Biomedical Engineering Reference
In-Depth Information
4.3.2.1.1 Nano- or Microparticles
Nano- or microparticles are among the most
common types of delivery vehicle for bioactive
molecules. A variety of microparticles
fabricated with polymers such as poly(
-
caprolactone) (PCL), poly(lactic acid) (PLA),
poly(lactic-co-glycolic acid) (PLGA), or blends
of PLGA with poly(ethylene glycol) (PEG) have
been investigated as delivery matrices for
orthopedic applications. These microparticles
can be formed by several methods, such as a
single/double emulsion technique or a solvent
evaporation-extraction process. Because the
mechanism by which bioactive molecules are
released in these systems is mainly diffusion,
the release rate and total amount released can
be adjusted by altering fabrication parameters
such as loading concentration, polymer molec-
ular weight, copolymer ratio, and particle
structure [
ε
].
Alternatively, release from nano- or mic-
roparticles made of naturally derived materials
can be controlled through directed degrada-
tion rather than a diffusion mechanism, as in
the polymeric systems described above. When
transforming growth factor
24
,
47
,
89
,
104
) was
incorporated into gelatin microspheres, the
release profi les depended on the presence of a
gelatinase enzyme in the medium. In this case,
it is likely that the polyionic complexation
between the growth factor and the gelatin
retards its release until the gelatin microparti-
cle is degraded by the enzyme. Because enzymes
such as matrix metalloproteinases (MMPs) are
up-regulated in injured cartilage, this system
may provide a unique mechanism to encourage
drug release in areas undergoing tissue remod-
eling [
β
1
(TGF-
β
1
Figure 4.2.
Light microscopy of oligo(poly(ethylene glycol)
fumarate) (OPF) hydrogel composites containing chondrocytes
at day 21. Arrows indicate encapsulated chondrocytes, and
arrow heads indicate encapsulated microparticles. OPF hydro-
gel composites containing only chondrocytes are depicted in
(A), while (B) shows OPF hydrogel composites containing
chondrocytes and TGF-
β
1-loaded microparticles. Reproduced
with permission from Park et al. [77]. Copyright 2005, with
permission from Elsevier.
]. An additional advantage of gelatin
microspheres is that when they are encapsu-
lated in hydrogels, they can serve as porogens,
thus providing additional space for tissue for-
mation at the defect site (Fig.
41
tage that they can be designed to function as
biomimetic support materials, as well as drug-
delivery matrices [
]. Moreover, depending on
their composition, hydrogels may be injectable,
allowing for their use in minimally invasive
procedures. In one study, PEG-based mac-
romers were photopolymerized to encapsulate
DNA. By changing the monomer chemistry in
this system, the DNA release profi le was
tailored to provide release over
85
4
.
2
) [
41
,
77
].
4.3.2.1.2 Hydrogels
Hydrogels are three-dimensional polymers
physically or chemically cross-linked and
swollen by water. This enables them to entrap
various drugs and later release them in a con-
trolled manner. The release kinetics of drugs
from hydrogels can be modulated by external
stimuli such as changes in pH [
6
to
100
days
[
]. Another PEG-based oligomer, oligo(poly
(ethylene glycol) fumarate), has also been
developed as an injectable hydrogel carrier for
growth factors useful for both bone and carti-
lage tissue engineering [
82
52
], temperature
[
]. For the treatment of
orthopedic defects, hydrogels have the advan-
50
], or protein levels [
80
40
,
41
,
54
].
