• • Electrospun PLLA membranes with random fiber arrangements (nanotopography) promote osteogenic differentiation of hBMSCs, as evidenced by increased chromatin accessibility at the YBX1 promoter and upregulated YBX1 expression, confirmed by ATAC-seq and RNA-seq.
• • Lentiviral knockdown of YBX1 reverses the osteogenic effects induced by nanotopography, demonstrating that YBX1 is a critical mediator of topography-induced osteogenesis.
• • YBX1 influences chromatin accessibility and remodeling; ATAC-seq of hepatic-specific YBX1-OE mice showed increased chromatin accessibility in pathways related to ECM accumulation, lipid purine metabolism, and oxytocin signaling.
• • The findings suggest that nanotopographical cues can be harnessed to direct stem cell fate, offering a controlled and predictable means for tissue regeneration, with potential applications in regenerative medicine and tissue engineering.