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, γ377−395, which is recognized by inflammatory cells. Furthermore, the numbers of adhered macrophages and the amounts of released cytokines (MIP-1α, MIP-1β, IL-8, TNFα, IL-1α, IL-1β, 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-β and myeloperoxidase), a myoblast marker (α-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.

Ahmed implant coated with poly(2-methacryloyloxyethyl phosphorylcholine) inhibits foreign body reactions in rabbit eyes

“…In previous studies, the use of PMPC-coated hydrophilic surfaces dramatically reduced the adsorption of proteins and fibrinogens [ 17 , 40 ]. Moreover, clinical applications of PMPC in silicone implants showed that they exhibit high biocompatibility as they induce lower levels of fibrous capsular formation and also inhibit the expression of inflammatory markers, such as myeloperoxidase, TGF-β, and α-smooth muscle actin, in surrounding tissues by 20%–30% compared to non-grafted implants [ 17 , 47 ]. The present study also showed that the AGVs wPMPC suppress fibrosis in the conjunctiva by reducing the number of inflammatory cells and the fibrous capsular thickness.…”

Recent progress and perspectives in applications of 2-methacryloyloxyethyl phosphorylcholine polymers in biodevices at small scales

“…PDMS is a common material of breast silicone that is initiated before covalent bonding with PMPC via photo-or heat-induced radical polymerization. [88][89][90][91] Ham et al grafted a nanolayer of PMPC on PDMS silicone by simply dipping the silicone in a mixture of MPC and ethylene glycol dimethacrylate, and irradiating the silicone with UV light. The covalently grafted PMPC silicone was implanted in a Yorkshire pig for 6 months and showed excellent anti-inflammation and anti-fibrous capsule behavior, as displayed in Fig.…”

“…4B. 90 Kang et al introduced heat-induced polymerization as an alternative to UV-induced polymerization. 91 They immersed a silicone breast in an initiator mixture solution of benzoyl peroxide and dipentaerythritol penta-/ hexa-acrylate in dichloromethane/acetone for 16 h at 70 1C.…”

In situ Tissue Regeneration in the Cornea from Bench to Bedside

“…Therefore, for subsequent use in patients diagnosed with severe pathologies associated with high graft rejection risk, 2-methacryloyloxyethyl phosphorylcholine (MPC) was incorporated into the RHCIII implants as interpenetrating networks [Islam et al, 2018]. MPC has been shown to have inflammation suppressing properties [Yumoto et al, 2015], which may be due to its anti-fouling properties that includes preventing the adhesion of inflammatory cells such as macrophages [Ham et al, 2020]. The resulting RHCIII-MPC implants were able to promote stable regeneration in high-risk corneas with ulcers and scarring over the observation period of an average of 2 years [Islam et al, 2018].…”