Effect of Tissue Inhibitors of Metalloproteinases and Matrix Metalloproteinases on Capsular Formation Around Smooth and Textured Silicone Gel Implants

Abstract

Capsular contracture is one of the most distressing complications after cosmetic breast augmentation. Evidence suggests that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may play a key role in the onset or progression of several fibrotic disorders. In this study we used quantitative reverse-transcription PCR methodology to profile the expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 in the tissue of patients with capsular contracture after breast augmentation with smooth and textured silicone breast implants. The study included 20 female patients (average age = 37 +/- 15 years) with capsular contracture after bilateral subglandular cosmetic breast augmentation with smooth silicone implants. Ten patients developed grade II capsule contracture, 8 grade III contracture, and 1 grade IV contracture. Twenty other female patients (average age = 41 +/- 9 years) with capsular contracture after breast augmentation with textured silicone implants were also included (Baker grade II = 10 patients, grade III = 8, grade IV = 2). Expression of mRNA in capsular tissue was calculated using a relative quantification method (Pfaffl). Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be p < 0.05. The expression of MMP-2 was significantly increased in tissue of patients with textured implants and capsular contracture grades II and III/IV in comparison to grade I (p < 0.05). In comparison to grade I, the capsular tissue from patients with Baker II and III/IV fibrosis showed a significant increase for TIMP-1 and TIMP-2 (p < 0.05) in both smooth and textured silicone implants. The expression was significantly higher in tissue from patients with severe contracture (Baker III/IV) and smooth silicone implants compared with that in tissue from patients with textured implants (p < 0.05). The decrease in MMP-to-TIMP expression can cause increased synthesis and deposition of collagen surrounding alloplastic breast implants, leading to a profibrotic state. The higher expression of TIMPs in capsular tissue of patients with smooth silicone gel implants might be a reason for the observed higher rates of capsular contracture. In the future, a nonoperative treatment that decreases TIMPs but increases the activity of MMPs may be an appropriate therapy for patients with capsular contracture.