Sustained release and osteogenic potential of heparansulfate-doped fibrin glue scaffolds within a rat cranial model
2007
This paper explores the potential therapeutic
role of the naturally occurring sugar heparan sulfate (HS)
for the augmentation of bone repair. Scaffolds comprising
fibrin glue loaded with 5 lg of embryonically derived HS
were assessed, firstly as a release-reservoir, and secondly as
a scaffold to stimulate bone regeneration in a critical size
rat cranial defect. We show HS-loaded scaffolds have a
uniform distribution of HS, which was readily released
with a typical burst phase, quickly followed by a prolonged
delivery lasting several days. Importantly, the released HS
contributed to improved wound healing over a 3-month
period as determined by microcomputed tomography
(lCT) scanning, histology, histomorphometry, and PCR for
osteogenic markers. In all cases, only minimal healing was
observed after 1 and 3 months in the absence of HS. In
contrast, marked healing was observed by 3 months following
HS treatment, with nearly full closure of the defect
site. PCR analysis showed significant increases in the gene
expression of the osteogenic markers Runx2, alkaline
phosphatase, and osteopontin in the heparin sulfate group
compared with controls. These results further emphasize
the important role HS plays in augmenting wound healing,
and its successful delivery in a hydrogel provides a novel
alternative to autologous bone graft and growth factorbased
therapies.
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