• Nanotopography of electrospun PLLA membranes promotes osteogenic differentiation of hBMSCs by modulating chromatin accessibility of the YBX1 gene promoter, leading to its upregulation.
• ATAC-seq and RNA-seq reveal that open chromatin regions (OCRs) are key mediators of topographical cues in stem cell differentiation.
• Lentiviral knockdown of YBX1 reverses the osteogenic effects induced by nanotopography, confirming its crucial role in mechanotransduction.
• These findings provide a mechanistic basis for designing biomaterials with tailored nanotopography to direct stem cell fate in regenerative medicine.