MICROPATTERNED POLYMER STRUCTURES FOR CELL AND TISSUE ENGINEERING - Biologically-Responsive Hybrid Biomaterials - page 94

murine embryonic stem cells (ES) in culture with various secondary cell types,
suggesting that dynamic co-cultures generated by using parylene-C stencils may
be applicable in studying the role of cellular interactions in ES cell
differentiation (Fig. 2C).
2.3. Microfluidic patterning
Microfluidic patterning provides tools to spatially control cells and materials
with appropriately designed configurations. This method uses an elastomeric
microchannel as a guide to pattern polymers, proteins, and cells onto selected
regions [15, 24, 26, 32, 42, 47-49]. The major advantage of microfluidic
patterning is its straightforward fabrication process and generation of patterns
by restricting fluid flow to the desired regions of a substrate. For example, Kim
et al. [50] presented micromolded polymer patterns by allowing a low-velocity
polymer precursor to fill the microchannels spontaneously by capillary action,
namely micromolding in capillaries (MIMIC). Using this method, deeper and
wider microchannels can be generated by pressure-driven flow over large areas.
Most of the microchannel systems have been fabricated using PDMS polymer
due to the easy handling. Inside the microchannels fabricated with PDMS, fluids
are blocked from wetting the substrate in the areas where the PDMS contacts the
surface due to a unique property of PDMS, allowing for a highly conformal
contact. Fluid can be either cured into a solid itself or used to remove underlying
material depending on its composition. Although this approach can be used for
short-term biological control and template-based patterning, it can be merely
applied to a few, metabolically slow cell types, because the flow must be
arrested, while the energy-consuming processes of anchorage and spreading take
place [51].
Using microfluidic patterning, proteins and cells can be immobilized and
delivered selectively to desired areas of a substrate. Takayama et al. presented
microfluidic cell patterning techniques using multiple laminar flow of liquids in
capillary systems, controlling the characteristics of the surface for the selective
cell adhesion (Fig. 3A) [47] or allowing partial treatment of single cells with
pharmacological inhibitor (Fig. 3B) [52]. Ten et al. [53] presented that
hierarchical multi-layered microstructure of cells and biopolymer, such as
collagen or collagen-chitosan matrix, can be formed using microchannels.
Hydrogels can be fabricated with control over the spatial properties of the
materials by embedding a gradient of functional materials, such as RGD peptide,
directly into the material for cell and tissue engineering applications (Fig. 3C)
[54]. Khademhosseini et al. [55] demonstrated an approach to fabricate