Targeting the Spata13-TGFβRI interaction inhibits infection-driven capsular contracture via suppression of fibroblast...

Capsular contracture, a common complication following breast implant surgery, is driven by fibroblast-to-myofibroblast transition and excessive collagen deposition. Although bacterial biofilm and TGF-β signaling are implicated, the molecular mechanisms linking infection to fibrosis remain unclear. Using in vitro fibroblast models and in vivo rat capsular contracture assays, we combine transcriptomics, protein interaction analysis, and targeted mutagenesis to identify Spata13 as a critical mediator of TGF-β/Smad signaling. Functional assays assess collagen synthesis (hydroxyproline content), fibroblast proliferation (CCK-8), and myofibroblast markers (α-SMA). A competitive peptide (PT637) is designed to disrupt Spata13-TGFβRI binding. Staphylococcus epidermidis biofilm synergizes with silicone implants to upregulate Spata13, activates TGF-β/Smad signaling, and promotes fibroblast activation. Spata13 binds to TGF-β receptor I (TGFβRI) via Ser637, and its knockdown suppresses α-SMA expression and collagen deposition. The TGFβRI inhibitor LY2157299 attenuates fibrosis in vivo. Strikingly, PT637 disrupts the Spata13-TGFβRI interaction and reduces both fibrosis markers and capsular thickness in biofilm-challenged rats. We define Spata13 as a novel regulator of infection-associated fibrosis and demonstrate that targeted disruption of Spata13-TGFβRI binding by PT637 offers a precision therapeutic strategy for capsular contracture.