A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. Recently, the authors have shown that two types of slightly disordered arrays of nanopits stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. In this article, they aim at optimizing the topographic parameters to stimulate MSCs to form bone cells. They have developed a high-speed electron beam technique to pattern 1 cm(2) areas with 10(9) dots. In three steps, they (1) systematically changed the degree of disorder from +/- 30 to 150 nm from a perfect square arrangement with a 300 nm pitch, (2) changed the pit diameter from 50 to 193 nm, and (3) explored the importance of pits versus pillars. They found that arrays of pillars 35 nm tall with a diameter of 193 nm and a disorder of +/- 30 nm provided the optimal conditions for stimulating MSCs to form bone cells.