A RHAMM Peptide Mimetic Reduces Capsule Fibrosis in a Novel Rodent Model of Radiation-Induced Capsular Contracture.

Abstract

Capsular contracture is a common complication of implant-based breast reconstructive surgery and is especially challenging in the setting of post-mastectomy radiation. The objective of this study was two-fold; first to develop a novel rat model of radiation-induced capsular contracture, and then second, to use this model to evaluate the effect of a RHAMM function-blocking peptide mimetic, NP-110, on capsule fibrosis. The model consisted of female retired breeder Sprague Dawley rats (7 radiated, 7 controls) that underwent surgery to place a custom 2 cc silicone implant under the right fourth mammary fat pad. The implant, mammary fat pad, and overlying skin were then treated with 26 Gy of targeted ionizing radiation in 7 rats, which resulted in clinically, histologically, and biochemically measurable capsule fibrosis in all irradiated animals compared to non-radiated controls. A second cohort (n=14) received a local injection of NP-110 or scrambled control peptide (100µg/rat), followed by 26 Gy of targeted ionizing radiation. Clinically, NP-110 treated animals showed decreased post-radiation fibrotic change. A significantly decreased collagen deposition and bundling in the NP-110 group (p <0.001) was demonstrated by Mason's trichrome and Picrosirius red staining and had significantly less aSMA in capsule tissue compared to the scrambled peptide control (p=0.02). This study demonstrates a novel, orthotopic and replicable animal model for radiation-induced capsular contracture and identifies RHAMM as a potential target for development of preventative therapeutic agents to manage post radiotherapy capsular contracture.