Hydroxyapatite-Biodegradable Polymer Nanocomposite Microspheres Toward Injectable Cell Scaffold - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 219

9.1 Introduction

There is a growing interest in synthesis of hydroxyapatite (HAp,
Ca 10 (PO 4 ) 6 (OH) 2 )-synthetic polymer hybrid materials in a form of micro-
sphere, because they have found their applications in the biomedical fi eld
[1-3]. HAp is one of the calcium phosphates and the main mineral of
bones and teeth in vertebrates, and artifi cially synthesized HAp has been
extensively used in a variety of applications, such as biomaterials in the
orthopedic and dental fi elds, amphoteric ion-exchangers, column packing
materials for protein separation, cosmetics, dentifrices, and as catalysts
by exploiting their biocompatibility and adsorbability with many com-
pounds [4-6]. HAp exhibits excellent adhesion not only to cells but also
to hard and soft tissues [7]. Hybridization of HAp and synthetic polymers
is important in order to give the materials high cell adhesion property
and desired mechanical property and fl exibility, and various approaches
have been designed to synthesize the HAp-polymer hybrid microspheres
[8-11]. Among the various HAp-synthetic polymer hybrid microspheres,
biodegradable polyester-based microspheres are of great importance due
to their superiority in biodegradability. Poly( L -lactide) (PLLA), poly( e -
caprolactone) (PCL), poly( L -lactide- co - -caprolactone) (PLCL) and poly( L -

lactide- co -glycolide) (PLGA) are biodegradable polyesters, which have
already been used as sutures, orthopedic fi xation devices, barrier mem-
branes, and drug delivery devices in the medical fi eld [12]. These polyes-
ters are unable to interact specifi cally with cells due to their relatively high
hydrophobicity and lack of functional groups for the attachment of bioac-
tive molecules. In order to improve cell adhesion properties of biodegrad-
able polyesters, the hybridization with HAp has been studied. Kang and
coworkers [3] fabricated HAp-coated PLGA microspheres by incubating
PLGA seed microspheres in a simulated body fl uid and claimed their use
as an injectable scaffold for bone regeneration through minimally invasive
surgical procedures in orthopedic applications. HAp-coated PLLA micro-
spheres were also prepared by coating PLLA microspheres with HAp
nanocrystals via interaction between carboxyl groups on PLLA surfaces
and calcium ions on HAp [13]. Lv and coworkers [14] synthesized HAp-
PLGA hybrid microspheres, which are suitable for microsphere sintered
cell scaffolds, by emulsion solvent evaporation method. Qiu and cowork-
ers [15] prepared HAp nanoparticle/PLLA hybrid microspheres by a
solid-in-oil-in-water emulsion solvent evaporation method.
In the abovementioned systems, the biodegradable microspheres
were fabricated by an oil-in-water emulsion solvent evaporation method
[3, 13-15]: the molecular-level emulsifi ers (low-molecular-weight surfac-
tants or polymeric colloidal stabilizers), which are suspected of causing
allergy-like reactions and carcinogenicity [16, 17], were usually required
to stabilize oil droplets and the microspheres in aqueous media. However,

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