Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules

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) macr...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/13/16/2630
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author 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
author_facet 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
author_sort Hyun-Seok Kim
collection DOAJ
description 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.
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spelling doaj.art-9d3e2bc920174d819490508efb013a4c2023-11-22T09:21:55ZengMDPI AGPolymers2073-43602021-08-011316263010.3390/polym13162630Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous CapsulesHyun-Seok Kim0Seongsoo Kim1Byung-Ho Shin2Chan-Yeong Heo3Omar Faruq4Le Thi Van Anh5Nilsu Dönmez6Pham Ngoc Chien7Dong-Sik Shin8Sun-Young Nam9Rong-Min Baek10Department of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, KoreaDivision of Chemical and Bioengineering, Kangwon National University, Chuncheon 24341, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Chemical and Biological Engineering, Sookmyung Women’s University, Seoul 04310, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, KoreaDepartment of Plastic and Reconstructive Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, KoreaBreast 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.https://www.mdpi.com/2073-4360/13/16/2630silicone implantsimmobilization of IL-4capsular contracturefibrosisinflammationmacrophage polarization
spellingShingle 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
Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
Polymers
silicone implants
immobilization of IL-4
capsular contracture
fibrosis
inflammation
macrophage polarization
title Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
title_full Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
title_fullStr Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
title_full_unstemmed Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
title_short Silicone Implants Immobilized with Interleukin-4 Promote the M2 Polarization of Macrophages and Inhibit the Formation of Fibrous Capsules
title_sort silicone implants immobilized with interleukin 4 promote the m2 polarization of macrophages and inhibit the formation of fibrous capsules
topic silicone implants
immobilization of IL-4
capsular contracture
fibrosis
inflammation
macrophage polarization
url https://www.mdpi.com/2073-4360/13/16/2630
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