Biomaterials for MEMS

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).

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