MICROPATTERNED POLYMER STRUCTURES FOR CELL AND TISSUE ENGINEERING - Biologically-Responsive Hybrid Biomaterials - page 97

demonstrated that a capillary force-induced cell alignment and elongation
extended from contact guidance using anisotropic roughness with cell behavior
[58]. Ball et al. [59] showed that osteoblast-like cells respond differently to
similar surface roughness with ordered (aligned grooves) and disordered
(random) features. On ordered pillars and gratings, despite having similar surface
roughness, cells responded differently. Crouch et al. [73] showed the anisotropic
behaviors of cell adhesion to well controlled gratings with various widths and
depths to investigate topographic effects on cell behaviors. The aspect ratio of
the gratings is a useful factor to characterize topographic effects on cell
alignment and elongation. Human foreskin fibroblast (HFF) cells and smooth
muscle cells were aligned if the angle of their long axis with respect to the
grating direction is ±15°; while endothelial cells and human colonic epithelial
(HCEC) cells were aligned with angle of ±20° and ±10°, respectively [58, 65,
67, 68, 73-77].
To generate microtopographic patterns, capillary force lithography (CFL)
techniques offer a number of advantages in fabricating geometry-controllable,
robust microstructures over a large area [78, 79]. Capillarity is a simple and
useful concept by one step patterning process with polymer materials and
generated when a liquid wets a capillary tube and moves with lowering of the
free energy. A recent study demonstrated that microtextured substrates with
variable local density and anisotropy fabricated by CFL-based molding
techniques can guide the organization and migration of fibroblasts in spatially
desirable locations [80].
3. Microengineering of Cellular Interaction by Polymeric Biomaterials
3.1. Patterned co-cultures for controlling cell-cell interactions
The generation of co-culture system is crucial to understanding intricate cellular
mechanisms and cell-cell interactions for cell and tissue engineering. An
important aspect in tissue formation and function is the interaction between
multiple types of cells within the tissue [81]. Despite this need, most commonly
used in vitro studies lack the multicellular functionality and the organization that
parallels the in vivo cellular microenvironment. In traditional co-culture
techniques, multiple cells were seeded randomly and thus it is difficult to control
the degree of various homotypic and heterotypic cell-cell interactions. To
overcome this limitation, patterned co-cultures have been developed using
various microfabrication technologies, including photolithography, microfluidics,
membrane lift-off, switchable surfaces, [6, 16, 26, 47, 82-88]. Briefly, stencils of