibrous capsular formation around silicone implants on the basis of the in vitro and in vivo results.