This study investigates the effect of nanotube dimensions on the fate and behavior of human mesenchymal stem cells (hMSCs). By altering the diameter of titanium oxide (TiO2) nanotubes, the researchers found that small (≈30-nm diameter) nanotubes promoted hMSC adhesion without significant differentiation, while larger (≈70- to 100-nm diameter) nanotubes induced dramatic cell elongation and selective differentiation into osteoblast-like cells. The results suggest that the geometric cues provided by the nanotube dimensions, rather than chemical factors, can control hMSC differentiation. This finding opens up a promising route for using nanotechnology to guide hMSC treatments in orthopedics and other fields. The study also highlights the importance of protein aggregate adhesion and the role of substrate topography in cell behavior, providing insights into the mechanisms underlying stem cell fate determination.This study investigates the effect of nanotube dimensions on the fate and behavior of human mesenchymal stem cells (hMSCs). By altering the diameter of titanium oxide (TiO2) nanotubes, the researchers found that small (≈30-nm diameter) nanotubes promoted hMSC adhesion without significant differentiation, while larger (≈70- to 100-nm diameter) nanotubes induced dramatic cell elongation and selective differentiation into osteoblast-like cells. The results suggest that the geometric cues provided by the nanotube dimensions, rather than chemical factors, can control hMSC differentiation. This finding opens up a promising route for using nanotechnology to guide hMSC treatments in orthopedics and other fields. The study also highlights the importance of protein aggregate adhesion and the role of substrate topography in cell behavior, providing insights into the mechanisms underlying stem cell fate determination.