94 M. C. W. Chen and K. C. Cheung
and growth factors. Not all of its components have been identified. For many
applications, the use of a scaffold material that more closely mimics the natural cell
environment would be more appropriate. In addition, the use of animal-derived
materials may be controversial in some tissue engineering applications.
5.2.2 Alginate
Alginates are naturally derived polysaccharide polymers isolated from seaweed.
They have been used as food stabilizers and thickeners, and as drug release materi-
als. Alginates are block copolymers consisting of (1-4)-linked β-
D-mannuronic acid
(M units) and α-
L-guluronic acid (G units) (Fig. 5.4). The mechanical properties of
the hydrogel depend on the ratio of the M to G units. Divalent cations such as Ca
2+
or Ba
2+
bind between the G-blocks of adjacent alginate chains, giving ionic cross-
linking.
24
A higher M-unit content gives the polymer chains more flexibility in
solution. The gel can be stiffened by increasing the G-unit content or by increasing
the length of the G-unit blocks.
25
Alginate hydrogels have been extensively used in cell encapsulation. Islet
transplantation has been investigated as an approach for treatment of insulin-
dependent diabetes,
26
and hepatocyte encapsulation has been investigated in
the development of bioartificial livers.
27
For islet transplantation, the alginate
microcapsule provides immunoisolation for the transplanted xenogeneic (cross-
species) cells. Calcium alginate capsules have already demonstrated long term
biocompatibility in animal studies and clinical trials
28
(Fig. 5.5). Since sodium
ions in the physiological environment will exchange with the divalent cations in
the alginate, the gels can weaken mechanically over time after implantation. One
approach used to increase the mechanical strength of cell capsules has been to coat
the capsules with a layer of poly-
L-lysine. Alginate gel beads can be produced by
using a syringe pump to push droplets of an alginate-cell suspension into a bath
of calcium chloride. In addition, coaxial air jets and electrostatic bead generators
are now commercially available.
Alginates can be modified with cell adhesion ligands to improve cell
attachment.
22
Covalent modification of the carboxylic acid functional groups
2
2
2
+2
2+
22&
2
2+
&22
2
2
2+
D E
Figure 5.4. The monomers of alginate. (a) (1, 4)-linked β-D-mannuronic acid (M).
(b) (1, 4)-linked α-L-guluronic acid (G).
SO13997_text.indd 102SO13997_text.indd 102 26/01/2011 3:50 PM26/01/2011 3:50 PM

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