Immunohistochemical Analysis of Capsular Contracture in Silicone Implant Rhinoplasty

Silicone implant-based augmentation rhinoplasty or mammoplasty induces capsular contracture, which has been acknowledged as a process that develops an abnormal fibrotic capsule associated with the immune response to allogeneic materials. However, the signaling pathways leading to the nasal fibrosis remain poorly investigated. We aimed to explore the molecular mechanism underlying the pathogenesis of nasal capsular contracture, with a specific research interest in the signaling pathways involved in fibrotic development at the advanced stage of contracture. By examining our recently obtained RNA sequencing data and global gene expression profiling between grade II and grade IV nasal capsular tissues, we found that both the RAP1 and JAK/STAT signaling pathways were hyperactive in the contracted capsules. This was verified on quantitative real-time PCR which demonstrated upregulation of most of the representative component signatures in these pathways. Loss-of-function assays through siRNA-mediated Rap1 silencing and/or small molecule-directed inhibition of JAK/STAT pathway in ex vivo primary nasal fibroblasts caused a series of dramatic behavioral and functional changes, including decreased cell viability, increased apoptosis, reduced secretion of proinflammatory cytokines, and synthesis of type I collagen, compared to control cells, and indicating the essential role of the RAP1 and JAK/STAT signaling pathways in nasal capsular fibrosis. Our results sheds light on targeting downstream signaling pathways for the prevention and therapy of silicone implant-induced nasal capsular contracture.

Download Full-text

The Role of Periostin in Capsule Formation on Silicone Implants

BioMed Research International ◽

10.1155/2018/3167037 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Hahn-Sol Bae ◽

Hye-Youn Son ◽

Jung Pyo Lee ◽

Hak Chang ◽

Ji-Ung Park

Keyword(s):

Collagen Type ◽

Capsular Contracture ◽

Fibrous Tissue ◽

Immunohistochemical Analysis ◽

Inflammatory Cells ◽

Collagen Type I ◽

Silicone Implants ◽

Type I ◽

Capsule Formation

Although silicone implants are widely used in breast and other reconstructive surgeries, the limited biocompatibility of these materials leads to severe complications, including capsular contracture. Here, we aimed to clarify the relationship between periostin and the process of capsule formation after in vivo implantation. Seven-week-old wild-type (WT) C57BL/6 mice and periostin-deficient mice were used. Round silicone implants were inserted into a subcutaneous pocket on the dorsum of the mice. After 8 weeks, the fibrous capsule around the implant was harvested and histologically examined to estimate capsular thickness and the number of inflammatory cells. Additionally, immunohistochemical analysis (periostin, α-SMA, and collagen type I) and western blotting (CTGF, TGF-β, VEGF, and MPO) were performed for a more detailed analysis of capsule formation. The capsules in periostin-knockout mice (PN-KO) were significantly thinner than those in WT mice. PN-KO mice showed significantly lower numbers of inflammatory cells than WT mice. Fibrous tissue formation markers (α-SMA, periostin, collagen type I, and CTGF) were significantly reduced in PN-KO mice. We also confirmed that inflammatory reaction and angiogenesis indicators (TGF-β, MPO, and VEGF) had lower expression in PN-KO mice. Inhibition of periostin could be important for suppressing capsule formation on silicone implants after in vivo implantation.

Download Full-text

Optimization of Oxygen Plasma Treatment of Silicone Implant Surface for Inhibition of Capsular Contracture

Journal of Industrial and Engineering Chemistry ◽

10.1016/j.jiec.2021.02.004 ◽

2021 ◽

Author(s):

Shin Hyuk Kang ◽

Chanutchamon Sutthiwanjampa ◽

Hyeon Seok Kim ◽

Chan Yeong Heo ◽

Mi Kyung Kim ◽

...

Keyword(s):

Plasma Treatment ◽

Oxygen Plasma ◽

Capsular Contracture ◽

Silicone Implant ◽

Oxygen Plasma Treatment ◽

Implant Surface

Download Full-text

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

Polymers ◽

10.3390/polym13162630 ◽

2021 ◽

Vol 13 (16) ◽

pp. 2630

Author(s):

Hyun-Seok Kim ◽

Seongsoo Kim ◽

Byung-Ho Shin ◽

Chan-Yeong Heo ◽

Omar Faruq ◽

...

Keyword(s):

Tissue Regeneration ◽

Capsular Contracture ◽

Silicone Implant ◽

Interleukin 4 ◽

Silicone Implants ◽

M2 Macrophage ◽

Macrophage Phenotype ◽

Arginase 1

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.

Download Full-text