From silicone gel bleed chemistry to skeletal muscle and lipid alterations: clinical and in vitro evidence
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Musculoskeletal symptoms are frequently reported following silicone breast implantation. However, the biological mechanisms linking implant-derived silicone exposure to skeletal muscle alterations remain poorly understood, partly because the biological effects of silicone have long been debated in the context of its biocompatibility. Here, we chemically characterized the low-molecular-weight fraction of the breast implant silicone exposome, readily released from implant gel through “gel bleed”, and investigated its potential biological consequences using an integrated approach combining analytical chemistry, clinical transcriptomics and histology, and controlled in vitro muscle experiments. Transcriptomic analyses of periprosthetic tissues associated with silicone implant rupture revealed unexpected myogenic and neuromuscular signatures in tissue conventionally regarded as predominantly fibrous, together with alterations in lipid metabolism and transport. These findings were supported by histological evidence of close interactions between periprosthetic tissue and skeletal muscle. Chemical analysis of the implant-gel extract detected linear siloxane L2 and cyclic siloxanes D3–D8, with tentative assignment of D9. In vitro , C2C12 cells exposed to the implant-gel extract showed up to 30% reduced viability and decreased expression of key neuromyogenic genes. Together, these findings provide convergent chemical, clinical, and experimental evidence that low-molecular-weight constituents of the breast implant silicone exposome may constitute a biologically active exposure capable of affecting skeletal muscle. The associated alterations in lipid metabolism and transport further provide a mechanistic framework for investigating the cellular handling and potential tissue distribution of hydrophobic silicone-derived species. These findings position silicone gel bleed as a biologically relevant source of chemical exposure rather than solely a material-integrity phenomenon.
Highlights
-
Histological analysis revealed skeletal muscle areas closely integrated with periprosthetic fibrotic tissue.
-
Patient-derived RNA sequencing reveals that silicone exposure exerts biological effects beyond inflammation, directly impacting both myogenic and lipid pathways.
-
A gel implant-conditioned medium, chemically characterized by GPC and GC-MS, was used as an in vitro silicone exposure model and revealed a heterogeneous LMWS profile comprising L2 and cyclic siloxanes D3–D8, with D9 tentatively identified.
-
The viability of differentiating muscle cells in vitro is altered by up to 30% by implant-derived LMWS.
-
Silicone exposure induces muscle transcriptomic alterations in vitro , recapitulating key RNA-sequencing signatures observed in patient tissues, even in the absence of an inflammatory environment
-
RNA-seq analysis uncovered dysregulation of lipid metabolism genes, including key lipoprotein markers, suggesting that silicone exposure may disrupt endogenous lipid transport pathways in periprosthetic tissues.
