Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
Hyun-Seok Kim,
Seongsoo Kim,
Byung-Ho Shin,
Chan-Yeong Heo,
Omar Faruq,
Le Thi Van Anh,
Nilsu Dönmez,
Pham Ngoc Chien,
Dong-Sik Shin,
Sun-Young Nam,
Rong-Min Baek
Affiliations
Hyun-Seok Kim
Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea
Seongsoo Kim
Division of Chemical and Bioengineering, Kangwon National University, Chuncheon 24341, Korea
Byung-Ho Shin
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Chan-Yeong Heo
Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea
Omar Faruq
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Le Thi Van Anh
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Nilsu Dönmez
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Pham Ngoc Chien
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Dong-Sik Shin
Department of Chemical and Biological Engineering, Sookmyung Women’s University, Seoul 04310, Korea
Sun-Young Nam
Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Rong-Min Baek
Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea
Breast augmentations with silicone implants can have adverse effects on tissues that, in turn, lead to capsular contracture (CC). One of the potential ways of overcoming CC is to control the implant/host interaction using immunomodulatory agents. Recently, a high ratio of anti-inflammatory (M2) macrophages to pro-inflammatory (M1) macrophages has been reported to be an effective tissue regeneration approach at the implant site. In this study, a biofunctionalized implant was coated with interleukin (IL)-4 to inhibit an adverse immune reaction and promoted tissue regeneration by promoting polarization of macrophages into the M2 pro-healing phenotype in the long term. Surface wettability, nitrogen content, and atomic force microscopy data clearly showed the successful immobilization of IL-4 on the silicone implant. Furthermore, in vitro results revealed that IL-4-coated implants were able to decrease the secretion of inflammatory cytokines (IL-6 and tumor necrosis factor-α) and induced the production of IL-10 and the upregulation of arginase-1 (mannose receptor expressed by M2 macrophage). The efficacy of this immunomodulatory implant was further demonstrated in an in vivo rat model. The animal study showed that the presence of IL-4 diminished the capsule thickness, the amount of collagen, tissue inflammation, and the infiltration of fibroblasts and myofibroblasts. These results suggest that macrophage phenotype modulation can effectively reduce inflammation and fibrous CC on a silicone implant conjugated with IL-4.