Optimizing the radiation dose in a murine model of breast implant capsular fibrosis

Breast implant capsular contracture (CC) is the leading complication following reconstructive breast surgery, especially in breast cancer patients who undergo radiotherapy after reconstruction surgery. The exact pathophysiology of this complication is unclear with limited treatment options and high-quality research models are greatly needed. Here, we aimed to determine the optimal protocol to create an easily reproducible murine model that recapitulates the effects of radiotherapy following breast implantation. We implanted smooth mini silicone breast implants into a dorsal subcutaneous pocket of 8-week-old, female C57Bl/6 mice. Then, we immediately applied a directed dose of 10-Gy (N = 11), and 15-Gy (N = 11) slit-beam radiation to the implanted area along with non-irradiated mice (N = 11). The follow-up period was 42 -days post-radiation after which histological and tissue gene expression studies were done. Circulating TGF-b concentrations were also measured. Radiation therapy led to a significant decrease in total body weight and was proportional to the radiation dose. The 10-Gy dose of targeted radiotherapy significantly increased mean capsular thickness measured at 42 days following the procedure. However, mice who received a 15-Gy dose did not present with increased mean capsular thickness compared with implant-only mice. The 10-Gy dose upregulated pro-fibrotic and pro-inflammatory genes such as Collagen-3 and TIMP1 while the 15-Gy dose did not. Targeted radiotherapy with a 10-Gy and not 15-Gy dose in implanted mice induced significant CC along with an elevated pro-fibrotic response. Our findings demonstrate the successful development of a robust mouse model of breast implant CC using a 10-Gy unfractionated dose of radiotherapy immediately after implant insertion.