Biomedical Engineering Reference
In-Depth Information
deposition and upregulated chondrogenic gene expression in RGD-modified PEG
diacrylate hydrogels. An in vivo study using predifferentiated human ESC-derived
MSCs demonstrated the potential application of this cell type for osteochondral
tissue repair, indicated by a smooth articular cartilage surface and architecture of
repaired cartilage similar to that of normal cartilage [
133
].
Although RGD-incorporating hydrogel systems have shown the capacity to
induce in vitro chondrogenesis and possible approaches to stimulate in vivo
articular cartilage repair, there have also been some controversial results with use
of RGD-modified materials [
134
,
135
]. For example, bovine MSCs encapsulated
in unmodified alginate gels have been shown to enhance chondrogenic gene
expression and matrix accumulation, whereas this observation was not found in
RGD-modified alginate gels [
134
,
135
]. However, it was found that the inhibition
of sulfated GAG synthesis was stimulated by increasing RGD density [
134
,
135
].
Another study also reported apoptosis of chondrocytes and synovial cells could be
induced by RGD peptides [
135
].
7.2 Growth Factor Incorporation
Chondrogenic differentiation of progenitor cells into mature chondrocytes, cartilage-
specific ECM deposition, and articular cartilage regeneration require a dynamic
interaction of various growth factors as soluble signaling molecules to initiate, stim-
ulate, and maintain differentiated cell function. A number of studies have investigated
the functions of specific growth factors with a given progenitor cell population in
a synthetic environment as well as the influence of combinations of growth factors in a
dynamic fashion. Members of the TGF-b superfamily, such as certain TGF-bsand
BMPs, have been found to aid in the upregulation of type II collagen, SOX9,
and aggrecan expression. Specific molecules that have shown promising results
for chondrogenesis include TGF-b
1
, TGF-b
2
,andTGF-b
3
[
49
,
52
,
136
-
141
], IGF-1
[
142
-
146
], BMP-2, BMP-4, BMP-6, and BMP-9 [
55
,
147
-
151
], and FGF [
152
-
158
].
Combinational and dynamic effects of these growth factors on chondrogenic differ-
entiation and articular cartilage repair have also been investigated [
144
,
158
-
160
].
Effective delivery of growth factors is of importance to induce the chondrogenesis of
progenitor cells and enhance articular cartilage regeneration. In addition to selection
of the growth factor and the combination of a series of growth factors, other
parameters such as the dose and release kinetics are also of importance to augment
cartilage repair. To this end, sustained, controlled growth factor delivery to defect
sites by using various delivery vehicles has also been investigated.
7.2.1 Gelatin Microparticles
Among a number of available methods to incorporate a growth factor into a
scaffold or matrix material, gelatin microparticles (GMPs) have been intensively
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