Hyaluronic Acid Incorporation into Scaffolds for Bone and Cartilage Regeneration - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 39

Cartilage Regeneration

Artz and Synvisc enhanced bone formation compared to the particles
alone, by stimulating osteoclastic resorption of the particles [101].

Composites consisting of bioglass particles suspended in an EDC/ N -
hydroxysuccinimide crosslinked scaffold of HA, collagen, and
phosphatidylserine were evaluated as cell carriers [102, 103]. MSC
exhibited higher cell attachment, proliferation, and migration as well
as higher alkaline phosphatase activity and alkaline phosphatase,
osteocalcin, and osteopontin gene expression on the composites
compared to control scaffolds lacking one or more components [102].
The constructs with MSC led to significant new bone formation in
a rat femur defect model in vivo as well as increased the mechanical
properties of the regenerated femur after 6 weeks of healing [103].
HA hydrogels formed from HA-aldehyde and HA-hydrazide were
also prepared with hydroxyapatite nanoparticles as well as varying
amounts of BMP-2 and tested in a minimally invasive mandibular
bone augmentation procedure in rats [104]. All treatments led to
an increase in bone volume, with a dose response dependent on
BMP-2 concentration [104]. Similar hydrogels prepared from HA-
aldehyde and a hydrazide-modified polyvinyl alcohol, again with
hydroxyapatite and BMP-2, led to significant bone formation in
a minipig critical size cranial defect model [105]. Interestingly, the
macrostructure of the hydrogel also played a role in bone formation,
as different morphologies were observed for ectopic bone formed in
crushed versus solid hydrogels [106].

Additional formulations with HA include an injectable and
thermoresponsive hydrogel, consisting of HA- g -chitosan- g -poly( N -
isopropylacrylamide), which was used to embed biphasic calcium
phosphate microparticles [107]. The composites led to enhanced
proliferation, alkaline phosphatase activity, calcium deposition,
and osteoblastic gene expression by cultured fetal osteoblast cells
[107]. Further, injected hydrogels containing cells could form ectopic
bone tissue in a subcutaneous model [107]. Finally, a hydrogel with
cleavable disulfide linkages, formed from HA and cystamine, was
shown to form the most effective combination for bone regeneration
with the bioactive MegaGen Synthetic Bone substitute in a rabbit