Cells sense and respond to a variety
of physical cues from their
surrounding microenvironment, and these are interpreted through mechanotransductive
processes to inform their behavior. These mechanisms have particular
relevance to stem cells, where control of stem cell proliferation,
potency, and differentiation is key to their successful application
in regenerative medicine. It is increasingly recognized that surface
micro- and nanotopographies influence stem cell behavior and may represent
a powerful tool with which to direct the morphology and fate of stem
cells. Current progress toward this goal has been driven by combined
advances in fabrication technologies and cell biology. Here, the capacity
to generate precisely defined micro- and nanoscale topographies has
facilitated the studies that provide knowledge of the mechanotransducive
processes that govern the cellular response as well as knowledge of
the specific features that can drive cells toward a defined differentiation
outcome. However, the path forward is not fully defined, and the “bumpy
road” that lays ahead must be crossed before the full potential
of these approaches can be fully exploited. This review focuses on
the challenges and opportunities in applying micro- and nanotopographies
to dictate stem cell fate for regenerative medicine. Here, key techniques
used to produce topographic features are reviewed, such as photolithography,
block copolymer lithography, electron beam lithography, nanoimprint
lithography, soft lithography, scanning probe lithography, colloidal
lithography, electrospinning, and surface roughening, alongside their
advantages and disadvantages. The biological impacts of surface topographies
are then discussed, including the current understanding of the mechanotransductive
mechanisms by which these cues are interpreted by the cells, as well
as the specific effects of surface topographies on cell differentiation
and fate. Finally, considerations in translating these technologies
and their future prospects are evaluated.