Hydrogel-Based Microfluidic Cell Culture 93
Figure 5.3. Overview of hydrogels used for 3-D cell entrapment.
14
For color reference, see
page 261.
Tissue scaffold materials include ceramics, polymers, and composites, but the
majority of matrices are polymeric (Fig. 5.3). Synthetic polymers include polyg-
lycolic acid (PGA), polylactic acid (PLA), polyethylene glycol (PEG), polyvinyl
alcohol (PVA), and many others. Natural polymers include collagen, gelatin,
chitosan, hyaluronic acid, and alginate. Hydrogels are hydrophilic polymer
networks which swell with water.
21
The polymer chains may be crosslinked via
covalent chemical bonds, ionic interactions, or physical bonds. Collagen, agarose,
alginate, PVA, and PEG are all examples of hydrogels.
Hydrogels that undergo gentle gelation processes, which will minimally affect
the entrapped cells, are desired for cell immobilization.
22
Gelation can occur
through chemical crosslinking, ionic crosslinking, or thermal phase change.
5.2.1 Naturally Derived Hydrogels
In tissue engineering, the most commonly used natural hydrogels include
collagen, Matrigel, and alginate.
23
Matrigel is a mixture of proteins extracted from mouse tumor cells.
2
Matrigel
solidifies above 4
C. The chilled liquid is often coated onto plastic tissue culture
dishes, and incubated at 37
C to form a thin gel film. Cells can be cultured on
the gel surface, or their migration behavior into thick gel films can be studied.
Alternatively, cells can be directly mixed into the chilled liquid, which forms a gel
with embedded cells upon incubation at warm temperature. Matrigel has been
widely used in angiogenesis assays, in which endothelial cells are cultured on the
gel.
Matrigel contains many proteins, including laminin, and collagen IV, as well
as heparan sulfate proteoglycans, many other proteins in low concentrations,
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