A Novel Small Molecule Breast Implant Surface Coating Significantly Reduces Peri-Prosthetic Capsule Formation
Sarah J. Karinja, BA1, Alexandra Lin, BA1, Omid Veiseh, PhD2, Jaime L. Bernstein, BS1, Julia Jin, BS1, Andrew Abadeer, MEng1, Omer Kaymakcalan, MD1, Robert S. Langer, ScD3, Daniel G. Anderson, PhD3, Jason A. Spector, MD1.
1Weill Cornell Medical College, New York, NY, USA, 2Sigilon, Inc., Cambridge, MA, USA, 3Massachusetts Institute of Technology, Cambridge, MA, USA.
BACKGROUND: Capsular contracture (CC), the progressive growth and contraction of the foreign body response-formed peri-prosthetic capsule, is the most common complication of aesthetic and reconstructive breast surgery, affecting up to 47.5% of patients (1). CC is the cause of significant patient morbidity, including breast pain, hardening, and deformity. 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. In fact, CC is the most common indication for revision surgery after implant-based breast surgery. CC is thought to be due to an excessive foreign body response, an inflammatory reaction coordinated by macrophages which culminates in fibroblast peri-prosthetic collagen deposition. As such, herein we altered the surface chemistry of silicone implants with proprietary anti-inflammatory molecules, E9 and RZA15, which are designed to reduce immune cell adhesion to the implant, leading to a truncated foreign body response. As these molecules have shown promise in reducing fibrosis around artificial islet cell constructs, we hypothesized that covalent grafting of these biocompatible small organic molecules to the silicone implant surface would reduce capsule formation, and thus reduce capsular contracture.
METHODS: Round silicone implants were created from polydimethylsiloxane (PDMS). The surface was modified with covalent bonding of RZA15 or E9, Sigilon's anti-inflammatory proprietary molecules. Uncoated, RZA15- and E9-coated implants were implanted into wildtype C57Bl/6 mice, according to Katzel et al. with slight modifications to recapitulate CC in a murine model (2). After 21 and 90 days, peri-prosthetic tissue was removed for histologic analysis, and stained with Hematoxylin & Eosin and Masson's Trichrome. The capsule was identified, outlined in ImageJ software, capsule area calculated and divided by capsule length to determine capsule thickness. This was repeated for five regions per implant, to calculate a mean capsule thickness per implant.
RESULTS: We compared mean capsule thickness at two time points across the three groups: E9-coated, RZA15-coated, and uncoated implants. After 21 days, there was a statistically significant reduction in capsule thickness of RZA15- (71.12 microns; p = 0.0194) and E9-coated implants (76.84 microns; p = 0.0463) compared to uncoated implants (103.80 microns). Similarly, after 90 days, there was a statistically significant reduction in capsule thickness E9-coated implants (40.51 microns; p = 0.023) compared to uncoated implants (59.16 microns).
CONCLUSION: Coating the surface of silicone breast implants with RZA15 and E9 significantly reduced capsule formation in a mouse model for implant-based breast augmentation and reconstruction at both 3 weeks and 3 months post-operatively. These results suggest capsular contracture itself may be significantly attenuated as capsule formation obligatorily precedes capsular contracture. 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.
REFERENCES: 1. Rella L, et al. MRI evaluation of post-mastectomy irradiated breast implants: prevalence and analysis of complications. Clinical Radiology 2015;70:948-53. 2. Katzel E, et al. A novel animal model for studying silicone gel-related capsular contracture. PRS 2010;126(5):1483-91.
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