The modulation of skeletal stem cell function through nanoscale topography

Skeletal stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate would have tremendous potential for basic research and clinical therapy. Recent advances in microelectronic engineering techniques have paved the way for the development of nanoscale cellular technologies in medicine and basic science. In particular nanotopographical modification of an orthopedic device may provide valuable stimulation for guiding differentiation and cellular function, presenting specific cues which are more durable than surface chemistry and can be modified in size, shape and density to suit the desired application. Furthermore, due to a continuously advancing state of the art, nanofabrication methods are quickly giving rise to an ability to faithfully produce feature of sub 5 nm, the scale of a single molecule. In this chapter, nanotopography is examined as a means to guide stem cell differentiation, with a particular focus on skeletal (mesenchymal) stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated) and direct (force-mediated) mechanotransduction are discussed, with emphasis on mechanotransduction through focal adhesion complexes and the cytoskeletal network. Finally, the technological advances in nanofabrication of materials and devices with the potential for clinical translation will be addressed.