Biomedical Engineering Reference
In-Depth Information
concentrationofboththealginateandthecross-linkingagent,
33
and
the type of cross-linking cations (Mg
2
+
<
Ca
2
+
<
Zn
2
+
<
Sr
2
+
<
Ba
2
+
).
35
Fortissueengineeringapplications,cellsaretypicallymixedwith
the alginate solution and cross-linked in a solution of
∼
100 mM
CaCl
2
. One interesting aspect of alginate is that it can be easily dis-
solved using a calcium chelator, such as sodium citrate, and the
cells with associated matrix can be recovered and used to form
constructs.
36
Alginate has shown excellent ability to retain the typ-
ical spherical chondrocyte phenotype and also to serve as a better
model system of chondrogenesis than micromass pellets.
38
Alginate
also can be functionalized with peptides, such as arginine-glycine-
aspartic acid (RGD), to affect cell behavior, through carbodiimide
chemistry.
39
AlginatecanbeformedintohydrogeldisksbymixingwithCaSO
4
and cross-linking in a mold
40
, partially dissolving in sodium citrate,
and then combining gels by further cross-linking with CaCl
2
to form
layered alginate constructs (Fig. 36.3c).
41
The shear stiffness and
toughness of the layered constructs generally increased with time
and were similar to or greater than single-layer constructs, indicat-
ing good integration using this method. Alginate can also be printed
into arbitrary geometries using direct free-form fabrication tech-
niquesand couldthus beused to create zonalconstructs.
42
Alternatively, alginate can be used to preculture zonal chon-
drocytes, and these cells with an associated matrix can then be
used to form zonal constructs that do not contain exogenous matri-
ces (e.g., alginate). These constructs maintained stratification and
Figure 36.3.
(a) Alginate is a linear polysaccharide composed of block
repeatsof(1,4)-linked
β
-D-mannuronicacid(M)and
α
-L-guluronicacid(G)
monomers; (b) alginate cross-links in the presence of divalent cations, (c)
maintains viable chondrocytes with a round morphology (confocal image
at 8 weeks), and (d) can be formed into layered structures (dyed here with
food color).
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