MICROPATTERNED POLYMER STRUCTURES FOR CELL AND TISSUE ENGINEERING - Biologically-Responsive Hybrid Biomaterials - page 98

PDMS [41] and parylene-C [45, 88] were used to pattern cells on a variety of
substrates. Furthermore, patterned co-cultures have been generated by changing
the surface properties from cell repulsive to cell-adhesive by electroactive and
thermally responsive polymers [89, 90], magnetic forces [91], oxygen plasma
treatment [85]. Some types of microfluidic systems enable novel approaches for
generating co-culture cellular constructs [92]. These approaches use the ability to
produce robust, patterned networks of microchannels for specific cell types,
followed by disassembly of the construct, realignment with a different
superimposed channel network, and culturing of another cell type.
For the simple and reproducible fabrication methods, layer-by-layer
deposition is used for coculture system with specialized materials and extensive
expertise. Khademhosseini et al. [86] demonstrated a moulding-assisted layer-
by-layer deposition of ionic biopolymers of HA (negatively charged) and poly-L-
lysine (PLL) (positively charged). In this method, micropatterns of non-
biofouling HA were used to immobilize one cell type and ionic adsorption of
PLL to HA patterns was used to switch the HA surfaces from cell repulsive to
adherent, thereby facilitating the adhesion of a second cell type. This simple
moulding-assisted layer-by-layer deposition approach is a valuable tool to
control cell-cell interactions, maintain cells in culture, and engineer organs for
tissue engineering [86, 92].
As a coculture model, liver cell cocultures have been examined to achieve
physiologically significant functions of hepatocyte. A challenge in liver tissue
engineering using coculture system is to maintain cell anchorage environment
and to identify essential environmental signals required to maintain hepatic
functions for long periods [93]. The unique property of primary hepatocytes is a
higher selectivity in their cell attachment and spreading on tissue culture
substrate and collagen than that of many other cell types. Hepatocyte functions
are enhanced when co-cultured with fibroblasts, endothelial cells, stellate cells,
and liver epithelial cells [84, 94-98], whereas isolated cells de-differentiate and
lose their hepato-specific function. Moreover, microfabricated substrates can be
used to induce variations in the degree of cell-cell interactions. First, Bhatia
et al. [83] developed a patterned co-culture system of primary hepatocytes
using photolithography. This method was effective in controlling cell contact
and adhesion on the collagen patterned surface. As a more biocompatible
technique, µCP-based methods were used to overcome some drawbacks of
photolithography process [24, 99, 100]. A more dynamic, 3D microfabricated
interdigitating system to control various cell-cell interactions has recently been
demonstrated by Bhatia and coworkers [6, 87]. Their system employed a
microfabricated silicon platform with moving parts or dielectrophoresis (DEP) to