In this study, hybrid micropatterned grafts constructed via a combination of microcontact printing and electrospinning techniques process were utilized to investigate the influencing of patterning directions on human mesenchymal stem cells (hMSCs) differentiation to desired phenotypes. We found that the stem cells could align and elongate along the direction of the micropattern where they randomly distributed on non-micropatterned surfaces. Concomitant with patterning effect of component on stem cell alignment, a commensurate increase on the expression of neural lineage commitment markers such as microtubule associated protein 2 (MAP2), Nestin, NeuroD1 and class III β-Tubulin, were revealed from mRNA expression by quantitative Real Time PCR (qRT-PCR) and MAP2 expression by immunostaining. In addition, the effect of electrospun fiber orientation on cell behaviors was further examined. The angle of 45 degree between the direction of micropatterning and orientation of aligned fibers was verified to greatly prompt the outgrowth of filopodia and neurogenesis of hMSCs. This study demonstrates that the significance of hybrid components and electrospun fiber alignment in modulating cellular behaviour and neurogenic lineage commitment of hMSCs, suggesting promising application of porous scaffolds with smart component and topography engineering in clinical regenerative medicine.