Biomedical Engineering Reference
In-Depth Information
associated with aggrecan and hyaluronic acid to form massive
proteoglycanaggregates.Alsoimportantisthevariationintotalsul-
fated glycosaminoglycan content (low at the surface) and the gradi-
ent of keratan sulfate (low at the surface
24
) and dermatan sulfate
(high at the surface
25
). The extracellular environment established
bytheseglycosaminoglycansislikelycriticalfortheproperfunction
of the resident chondrocytes. Thus, it is not entirely surprising that
hydrogelsbasedoncarbohydrateswithsimilarproperties,primarily
alginateandagarose,aresuccessfulforthemaintenanceofthechon-
drocytephenotypeandinthere-differentiationofchondrocytesthat
have de-differentiated in monolayerculture.
12
,
26
,
27
While some concerns have been expressed regarding the safety
of these natural polymers,
28
current review indicates that pure algi-
nateissafeforimplantation.
37
Also,humanclinicaltrialsusingultra-
purified alginate-agarose constructs with autologous chondrocytes
(Cartipatch) to repair focal cartilage defects have not shown any
adverse events and have shown good functional improvement up to
two years postoperation.
29
36.2.1
Alginate
Alginateisanioniclinearpolysaccharideconstructedof(1,4)-linked
β
-D-mannuronic acid (M) and
α
-L-guluronic acid (G) monomers
(Fig. 36.3a) arranged in block repeats such as MMMMM, GGGGGG,
or GMGMGM, based on its source from brown seaweed (
Phaeo-
phyceae
)
30
or bacteria.
31
,
32
In general alginate that has more
G-blocks will be stiffer than one that is mixed (for example,
MGMGMG).
33
While seaweed-based alginate is more popular than
bacteria-based alginate (especially in the food industry
33
), due to
its low cost, bacterial alginates, which can be produced in a more
controlled manner, are worth consideration for tissue engineering
purposes. Alginate is cross-linked to form a gel in the presence of
divalent cations. The gelling structure of calcium-alginate is simi-
lar to an eggbox structure (Fig. 36.3b). Mainly, it involves entrap-
ment of cations within two cavities formed by diguluronate so that
the chains are “locked” to each other and a hydrogel is formed
almost instantaneously.
34
The stiffness of the gel depends on the
chain length, monomer sequence, molecular weight distribution,
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