Exosome-Laden 3D Composite Mesh Attenuates Stress Concentration and Promotes Collagen Regeneration toward Pelvic Organ Prolapse Repair.

Pelvic organ prolapse is a prevalent condition that impairs the quality of life in middle-aged and elderly women. Traditional polypropylene (PP) surgical meshes often lead to long-term complications due to mechanical mismatch and biological inertness, manifesting as stress concentration and chronic inflammation. To concurrently address these dual challenges, this study designed and fabricated a multifunctional composite mesh. The mesh incorporates a clinical-grade PP base for mechanical support, integrated with a three-dimensional printed polycaprolactone (PCL) biomimetic network modified by quaternized chitosan (QCS). Human umbilical cord mesenchymal stem cell-derived exosomes (Exos) were further loaded onto this network via electrostatic adsorption. The PP/PCL/QCS composite mesh demonstrated structural integrity and stable degradation. Finite element analysis verified its unique stress-buffering and redistribution capability, which effectively mitigates interfacial stress concentration. Biologically, the PP/PCL/QCS/Exos mesh promoted cell proliferation and adhesion in vitro and showed good biocompatibility in vivo. It actively modulated the repair microenvironment, leading to a rapidly resolved inflammatory response, reduced macrophage infiltration, enhanced myofibroblast activation, and orderly collagen remodeling with a significant increase in collagen type III. Transcriptomic analysis revealed that the mesh induces a systemic anti-inflammatory and pro-repair molecular phenotype. In summary, this work achieves a strategic shift from passive support to active regeneration through synergistic mechanical and biological design, offering a promising direction toward next-generation pelvic floor repair.