Abstract—Despite their great potential in regenerative medicine
applications, stem cells (especially pluripotent ones) currently show
a limited clinical success, partly due to a lack of biological knowledge,
but also due to a lack of specific and advanced technological
instruments able to overcome the current boundaries of stem cell
functional maturation and safe/effective therapeutic delivery. This
paper aims at describing recent insights, current limitations, and
future horizons related to therapeutic stem cells, by analyzing the
potential of different bioengineering disciplines in bringing stem
cells toward a safe clinical use. First, we clarify how and why stem
cells should be properly engineered and which could be in a near
future the challenges and the benefits connected with this process.
Second, we identify different routes toward stem cell differentiation
and functional maturation, relying on chemical, mechanical,
topographical, and direct/indirect physical stimulation. Third, we
highlight how multiscale modeling could strongly support and optimize
stem cell engineering. Finally, we focus on future robotic
tools that could provide an added value to the extent of translating
basic biological knowledge into clinical applications, by developing
ad hoc enabling technologies for stem cell delivery and control