Abstract: A Novel Breast Implant Surface Chemistry Significantly Reduces Acute and Chronic Peri-Prosthetic Capsule Formation in a Murine Model

Abstract

INTRODUCTION: Capsular contracture (CC) is the most common complication of implant-based breast surgery and the source of significant patient morbidity. Yet, there are no clinically approved therapies for prevention or treatment of CC. Rather, the complication is mitigated with re-operation and capsule excision, which often necessitates implant removal and replacement. The mechanism underlying CC remains unknown, however is understood to involve an excessive and pathologic foreign body response (FBR). As such, herein we coated the surface of silicone implants with proprietary, anti-inflammatory, anti-fibrotic molecules developed by Sigilon, Inc. We hypothesized that covalently bonding these novel anti-inflammatory molecules to silicone implants would reduce the FBR for the lifetime of the implant, thus reducing later downstream effects of capsule formation and CC. METHODS: Silicone implants were created from polydimethylsiloxane and coated with RZA15 or E9, two biocompatible and non-degradable, anti-fibrotic, proprietary molecules. Uncoated, RZA15- and E9-coated implants were implanted subcutaneously into the dorsa of wildtype C57Bl/6 mice. After 21, 90 and 180 days (equal to approximately 3, 10 and 20 years post-operatively in human years) peri-prosthetic tissue was removed for histologic analysis, and stained with Hematoxylin & Eosin and Masson’s Trichrome. The capsule was identified at five equidistant regions throughout the implant and outlined in ImageJ software. Capsule area was calculated, and divided by capsule length to determine the average capsule thickness per implant. RESULTS: We compared mean capsule thickness at three time points across the three groups: E9-coated, RZA15-coated, and uncoated implants. At 21, 90 and 180 days, there was a statistically significant reduction in capsule thickness of RZA15- and E9-coated implants compared to uncoated implants (p < 0.05). CONCLUSION: Coating the surface of silicone implants with RZA15 and E9 significantly reduced acute and chronic capsule formation in a mouse model for implant-based breast augmentation and reconstruction. As capsule formation obligatorily precedes capsular contracture, these results suggest contracture itself may be significantly attenuated. Furthermore, as peri-prosthetic capsule formation is a complication without anatomical boundaries, the chemistry of this novel compound may have additional applications beyond breast implants, to a myriad of other implantable medical devices.