Silicone substrate topography modulates fibroblast-to-myofibroblast transition through Filamin A-mediated TGFβ/Smad signaling pathway

Abstract

• Microgroove surface topography of PDMS inhibits fibroblast-myofibroblast transition by modulating Filamin A and TGFβ/Smad signaling pathways. • Silicone Substrate Topography reduces fibrosis markers, including Filamin A, TGFβ1, Smad2/3, and α-SMA, suggesting potential for preventing capsular contracture • Multi-omics analysis identifies key proteins and metabolites involved in cytoskeletal remodeling and collagen synthesis, supporting optimized material design for soft tissue repair. Capsular contracture, a prevalent complication of polydimethylsiloxane (PDMS) implants, severely compromises patients’ quality of life. While surface morphology is recognized as a PDMS-related factor influencing capsular contracture, the precise mechanism by which this physical alteration affects intracellular signaling remains unclear. In this study, we developed smooth PDMS and bionic microgrooved surfaces PDMS. Through in vitro cell experiments, in vivo implantation, and multi-omics analysis, we investigated how surface microstructures modulate fibroblast transformation. Results demonstrated that microgrooved PDMS significantly inhibited fibroblast-mediated transformation (FMT) and downregulated expression of filamentous protein A (FLNA), TGFβ1, Smad2/3, and α-SMA. These findings indicate that PDMS exerts anti-fibrotic effects by regulating the FLNA-mediated TGFβ/Smad signaling pathway, thereby disrupting cytoskeletal remodeling and extracellular matrix accumulation. Multi-omics analysis further identified differential expression proteins and metabolites involved in cytoskeletal dynamics, collagen synthesis, and metabolic pathways. In conclusion, the PDMS surface substrate morphology critically regulates fibroblast transformation by modulating the cytoskeleton and signaling pathways, providing a theoretical basis for optimizing the design of soft tissue repair materials.