FAK‐Targeting Microneedle Patch Promotes Uterine Regenerative Repair and Restores Reproductive Function Post‐Cesarean Section Via Inhibiting Mechanotransduction
Abstract
Uterine scarring after cesarean section is a major cause of secondary infertility and uterine rupture, and its formation is closely associated with disruption of the mechanical microenvironment at incision sites, yet its mechanobiological basis and effective mechano‐regulatory therapies remain poorly defined. We identify focal adhesion kinase (FAK)‐mediated mechanotransduction as a key driver of post‐cesarean uterine scar formation. To target this process, we developed FAK‐PTC‐Lipo@MN, a biodegradable microneedle patch composed of gelatin methacryloyl (GelMA) and ε‐poly‐L‐lysine‐glycidyl methacrylate (EPLGMA), enabling sustained local delivery of FAK‐PROTAC‐loaded liposomes. In a rat cesarean‐section model, FAK‐PTC‐Lipo@MN reduced inflammatory infiltration, collagen deposition, myometrial thickening, and tissue stiffness, thereby suppressing uterine scar formation. Transcriptomic analysis further showed a shift of uterine repair mode from fibrotic toward regenerative repair, with activation of Wnt/Notch‐related pathways and downregulation of ECM‐associated fibrotic signaling. Functionally, FAK‐PTC‐Lipo@MN promoted uterine functional recovery and improved key reproductive outcomes (e.g., conception time, fetal number, and fetal weight) after cesarean section. Mechanistically, released FAK‐PTC‐Lipo induced FAK degradation and inhibited its activation, thereby reducing F‐actin polymerization, cell traction forces, ECM remodeling and tension, and N‐cadherin‐dependent fibroblast…
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