Proteomic Profiling of Breast Implant Capsules: a Novel Approach for Studying Biocompatibility and Capsular Contracture.

Abstract

Background: Standardized molecular methods to assess the host response to breast implants are lacking. Mass spectrometry-based proteomics offers an unbiased approach to characterize the capsule proteome and the foreign-body response.

Objectives: To establish proof-of-concept for deep proteomic profiling of human breast implant capsule tissue and explore the proteomic profile associated with capsular contracture.

Methods: Capsule biopsies were obtained from women with capsular contracture (Baker III/IV, n = 24) and non-contracture controls (Baker I, n = 24). Proteomic profiles were analyzed by liquid chromatography-tandem mass spectrometry with label-free quantification. Differential expression, co-expression network, and functional enrichment analyses were performed, and capsules were additionally scored with a validated histopathological system.

Results: Deep proteomic profiling quantified 7,258 proteins (median 5,879 per sample). Unsupervised analyses separated contracture from control samples without prior grouping information, indicating a distinct contracture-associated proteome (P = 0.001). We identified 77 differentially expressed proteins (31 upregulated, 46 downregulated). Extracellular matrix (ECM) remodeling dominated, with upregulation of MMP9 and inhibitors TIMP1 and TIMP3. A profibrotic TGF-β signature included THBS1, THBS2, periostin, and TGM2, and innate immune activation included MPO, FCGR1A, S100A8, and S100A9. Co-expression network analysis identified a contracture-associated neutrophil degranulation module, and an adaptive immune module linked to implantation time and rupture.

Conclusion: Deep proteomic profiling of human breast implant capsules is feasible and revealed a contracture-associated proteomic phenotype dominated by ECM dysregulation, a profibrotic TGF-beta axis, and innate and adaptive immune activation. These findings provide proof-of-concept for capsule proteomics as a tool to study the host response to breast implants.