Title: A Novel Animal Model to Study Capsular Contracture Utilizing Livescan MicroCT Technology

Background

Capsular contracture remains one of the major problems following prosthetic implantation of the breast, especially in post-mastectomy breast reconstruction patients receiving radiation therapy. Advances in this area have been hampered by the absence of an acceptable animal model. This study evaluates a new murine model in order to facilitate research into the cellular and molecular pathways underlying capsular contracture and provide a surrogate to evaluate potential therapies.

Methods

On day 0, 16 C57BL/6 wildtype mice were implanted with bilateral 300mg silicone gel implants (Mentor, Inc.). Postoperatively, all animals were imaged using livescan μCT to evaluate the initial shape and orientation of the implants. Animals in the non-irradiated arm then returned to the vivarium while animals in the radiation arm received a 10 gray directed radiation dose from a slit beam cesium source. The targeted radiation is designed to induce capsular contracture while avoiding systemic effects of radiation. On day 21, both irradiated and non-irradiated animals were imaged again.  Animals were then sacrificed for histological evaluation. 

Results

Implants from the non-irradiated group demonstrated very little change in shape between days 0 and 21 on μCT. In contrast, irradiated implants demonstrated consistent shape deformation (figure 1). Non-irradiated histological specimens from day 21 showed a thin, uniform, and well organized collagen capsule surrounding the implants, whereas irradiated specimens had thickened irregular capsules composed of disorganized collagen fibers (figure 2).  

Conclusions

Here, we introduce a novel animal model to study capsular contracture. This model is the first of its kind to use radiation to induce and livescan μCT to evaluate capsular contracture. At this early time point, radiation was shown to cause reproducible changes that can be consistently evaluated with μCT and histology. Future studies with this model will study the cellular and molecular mechanisms underlying capsular contracture using knockout and transgenic mouse strains.