Antifibrotic Agents for Silicone Implant Capsular Contracture: A Study on Nintedanib and Pirfenidone in Rats

Capsular contracture is a frequent complication after breast implantation, often requiring revision surgery with high recurrence. Fibrosis and chronic inflammation are central to its pathogenesis; thus, antifibrotic pharmacological modulation is a promising preventive strategy. This study evaluated the effects of pirfenidone and nintedanib on capsular contracture in a rat model.

Twenty-seven female Wistar albino rats were divided into control, pirfenidone, and nintedanib groups. Silicone block implants were placed under the panniculus carnosus. Pirfenidone (100 mg/kg/day) and nintedanib (50 mg/kg/day) were administered orally for eight weeks. At the end of the nine-week study period, the animals were euthanized, and the implants with the surrounding capsules were harvested for histological and immunohistochemical analyses. Capsular thickness and inflammatory cell counts were assessed histologically, while α-SMA expression and TGF-β expression were evaluated by immunohistochemistry. Collagen density and organization were examined using Masson's trichrome staining. Nonparametric tests were used for statistical analysis due to non-normal data distribution.

Both drugs significantly reduced capsular thickness, inflammatory cell infiltration, α-SMA, and TGF-β expression compared to control (p<0.001). Nintedanib showed significantly thinner capsules and lower α-SMA expression than pirfenidone (p<0.001), indicating stronger inhibition of fibrosis. Histological evaluation showed dense collagen fibers in the control group, while treatment groups had thinner, irregular collagen, most notably in the nintedanib group.

Both agents significantly reduced fibrosis-related parameters compared with the control group. Compared with pirfenidone, nintedanib produced greater reductions in capsule thickness and α-SMA expression, whereas inflammatory cell counts and TGF-β expression were comparable between the two treatment groups.

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