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

Abstract

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.

Silicone implant surface microtopography modulates inflammation and tissue repair in capsular fibrosis

“…As described previously in ( 13 , 26 ), this study comprised 10 female patients who underwent simultaneous prophylactic bilateral nipple-sparing mastectomy (NSME) and tissue expander-based breast reconstruction ( Figure 1 ). Written informed consent was obtained from all patients after confirming their eligibility based on the in-and exclusion criteria ( Table 1 ).…”

“…Therefore, 14 peripheral blood draws (7 patients x 2 surgeries), 70 WBF samples (7 patients x 5 days post-op x 2 tissue expander types), 28 capsular tissue specimens (7 patients x 5 days post-op x 2 tissue expander types x 2 sampling locations) and 14 tissue expander surface strips (7 patients x 2 expanders) were evaluated. For a detailed description of the study population see Schoberleitner et al., 2023 ( 13 , 26 ).…”

“…The inflatable tissue expanders were exchanged for definite implants in a second surgery, 6 to 8 months post-implantation. For detailed description of the study design see Schoberleitner et al., 2023 ( 13 , 26 ).…”

“…Patients exhibiting pronounced fibrotic reactions to silicone implants often exhibit elevated serum concentrations of these proteins on implant surfaces, potentially impacting immune responses and fibrosis development ( 11 , 12 ). Utilizing advanced proteomic techniques, comprehensive protein profiles in the acute wound post-implantation have been identified, exposing inflammation and tissue turnover dysregulation, distinct from plasma, with observed time-dependent variations persisting over several months ( 13 ).…”

Phosphorylation of the compartmentalized PKA substrate TAF15 regulates RNA–protein interactions

“…The remaining 80% of the sample were subjected to on-bead tryptic digestion followed by phospho-peptide enrichment using titanium dioxide, prior to LC–MS/MS measurements as described in [ 39 ]. Raw MS data was processed and analysed as described in [ 40 ]. MS measurements were perform in a Q Exactive HF mass spectrometer (Thermo Scientific, USA).…”