ENGINEERING ARTIFICIAL STEM CELL NICHES - Biologically-Responsive Hybrid Biomaterials - page 290

extracellular matrix with relatively high affinity, one open challenge in this area
will be to tether 3D gradients to hydrogel networks.
2.6. Mimicking the spatial 3D niche heterogeneity
How do stem cells sense and respond to spatially heterogeneous 3D
microenvironments? As described previously, many in vivo stem cell
microenvironments are 'polarized' structures, exposing individual stem cells to
differential niche components. A case in point is the niche of the muscle
(satellite) stem cell, which is located between the muscle fiber membrane and the
surrounding basal lamina. An ideal 3D in vitro model of a stem cell niche would
allow recapitulating such complex architectures and manipulate it at a desired
time during an experiment, for example to address the question whether
microenvironmental polarity dictates the symmetry of stem cell division. Clever
hydrogel engineering tricks based on photochemistry now promise to do that,
with impressive precision and control over the dynamics as well (Figure 6). 89,90,91
For example, using photopolymerized PEG hydrogels, Anseth and colleagues
have synthesized photo-labile building blocks that can be cleaved by a controlled
light beam to locally modulate biophysical and biochemical gel properties at a
given time point. MSCs were shown to respond to locally induced network
changes in stiffness and cell adhesion properties: in a densely crosslinked gel, the
decrease in crosslinking density obtained via cleavage of the photolabile chain
backbone induced a significant morphological change in the encapsulated stem
cells. Moreover, the controlled manipulation of cell-adhesive peptide ligand
concentration in the PEG gel led to inducible changes in chondrocytic
differentiation. These new methods of locally manipulating the 3D
microenvironment using light will surely be powerful to explore a wealth of
question in stem cell biology.
2.7. From artificial niches to 3D in vitro 'tissues'
Knowing how stem cell fate is controlled by niche signals should be a
cornerstone in starting to build tissues outside of an organism. The 3D
approaches discussed above serve as powerful model systems to elucidate
extrinsic stem cell regulation, but they would not be appropriate to start re-
constructing large-scale tissue models using stem cells and biomaterials as
building blocks. 'Bioprinting' could perhaps be the technology of choice to
facilitate such difficult endeavors. Indeed, bioprinting technologies are