Hydroxyapatite-Biodegradable Polymer Nanocomposite Microspheres Toward Injectable Cell Scaffold - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 227

defl ate to maintain the interfacial area. From the above described results,
it is clear that morphology control of the formed microspheres is possible
by controlling the degree of interaction between the polymer dissolved in
the oil phase and the HAp nanoparticles [51]. In addition to the molecular
weight of the polymer dissolved in the oil phase, the type of polymer, the
chain end structure of the polymer, the evaporation rate of the oil, the
homogenization rate during oil evaporation, and the type of oil are factors
that can affect the morphology of the nanocomposite microspheres.

9.3.2 Fabrication of HAp-Biodegradable Polymer

Nanocomposite Microspheres

The Pickering emulsion method enables the fabrication of nanocompos-
ite microspheres without the use of a molecular-level emulsifi er. Thus,
we have been studying the synthesis of biodegradable polymer-HAp
nanocomposite microspheres by the Pickering emulsion method, target-
ing the biomedical material fi eld, where the presence of molecular-level
emulsifi ers is unfavorable because of their toxicity and allergic proper-
ties [52-54, 57-61]. As the biodegradable polymer, PLLA, PCL, PLCL, and
PLGA, which have been clinically proven to be safe and are in practical
use, were selected. These biodegradable polymers have ester groups in
the main chain of the molecule and a carboxyl group as the chain end
group. Therefore, they can be expected to interact with HAp nanoparticles
(or nanocrystals), resulting in the formation of a stable emulsion and the
fabrication of nanocomposite microspheres. In fact, FT-IR studies detected
the absorption at 1595 cm -1 due to the -COO - Ca 2+ ionic bond in a mixture of
PLLA and HAp nanoparticles, which is formed by the interaction between
carboxylate groups (originated from carboxyl end groups) and calcium ions
on the HAp nanoparticle surface in addition to the absorption at 1760 cm −1 ,
which was assigned to the carbonyl and carboxyl groups found in PLLA
homopolymers (Figure 9.6). For the other biodegradable polymers, simi-
lar HAp-polymer interaction was confi rmed by FT-IR measurements.
Homogenization of CH 2 Cl 2 solution of the above described biodegradable
polymers with an aqueous dispersion of HAp nanoparticles led to the for-
mation of a stable emulsion in all the systems. In addition, nanocompos-
ite microspheres with biodegradable polymer core/HAp nanoparticles
shell morphology were obtained by removing CH 2 Cl 2 . Optical microscope
studies confi rmed that the emulsion droplets do not coalesce during the
CH 2 Cl 2 evaporation process (Figure 9.7). It was also clarifi ed by gas chro-
matography (GC) measurements that the CH 2 Cl 2 concentration decreased
from 68,000 ppm to 240 ppm after 6 h from the start of evaporation and
reached the GC measurement limit of less than 10 ppm after 13 h. The
International Conference on Harmonization of Technical Requirements
for Registration of Pharmaceuticals for Human Use (ICH) has classifi ed