This paper presents a technique to independently form mechanical topography and surface chemical patterns on polymer cell substrates, and studies the response of osteoblast cells to these surface patterns. The patterns were formed in two separate steps: hot embossing imprint lithography formed the mechanical topography and microcontact printing created the chemical pattern. The resulting substrate had surface features consisting of embossed grooves 4 microm deep and 8 microm wide spaced by 16 microm wide mesas and microcontact printed adhesive lanes 10 microm wide with spacings that ranged from 10 to 100 microm. When presented with either mechanical topography or chemical patterns alone, the cells significantly aligned to the pattern presented. When presented with mechanical topography overlaid with an orthogonal chemical pattern, the cells aligned to the mechanical topography. As the chemical pattern spacing was increased, osteoblasts remained aligned to the mechanical topography. Unlike traditional microfabrication approaches based on photolithography and wet chemistry, the patterning technique presented is compatible with a large number of biomaterials, could form patterns with features much smaller than 1 microm, and is highly scalable to large substrates.