Simvastatin Reduces Capsular Fibrosis around Silicone Implants

Abstract

Capsular fibrosis and contracture occurs in most breast reconstruction patients who undergo radiotherapy, and there is no definitive solution for its prevention. Simvastatin was effective at reducing fibrosis in various models. Peri-implant capsular formation is the result of tissue fibrosis development in irradiated breasts. The purpose of this study was to examine the effect of simvastatin on peri-implant fibrosis in rats. Eighteen male Sprague-Dawley rats were allocated to an experimental group (9 rats, 18 implants) or a control group (9 rats, 18 implants). Two hemispherical silicone implants, 10 mm in diameter, were inserted in subpanniculus pockets in each rat. The next day, 10-Gy of radiation from a clinical accelerator was targeted at the implants. Simvastatin (15 mg/kg/day) was administered by oral gavage in the experimental group, while animals in the control group received water. At 12 weeks post-implantation, peri-implant capsules were harvested and examined histologically and by real-time polymerase chain reaction. The average capsular thickness was 371.2 μm in the simvastatin group and 491.2 μm in the control group. The fibrosis ratio was significantly different, with 32.33% in the simvastatin group and 58.44% in the control group (P < 0.001). Connective tissue growth factor (CTGF) and transforming growth factor (TGF)-β1 gene expression decreased significantly in the simvastatin group compared to the control group (P < 0.001). This study shows that simvastatin reduces radiation-induced capsular fibrosis around silicone implants in rats. This finding offers an alternative therapeutic strategy for reducing capsular fibrosis and contracture after implant-based breast reconstruction.

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Biodegradable polymerized simvastatin stimulates bone formation

“…This could be attributed to the antifibrotic effects of the released simvastatin. Earlier reports have shown that simvastatin reduces capsular fibrosis around silicone implants when administered orally, by downregulating the expression of connective tissue growth factor (CTGF) and transforming growth factor (TGF)β 1 genes in rodents [23]. Further, resolution of hematoma could be attributed to the fact that simvastatin facilitates its absorption via phagocytosis by increasing the expression of CD36 (cluster of differentiation 36) [24].…”

Pharmacological Approaches for the Prevention of Breast Implant Capsular Contracture

“…137 In a later study testing higher oral doses of simvastatin in rats (15 mg/kg/d), radiation-induced capsular fibrosis around silicone implants was significantly reduced compared with a control group. 138…”