Surface Modification of Silicone Breast Implants by Binding the Antifibrotic Drug Halofuginone Reduces Capsular Fibrosis

Zeplin, Philip H.; Larena-Avellaneda, A.; Schmidt, Karsten

doi:10.1097/prs.0b013e3181dbc313

Cited by 47 publications

(38 citation statements)

References 45 publications

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“…Whereas during the systemic application of HF partly strong gastrointestinal complaints have been described [39,43]. Recent studies could already elucidate a significant local reduction of the TGF-beta-1-and COL1A1-expression through submuscular implantation of a HF coated silicone implant [44]. The present study demonstrates that the local effect of HF is not only limited on TGF-beta-1 and collagen-I, but also affects the pro-angiogenic factors bFGF and MMP-2, however not MMP-9.…”

Section: Discussionmentioning

confidence: 98%

Local inhibition of angiogenesis by halofuginone coated silicone materials

Jordan

Zeplin

2012

J Mater Sci: Mater Med

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Anti-angiogenic therapy is a promising approach for the treatment of increased angiogenesis in certain diseases. We aimed to investigate the local anti-angiogenic effect of silicone implants coated with Halofuginone, an angiogenesis inhibitor that inhibits synthesis of collagen-type-I and matrix metalloproteinases. The degree of angiogenesis was observed after implantation of surface modified Halofuginone eluting silicone implants into a submuscular pocket in rats over a period of 3 months. Subsequently, key mediators of angiogenesis (TGF-beta-1, bFGF, COL1A1, MMP-2, MMP-9, VEGF and PDGF) were established by immunohistological staining and RT-PCR and statistically evaluated. In comparison to uncoated silicone implants, Halofuginone eluting silicone implants lead to a significant local decrease of angiogenesis. Halofuginone eluting hybrid surface silicone implants have a significant local anti-angiogenic effect by down-regulating the expression activity of key mediators of angiogenesis.

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Section: Discussionmentioning

confidence: 98%

Local inhibition of angiogenesis by halofuginone coated silicone materials

Jordan

Zeplin

2012

J Mater Sci: Mater Med

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“…To examine the effects of montelukast in reducing the occurrence of capsular contracture, we histopathologically examined the thickness of the capsule and the number of inflammatory cells. Philip et al [21] performed an experimental study to examine the effects of reducing the occurrence of capsular fibrosis, according to which, of various quantitative factors indicating the degree of the formation of myofibroblasts that are the factors most responsible for the occurrence of capsular contracture, TGF-β (one of the key cytokines that are involved in the cellular growth and differentiation and the synthesis of extracellular matrix) has been identified as the most important substance. Thus, by provoking the occurrence of the chronic inflammations, it causes the formation of granulation tissue and fibrosis [22].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

et al. 2013

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Background and Purposes: Capsular contracture is one of the most severe complications that can occur in breast surgery following silicone implant insertion. The purpose of this study was to investigate the effect of montelukast and antiadhesion barrier solution (AABS) on reducing capsular formation and their possible synergism. Materials andMethods: This study was approved by the Animal Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with the Kyungpook National University - Institutional Animal Care and Use Committee, Animal Ethics Committee. The experiments in this study were conducted in vivo in 4 groups of 24 rats. Following silicone implant insertion, the pocket was injected with different agents. Group I (control group) was given normal saline injections into the pocket and fed with pure water. Group II was given injections of AABS and fed with pure water. Group III was given injections of normal saline and the medication montelukast during the experimental period. Group IV was given injections of AABS and montelukast as postoperative medication. Peri-implant capsules were excised after 8 weeks and were evaluated for transparency, inflammatory cell content, capsule thickness, collagen pattern and TGF-β expression. Results: The capsules in the experimental groups (i.e., groups II-IV) were significantly more transparent than those in group I (controls; p < 0.05, Student's t test). The mean capsule thickness of the experimental groups II (296 ± 14.76 μm), III (280 ± 14.77 μm) and IV (276 ± 39.28 μm) was smaller than that of the control group I (361 ± 35.43 μm). Compared to the control group, the histologic findings in the experimental groups suggested a decreased inflammatory response occurring in the peri-implant capsules as they exhibited minor vascularization and a reduced number of mast cells and macrophages. The collagen patterns in the experimental groups were of a lower density than in the control group with the former showing a loose, tidy collagen pattern. The amounts of TGF-β and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. Conclusions: Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-β, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

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“…8,13,14 It has been demonstrated that Halofuginone reduces fibrosis formation in many pathological conditions. 8,[13][14][15][16][17][18][19] Previously Halofuginone has shown to reduce fibrosis in mice models with stretched skin due to scleroderma 20 , to decrease in the liver fibrosis model due to thiacetamide 21 , to lessen graft versus host disease 22 , to improve muscular dystrophies including dysferlinopathy 19,23 , and lessen mesangial cell proliferation and matrix deposition in the kidney. 24 By the light of these studies, we hypothesized that Halofuginone may be able to ameliorate radiation-induced cardiovascular injury.…”

Section: Discussionmentioning

confidence: 99%

The effect of halofuginone on radiation-induced cardiovascular injury

Yavaş¹,

Çalık

Yavaş

et al. 2015

Int J Cancer Ther Oncol

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Purpose: The main purpose of this study was to evaluate the effects of Halofuginone on radiation-induced cardiovascular injury in a rat model. Methods: Sixty Wistar-Albino rats were divided into six groups (the control group, radiotherapy (RT) only group Irradiation (IR), 2.5 and 5 μg Halofuginone groups (Hal (2.5)/C and Hal (5.0)/C), and RT plus 2.5 and 5 μg Halofuginone groups (Hal (2.5)/IR and Hal (5.0)/IR). Rats were exposed to a single dose of 12 Gy irradiation generated by a linear accelerator. Halofuginone was applied intraperitoneally with daily doses. At the 6 th and 16 th weeks of RT, 5 rats from each group sacrificed and; heart and thoracic aorta tissues removed for both light microscopic and electron microscopic examinations. Results: Light microscopic examinations revealed that the endocardial thickness of all study groups was significantly different at 6 th and 16 th week of RT (p < 0.001 for both). Pair-wise comparisons showed that the differences were significant in IR-Hal (2.5)/IR (p < 0.001); IR-Hal (5.0)/IR (p < 0.001); and Hal (2.5)/IR-Hal (5.0)/IR (p = 0.001) at 16 th week of RT. There were significant differences within the study groups regarding to the thoracic aorta fibrosis scores only at 16 th week of RT (p = 0.002). Electron microscopic examinations demonstrated that there were significant differences between all the groups with respect to heart mitochondria scores at both 6 th week and 16 th weeks of RT (p < 0.001 for both). The differences between Hal (2.5)/IR and Hal (5.0)/IR with respect to the heart mitochondria scores were significant only at 16 th week of RT (p = 0.001). Conclusion: These data demonstrated that Halofuginone may improve radiation-induced cardiovascular injury. The most prominent improvement was observed in higher dose of Halofuginone group after long term follow-up.

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Surface Modification of Silicone Breast Implants by Binding the Antifibrotic Drug Halofuginone Reduces Capsular Fibrosis

Abstract: The results confirmed a decrease in foreign body responses to halofuginone surface-modified silicone implants and mark their potential for obtaining a lessened capsular fibrosis by way of a local antifibrotic effect.

Cited by 47 publications

References 45 publications

Local inhibition of angiogenesis by halofuginone coated silicone materials

Local inhibition of angiogenesis by halofuginone coated silicone materials

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

The effect of halofuginone on radiation-induced cardiovascular injury

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