179. Altered Foreign Body Response at the Posterior Surface Compared to the Anterior Surface of Human Silicone Breast Implants

PURPOSE: Dysregulation of the foreign body reaction (FBR) and chronic peri-prosthetic inflammation of the breast implant-tissue interface is linked to several pathologies including capsular contracture, breast implant associated-anaplastic large cell lymphoma (BIA-ALCL) and squamous cell carcinoma (SCC). The FBR and resulting capsule have long been assumed to be uniform. However, the implant is asymmetric and placed in a non-uniform implant pocket with differential anterior and posterior mechanical factors, which have been shown to alter the FBR. Currently, little is known about how these spatial factors influence capsule physiology, how they progress over time, and their impact on the implant itself. The purpose of our study was to: 1) compare inflammatory and fibrotic phenotypes of anterior and posterior human breast implant capsule 2) determine how duration of implantation alters these phenotypes, and 3) investigate whether there are corresponding oxidative changes to the device surface. METHODS: We collected human breast implant capsule and removed implants from reconstructive patients undergoing secondary surgery at McGill University Health Center hospital (September 2020 and April 2022). Within each breast, both anterior (N = 31) and posterior (N = 31) capsule were collected. Specimens were assessed histologically for capsular thickness and collagen organization. Capsular cell populations were measured by immunohistochemistry for fibroblasts (vimentin), myofibroblasts (α-smooth muscle actin), total macrophages (CD68), M1 macrophages (iNOS) and M2 macrophages (CD206). Expression of proinflammatory cytokines (IL-1β, IL-6), extracellular matrix (Col1, Col3) and profibrotic growth factor TGF-β were measured with RT-PCR. Samples of anterior (N = 17) and posterior (N=17) breast implant surface were assessed for oxidation with XPS analysis. Statistical analyses included paired t-tests and simple linear regression. RESULTS: We demonstrate that posterior capsule displays several features of a dysregulated FBR compared to anterior capsule. These features include: 1) significantly increased capsule thickness (p <.05), 2) abnormal extracellular matrix remodeling characterized by disorganized collagen organization (p <.05) and increased immature type 3 collagen expression (p <.05), and 3) increased infiltration of macrophages (p <.05). We also show that posterior capsule becomes more dysregulated over time as evidenced by a significant positive relationship between pro-inflammatory cytokines IL-1 β and IL-6 and implant duration (p <.05). Finally, posterior device surface was significantly more oxidized than that anterior device surface (p <.05) suggesting that corresponding changes occur at the level of the implant that may ultimately compromise the integrity of the device. CONCLUSIONS: Collectively, our data demonstrate significant spatiotemporal inflammatory and fibrotic differences in human capsule tissue surrounding breast implants, and corresponding oxidative changes to the breast implant surface. Notably, we show that the posterior surface of the implant adopts an increasingly inflammatory phenotype over time and corresponds with increased oxidation of the breast implant surface. This chronic inflammatory environment could contribute to pathologic sequelae such as development of capsular contracture, BIA-ALCL and SCC. The corresponding increased device oxidation could increase risk of implant rupture or gel bleed. This knowledge could be applied to target the posterior peri-prosthetic environment to reduce patient morbidity associated with breast implant surgery.