Next generation tissue engineering and regenerative medicine solutions will include implantable materials that will actively participate in tissue formation by programming multiple cell-instructive cues into the biomaterial itself.[1-6]. My objective is to develop multifunctional biomaterials that can release growth factors, present ligands, and deliver physical cues in order to sequentially recruit, organize and differentiate stem cell populations.[5-8] Extreme micro- and nanotopographies, such as dense arrays of high aspect ratio pillars, can provide a basis for several levels of functionality on biomaterial surfaces. Combinations of the geometry, distribution and stiffness of nanopillars can be leveraged to elicit defined changes in cell shape and differentiation. We fabricate these structures with nanoscale precision by photolithography/DRIE and replicate them into polymers by mold-casting to provide a diversity of chemical and physical properties. Current efforts are focused on scrutinizing the influence of various geometries and densities of ordered NP arrays on the morphology of pluripotent cells and lineage specification of human mesenchymal stem cells. The development of ‘smart’ materials and their routine application in medical devices will benefit greatly from the identification of topographies that elicit specific cellular responses, understanding how cells interpret these topographic cues, and designing new strategies to couple topography with chemical, mechanical and other vital cell stimuli.