Biomedical Engineering Reference
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cell-based therapeutic angiogenesis with bone marrow mononuclear cells
(BMNCs) [66]. For the angiogenesis experiments, highly-crystallized
HAp nanoparticle-coated microspheres were used rather than poorly-
crystallized HAp nanoparticles, because the surface stability of the micro-
sphere over 2 weeks (low solubility of HAp component) is important for
BMNCs scaffold (Figure 9.12). Various angiogenic growth factors derived
from implanted cells are key mediators of therapeutic angiogenesis.
However, about 70-90% of the transplanted cells were estimated to disap-
pear from the injection site within 1 week after transplantation [67-69].
Therefore, the effi cacy of the cell-based therapeutic angiogenesis could be
dependent on the retention, survival, and engraftment of implanted cells in
ischemic tissue after implantation. When BMNCs derived from enhanced
green fl uorescent protein (GFP) transgenic mice were coinjected with the
composite microspheres into ischemic muscle, the GFP level in the muscle
was approximately 5-fold higher than that in the case of injection of BMNC
alone 1 week after injection; whereas GFP levels were not signifi cantly dif-
ferent between the injection of BMNCs alone and or co-injection of BMNC
with uncoated PLLA microspheres. These results indicate that the HAp
nanocrystals coated on the microspheres promoted BMNC adhesion and
retention in vitro . Kaplan-Meier analysis demonstrated that co-injection
of BMNC with composite microspheres markedly prevented hind limb
( a )
( c )
PLLA
100 nm
HAp
100 μm
1 μm
( b )
( d )
100 nm
100 nm
1 μm
1 μm
Figure 9.12 SEM photographs of (a-c) HAp nanocrystal-coated and (d) bare
PLLA microspheres observed at different magnifi cations: (a) 100×; (b-d)
5000×(inset) 50,000×. Photograph (c) shows a fractured section of a HAp
nanocrystal-coated PLLA microsphere. Reprinted with permission from [13].
Copyright © 2010 Elsevier.
 
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