Hydroxyapatite-Biodegradable Polymer Nanocomposite Microspheres Toward Injectable Cell Scaffold - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 234

necrosis (P, 0.05 vs. BMNC alone or co-injection of BMNC with uncoated
microspheres). The co-injection of BMNC with composite microspheres
revealed much higher induction of angiogenesis in ischemic tissues and
collateral blood fl ow confi rmed by three-dimensional computed tomog-
raphy angiography than those of BMNC alone or co-injection of BMNC
with uncoated microspheres. The enhanced therapeutic angiogenesis
and arteriogenesis by co-injection of BMNC with nanocomposite micro-
spheres showed good correlations with increased intramuscular levels
of vascular endothelial growth factor and fi broblast growth factor-2. The
co-injection of BMNC with composite microspheres also prevented apop-
totic cell death of transplanted cells, resulting in prolonged cell retention.

9.6 Degradation Behavior of HAp-Biodegradable

Polymer Nanocomposite Microspheres

The HAp nanocrystal-coated PLLA microspheres have been proven to be
very effective as an injectable scaffold for cell-based therapeutic angiogen-
esis. For this purpose, it is ideal that the microspheres retain their spheri-
cal biodegradable polymer core/HAp nanocrystals shell morphology
until they fi nish their roles as a scaffold and then are degraded into small
fragments/molecules, which can be discharged out of body. Bearing this
situation in mind, we felt that it is crucial to evaluate degradability of the
HAp nanocrystal-coated biodegradable microspheres. There have been
lots of reports on fabrication of biodegradable polymer microspheres, but
there is little work on the characterization of their degradation behaviors.
This omission is quite surprising, since the biodegradable polymer micro-
spheres are widely used in the medical fi eld.
Based on this situation, in vitro degradation behavior of the HAp nano-
crystal-coated PLCL microspheres has been studied in buffer solution
(PBS) at 37 C in terms of weight, molecular weight, thermal property, and

morphological change during an incubation period of up to 48 weeks [61].
It was found that molecular weight decreased rapidly after immersing the
microspheres in the PBS at 37

°

C and, on the other hand, the weight of the
microspheres started to decrease after 16 weeks, which was the similar deg-
radation profi le with the pristine PLCL bulk sample. This result supports
the bulk degradation for the HAp nanocrystal-coated PLCL microspheres.
During the degradation, the enthalpy of melting increased progressively,
which should be due to the increase of crystallinity because of chain rear-
rangement of amorphous region induced by water uptake and the prefer-
ential degradation of amorphous regions. The HAp nanocrystals detached
from the microsphere surface during the degradation, which was confi rmed
by SEM study. The microspheres were fragile and easy to be broken by
external pressure when the molecular weight became at and below 35,000

°