MICROPATTERNED POLYMER STRUCTURES FOR CELL AND TISSUE ENGINEERING - Biologically-Responsive Hybrid Biomaterials - page 99

bring cells in close proximity to each other and could be used for improved
dynamic and temporal regulation of cellular structures.
Khademhosseini et al. [101] presented a technique to culture human
embryonic stem (hES) cells with controlled size of cluster for maintenance and
subsequent differentiation. To maintain their undifferentiated state, hES cells are
commonly cultured as cell cluster with feeder layer of murine embryonic
fibroblasts (MEFs). Therefore, an approach controlling the size of hES cell
clusters in co-culture with MEF feeder cells using micropatterning techniques
may be beneficial for controlling the homogeneity of the cultures. The results of
co-cultures of MEFs and hES cells generated on microwell-patterned PDMS
surfaces reveals that cells are maintained in an undifferentiated condition
homogeneously. In addition, the cell clusters can be restored to generate
homogenous cell aggregates for the research of stem cell differentiation.
3.2. Microfabricated 3D polymeric scaffolds for tissue engineering
Living tissues are composed of highly organized ensembles of various cell types
embedded in ECM with complex 3D topographical features [102, 103]. In native
tissue, the ECM is composed of specific proteins, signaling molecules, growth
factors, and many tropic agents and possesses hierarchically arranged topography
that influences various cellular functions, such as adhesion, proliferation,
migration, and differentiation [9, 10, 13-17, 82, 104-108]. Therefore, it is
essential to generate defined scaffolds serving to mimic the structure and
functions of ECM and guide the dynamic organization of cells into tissues.
Tissue engineering has emerged to replace a wide range of dysfunctional tissues
and regenerate tissues using cells, scaffolds, and growth factors alone or in
combination.
Cells on 3D architectures with a complex set of mechanical forces and
biochemical signals behave similar with in vivo conditions that cannot be
replicated in standard 2D cell culture. For instance, breast cancer cells cultured in
3D in the presence of antibodies for specific integrin receptors become non-
cancerous as opposed to 2D culture systems [109]. A 3D self assembling peptide
scaffold has been shown to promote tissue-like function and further to provide a
microenvironment capable of differentiating stem cells into mature liver cells
acquiring a spheroidal morphology [110]. This matrix has also been applied to
neural cell cultures and numerous other cell types providing a better
physiological approach [111]. Also, many approaches on hepatic-tissue
engineering involve seeding isolated hepatocytes on surfaces, biodegradable
polymer films [112], three dimensional porous polymeric scaffolds [113-115],