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A SUGAR-BASED PHASE-TRANSITIONING DELIVERY SYSTEM FOR BONE
208
TL Cheng et al. SAIB for bone tissue-engineeringEuropean Cells and Materials Vol. 26 2013 (pages 208-221) ISSN 1473-2262
Abstract
Bone tissue engineering approaches commonly involve
the delivery of recombinant human bone morphogenetic
proteins (rhBMPs). However, there are limitations
associated with the currently used carriers, including
the need for surgical implantation and the associated
increase in infection risk. As an alternative to traditional
porous collagen sponge, we have adopted a solution of the
injectable sucrose acetate isobutyrate (SAIB) as a carrier
for rhBMP-2. The ability to deliver rhBMP-2 and other
agents by injection reduces the infection risk and lesion size
whilst in surgery, with the potential to avoid open surgery
altogether in some indications.
The primary methodology used for this in vivo study
was a C57BL6/J mouse ectopic bone formation model.
Specimens were examined by x-ray, microCT, and histology
at 3 weeks. SAIB was delivered non-invasively and produced
up to 3-fold greater bone volume compared to collagen.
To further refine and improve upon the formulation,
SAIB containing rhBMP-2 was admixed with candidate
compounds including ceramic microparticles, anti-
resorptives, and cell signalling inhibitors and further tested
in vivo. The formulation combining SAIB/rhBMP-2, the
bisphosphonate zoledronic acid (ZA), and hydroxyapatite
(HA) microparticles yielded a 10-fold greater bone volume
than SAIB/rhBMP-2 alone. To investigate the mechanism
underlying the synergy between ZA and HA, we used in
vitro binding assays and in vivo fluorescent biodistribution
studies to demonstrate that ceramic particles could bind and
sequester the bisphosphonate. These data show the utility
of SAIB as a non-invasive rhBMP delivery system as well
as descr
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