ENGINEERING ARTIFICIAL STEM CELL NICHES - Biologically-Responsive Hybrid Biomaterials - page 291

increasingly being scrutinized to try to recreate the 3D spatial organization of
tissues (e.g. 92,93,94 ) In bioprinting, custom-designed inkjet printers are applied to
deposit, in a controlled layer-by-layer fashion, cells and biomaterials in nearly
picoliter-sized droplets at a rate of tens of thousands per second. Upon deposition
on a substrate, these droplets can be polymerized to form a solid gel that could
encapsulate stem cells or contain biomolecules with locally modular
composition. Although the bioprinting field has arguably had little impact on
stem cell biology so far, the already obtained results look promising. Lee and
colleagues for example have presented an approach to pattern in 3D viable
constructs of neurons and astrocytes in multilayered collagen. Clearly, if
bioprinting were to become more robust and a suitable 'bioink' available (which
is arguably not the case), it would represent a tremendous step forward in
realizing the long-standing dream of tissue-engineers, that is, the formation of
functional tissues outside the human body.
3. Conclusions and Outlook
The merger of concepts and know-how from biomaterials science,
microfabrication technology and stem cell biology has already resulted in novel
experimental tools that begin to impact stem cell biology. A simplification of the
niche complexity, combined with advanced imaging approaches on live stem
cells, allows the investigation of the role of specific niche components and the
3D niche architecture in regulating fundamental behaviors such as mechanisms
of cell division, self-renewal and differentiation. Applied in vitro, this may well
lead to the generation of adequate numbers of stem cells and the ability to
precisely control their differentiation in order to maximize their clinical utility as
cell-based therapeutics for tissue regeneration.
However, it can be expected that many in vitro findings will result in new
approaches to manipulate stem cells in vivo as well. For example, biomaterials
concepts could be devised to locally and specifically deliver bioactive niche
components or inhibitory/stimulatory molecules or drugs to a particular stem cell
niche, to increase stem cell numbers for example. This could be realized either
from the 'bulk' (solid) phase (Fig. 7a) , by forming a drug/biomolecule-releasing
scaffold in close proximity to a stem cell niche, or via targeted delivery of
soluble micro- or nanoparticles (Fig. 7b) . 95 Biofunctional polymer particles can
now be engineered to render them efficient for such applications, as they can be
functionalized to confer molecular targeting, environmental responsiveness,
controlled drug release or designed cell uptake as demonstrated by Hubbell and