Follistatin and the Breast Implant Capsule

Abstract

Background: Breast capsular contracture remains an elusive problem faced by plastic surgeons and is the leading long-term complication after breast implantation. Follistatin (Fst) is a protein with known anti-inflammatory and antifibrotic properties and has the potential to limit the severity of diseases associated with inflammation and fibrosis such as capsular contracture. The aim of this study was to examine the effect of Fst288 on capsular fibrosis around silicone implants in a mouse model.

Methods: BALB/c mice were implanted subcutaneously with untreated silicone implants (baseline control). In the experimental group, immediately after silicone implant insertion, the implant pocket received either a single injection of 1 µg Fst288 or normal saline (internal control). The animals were killed at 3, 5, 7, 14, 28, and 90 days after surgery, and serum, implants, and the surrounding tissue were removed for histological and immunohistochemical analyses.

Results: Fst288 treatment resulted in significant decreases in capsule thickness at 28 days (P < 0.05) and 3 months (P < 0.001), decreased collagen production at 14 days (P < 0.05) and 3 months (P < 0.01), decreased angiogenesis at 3 months (P < 0.001), decreased α-smooth muscle actin levels at 3 months (P < 0.05), and a decrease in the number of CD45+ cells at days 5 (P < 0.05) and 7 (P < 0.01), respectively, when compared with control implants.

Conclusions: A single injection of Fst288 at the time of silicone implant insertion into the mice results in a significant reduction in pericapsular inflammation and capsular fibrosis.

Fig. 1.

Data obtained using Masson trichrome staining to facilitate measurement of capsule thickness (µm) at days 14, 28, and 90 in (A) baseline group and (B) Fst implant group. Results are expressed as mean ± standard error of the mean.

Fig. 2.

Masson trichrome staining showing capsule thickness (µm) at (A) 3 months, mouse 4, control (20×) and (B) 3 months, mouse 4, Fst 288 (20×). Ca, capsule; IC, implant cavity; M, muscle.

Fig. 3.

Masson trichrome staining showing ECM production (collagen stained blue) in (A) 3 month, mouse 5, control (20×) and (B) 3 months, mouse 5, Fst 288 (20×). Ca, capsule; IC, implant cavity; M, muscle.

Fig. 4.

ECM formation (percentage Masson positive tissue per HPF) at days 14, 28, and 90 in (A) baseline group and (B) Fst implant group. Results are expressed as mean ± standard error of the mean. HPF, high-powered field.

Fig. 5.

Angiogenesis (average vessels per HPF) at days 14, 28, and 90 in (A) baseline group and (B) Fst implant group. Results are expressed as mean ± standard error of the mean. HPF, high-powered field.

Fig. 6.

Immunohistochemistry analysis of α-SMA staining at 3 months (percentage of α-SMA–positive tissue per HPF) (A) baseline group and (B) Fst implant group. Results are expressed as mean ± standard error of the mean. HPF, high-powered field.

Fig. 7.

Immunohistochemistry analysis of CD45 staining (percentage of CD45-positive cells per high-powered field) in (A) baseline group and (B) Fst implant group. Results are expressed as mean ± standard error of the mean.

Fig. 8.

Tissue levels of (A) IL-6 baseline group, (B) IL-6 Fst implant group, (C) activin A, baseline group, (D) activin A, Fst implant group, (E) Fst288, baseline group, and (F) Fst288, Fst implant group. Data expressed as mean ± standard error of the mean.