Stress-Induced Vaginal Remodeling: Fibroblast Mechanotransduction and Mesh Complications

Pelvic organ prolapse (POP) repair using synthetic mesh introduces mechanical mismatches that significantly influence fibroblast behavior. As the primary mechanosensitive cells in vaginal connective tissue, fibroblasts respond to extracellular stiffness via mechanotransduction pathways, such as focal adhesions (FAs), transforming growth factor β (TGF-β) signaling, and others. These pathways regulate key cellular responses, including proliferation, apoptosis, and differentiation into myofibroblasts. While transient myofibroblast activation is essential for normal wound healing, sustained activation driven by mesh can result in complications-primarily pain and fibrosis. This review highlights the molecular and mechanical mechanisms underlying fibroblast-to-myofibroblast transition (FMT), with a focus on integrin-mediated adhesion complexes and cytoskeletal signaling. It also explores how mesh architecture and local mechanical cues contribute to pathological tissue remodeling in POP. Understanding these processes can inform the design of biomechanically compatible meshes and targeted therapeutics such as ROCK or YAP inhibitors to mitigate adverse fibroblast responses and improve surgical outcomes.