The Role of Verteporfin in Prevention of Periprosthetic Capsular Fibrosis: An Experimental Study.

Abstract

Capsular contracture (CC) characterized by excessive fibrosis is one of the most common complications after silicone implant surgery. Verteporfin (VP), an inhibitor of Yes-associated protein 1 (YAP1), has recently been found to reduce the fibrotic process. The aim of this study was to use an in vivo rabbit model to evaluate the efficacy of VP for the prevention of CC. Twenty-four New Zealand rabbits received 10-cc smooth saline silicone implants inserted in the dorsal skin and were randomly divided into 2 groups to receive 2 mL VP (1.5 mg/mL) or 2 mL phosphate-buffered saline solution instillation in the implant pocket. When the animals were killed on Day 60, capsule formation was observed both macroscopically and microscopically. Histologic evaluation included capsule thickness, fibrosis degree, and myofibroblast (α smooth muscle actin positive) content. In addition, the YAP1 expression level was examined by immunofluorescence staining. Transforming growth factor β1, collagen I, and connective tissue growth factor expression were measured by real-time quantitative polymerase chain reaction. The VP-treated group exhibited thinner, more transparent capsules and less fibrosis than the control group at 60 days postsurgery (P < 0.05). Moreover, the VP treatment significantly reduced α smooth muscle actin, YAP1, transforming growth factor β1, collagen I, and connective tissue growth factor expression levels in the capsular tissues (P < 0.05). VP reduced capsule formation after silicone implantation by inhibiting YAP1-mediated mechanical signaling, thereby attenuating excessive collagen deposition in the rabbit model. This preclinical study may provide a feasible strategy to prevent periprosthetic capsular fibrosis in clinical application.