Macrophage Inflammatory Response to Breast Implant Debris

Introduction: Some “macrotextured” silicone breast implants have been linked with the formation of a rare large cell lymphoma (breast-implant anaplastic large-cell lymphoma (BIA-ALCL)). The formation of silicone wear debris may perpetually provoke the immune response. As cytokines and pro-inflammatory markers accumulate around wear debris particles, reactive oxygen species and continued inflammation may damage increasingly larger areas of tissue. Silicone elastomer particulates and immune cells have been discovered in fibrous capsules retrieved from patients, which supported the long-standing hypothesis that implant wear debris may initiate the inflammatory response.

Materials and

Methods: We have modeled the formation of silicone wear debris using a custom-built linear reciprocating tribometer in the case of a folded implant-implant sliding interface for different implant types, characterized by surface roughness. We engineered particles with controllable stiffnesses to replicate the size and aspect ratio of silicone debris particles to identify particular stiffness ranges that induce macrophage inflammation. Using a bead-based ELISA assay, we characterized the cytokine response due to debris particles of varying stiffness, size, and aspect ratios. We further identified macrophage morphological changes and phagocytosis in response to silicone debris particles with confocal microscopy.

Results, Conclusions, and Discussions: We found that the “macrotextured” silicone implant surface (Ra = 80 ± 10 μm) resulted in higher frictional forces and greater debris formation than the “microtextured” silicone breast implant (Ra = 32 ± 7.0 μm). We uncovered a stiffness dependence of debris particles on inducing macrophage inflammation. Macrophages responded with cytokine inflammation during the phagocytosis of silicone particles of 1 MPa in stiffness, but did not respond to particles on the order of 1 – 10 kPa. Specifically, TNF-α and IL-6 were expressed highly in macrophages treated with debris from the macrotextured implant, but lowly expressed in macrophages treated with debris from the microtextured implant. Additionally, macrophage perimeter drastically decreased as circularity increased after phagocytosis of silicone debris particles. These findings highlight the importance of designing silicone elastomer breast implants with optimal surface texturing to reduce frictional shear stresses and wear debris generation.

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