FAK-Targeting Microneedle Patch Promotes Uterine Regenerative Repair and Restores Reproductive Function Post-Cesarean Section Via Inhibiting Mechanotransduction

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 collective migration. This study establishes FAK-targeted mechanotherapy as a promising strategy for uterine incision regeneration and reproductive function restoration after cesarean section.