Chemistry Reference
In-Depth Information
Scheme 8.9
HA modifications with methacrylic (MA) (
a
) and polycaprolactone-MA (PCL-MA)
and (
b
) moieties proposed by Burdick et al. [
69
,
70
]
long-term hydrolytic resistance, thanks to a reduced recognition of the cross-linked
material by hyaluronidase [
68
]. However, to facilitate chondrocyte growth, an
appropriate temporal degradation of the scaffold should occur, because cells need
more space to receive nutrients and to clear wastes. The introduction of hydrolyti-
cally degradable polyester chains, such as PCL, has been successfully designed to
improve scaffold hydrolysis rate with time [
69
,
70
].
Mixing different weight ratios of not grafted and PCL-grafted HA-MA
derivatives, it was possible to properly control the rate of hydrolysis of chondrocyte
or mesenchymal stem cell-loaded scaffolds. In particular, hydrogel obtained by
cross-linking HA-MA and HA-g-PCL-MA in a ratio 1:1 with a concentration of
2 % w/v had the best rate of hydrolysis, enough to allow a uniform deposition of
collagen II and GAG inside the hydrogel. Chemically cross-linked hydrogels based
on HA-MA alone have instead a rate of hydrolysis too slow, and they do not permit
a uniform deposition of ECM matrix, thus producing a neocartilage with lower
mechanical properties.
A HA-g-PLGA was proposed recently by Park and colleagues as suitable
derivative for the production of scaffolds by solid free-form fabrication technique
(SSFF). The SSFF allows the production of micro-engineered scaffolds with
ordered morphologies. The core of the system is a computerized multihead deposi-
tion system that controls the injection of thin layers of the polymeric solution in a
hot air-conditioned box. Upon evaporation of the solvent, the polymeric solution
solidifies producing the scaffold. The HA-g-PLGA copolymer was produced
starting from a HA with a molecular weight of 20,000 Da through the formation
of the hydrazide-functionalized HA-ADH derivative (see Scheme
8.6
a). This
hydrazide-terminated HA derivative was then employed for the grafting with