A Novel Knitted Silk Mesh Orchestrates Macrophage M2 Polarization and Angiogenesis for Functional Pelvic Floor Reconstruction.

Abstract

Pelvic organ prolapse (POP), a prevalent gynecological disorder affecting 41-50% of women globally, causes significant quality-of-life deterioration. While nondegradable polypropylene mesh (PPM) reduces surgical recurrence rates, its utility is restricted by complications including erosion, infection, and chronic inflammation. Strategic modulation of inflammatory homeostasis and neovascularization has emerged as a critical pathway to mitigate these sequelae. Here, we engineered a microporous and ultralightweight knitted silk mesh (KSM) from biodegradable <i>Bombyx mori</i> fibroin. In vitro characterization demonstrated KSM's mechanical parity with PPM, alongside superior water absorption capacity. Human vaginal fibroblasts exhibited enhanced proliferation on KSM. In vivo evaluation in a rat abdominal defect model revealed KSM's reduced adhesion severity, increase in collagen III deposition, M2-dominant macrophage polarization, and elevated angiogenesis. RNA sequencing identified fibronectin (FN) as the hub regulator of mechanotransduction, with subsequent validation of the FN-integrin β1-FAK signaling axis driving vascular endothelial cell migration. These findings establish KSM's dual capacity to provide biomechanically compliant support while orchestrating immunomodulatory and angiogenic microenvironments, addressing the critical unmet need for functional pelvic floor reconstruction. The mechanistic insights into FN-mediated mechanobiology offer novel therapeutic paradigms for regenerative material design.