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

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.