Effect of the First Epidermal Growth Factor Motif of Coagulation Factor 9 on Capsular Formation Around Silicone Implants

PURPOSE: Capsular contracture is one of the most serious complications after cosmetic breast augmentation or breast reconstruction. However, there is no effective prophylactic or treatment method for capsular contracture. In recent years, it has been found that coagulation factors have functions other than those related to coagulation activity. We have found that the epidermal growth factor (EGF) derived from coagulation factor 9 (EGF-F9) has an antifibrotic effect, among other functions. The purpose of this study was to investigate whether EGF-F9 can inhibit capsular formation in a rat implant insertion model.

METHODS; EGF-F9 was prepared from cDNA of a mouse F9 deletion mutant and AP-tag 4 vector. This study used 8 male 7-week-old Sprague Dawley rats. A 2-cm incision was made at 2 places on the back of the rat to create a subcutaneous pocket. A 2 × 2 cm implant made from a smooth type tissue expander was inserted into the pocket. A control group (untreated) (n = 8) and a treated group (n = 8) were prepared. In the control group, 0.1 ml of phosphate buffered saline (PBS) was instilled into one pocket and 50 pM/0.1 ml of EGF-F9 was instilled into the other pocket. In both groups, PBS or EGF-F9 was injected into subcutaneous tissue overlying the implant three times a week.  Tissue was collected on day 28 after surgery, and the thickness of the capsule was measured and histologically examined.

RESULTS: The mean thickness of the capsule in the control group and treated group was 95.3±47.8 μm and 48.1±12.8 μm, respectively. The capsule was significantly thinner in the treated group (p<0.05). In immunostaining, matrix metalloproteinase 9 (MMP 9) showed increased expression in the treated group  and alpha smooth muscle actin (ASMA) showed increased expression in the control group.

CONCLUSIONS: The administration of EGF-F9 inhibited the formation of a capsule around the silicone implant. EGF is involved in the control of MMP expression and differentiation into myofibroblasts. It was suggested that administration of EGF-F9 suppressed the formation of the capsule by increasing local MMP 9 and regulating differentiation into myofibroblasts.