Quantitative Proteomic Characterization of Foreign Body Response towards Silicone Breast Implants Identifies Chronological Disease-Relevant Biomarker Dynamics

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms towards the foreign material silicone. The aim of this work was to understand the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intraindividual relative quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to the profile wound proteome formed around SMI in the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to a functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation, which were adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by a label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Automated summary

Exaggerated fibrous capsule formation around silicone mammary implants (SMI) is primarily induced by immune mechanisms towards silicone. This study aimed to understand the disease progression from implant insertion and immediate tissue damage response. A proteomic analysis revealed a complex composition of acute wound profile and differential protein expression on the implant surfaces. Dysregulation of signaling pathways involved in inflammation and extracellular matrix turnover was observed. Time-course variations in protein enrichment immediately post-implantation and long-term adsorption of acute wound and fibrosis-associated proteins were identified. The findings propose a potential biomarker panel for early detection and diagnosis of excessive fibrosis in implant encapsulation.