Biomedical Engineering Reference
In-Depth Information
and timing of exposure, and ligand presentation modulate the level of morphogen
activity and cellular signaling to regulate cell fate and functions [
126
,
134
].
Synthetic hydrogel systems enable delivery of morphogens in a spatiotempo-
rally-controlled manner that affects signalling. Direct encapsulation is the conven-
tional method of delivery in hydrogels, but limitations of this approach include
poor control of release profiles. Often, there will a burst release profile, which
may result in adverse cellular responses and tissue reactions [
135
]. One attractive
approach to overcome this limitation is to incorporate into the hydrogels micro or
nanoparticle delivery vehicles that may allow single or multiple growth factors to
be released in a controlled and sustained fashion [
101
]. In order to further improve
the growth factor stability and specificity, there are also efforts to identify the
functional peptide domain sequences of growth factors, including those that bind
to growth factor receptors and proteoglycans including heparin sulfate, as an alter-
native to the use of entire growth factor [
136
,
137
].
In addition to the control of single or multiple growth factor release, spatial dis-
tribution of the growth factors within the 3-D hydrogel microenvironment could
influence specific cellular processes. Wylie and colleagues used barnase-bastar and
streptavidin-biotin binding pairs to immobilize sonic hedgehog (SHH) and ciliary
neurotrophic factor (CNTF), respectively into modified agarose gel, thereby creat-
ing immobilized gradients of growth factors in distinct regions within the hydrogel
microenvironment for guided cell migration and differentiation [
138
].
4.3 Support Cells
Support cells play important roles in regulating the self-renewal, mobilization and
differentiation of stem cells. Support cells can interact with stem cells by direct
contact through receptors and gap junctions, and by paracrine secretion of growth
factors to influence cell fate and functions. In adult tissues, such as the adult brain,
it has been shown that the adult hippocampal NSC proliferation occurs in a vascu-
lar niche where there is endothelial component of the vasculature, while NSC dif-
ferentiation is promoted by contact with astrocytes [
139
]. The concept of support
cells is perhaps best represented in vitro by the use of feeder cells [
140
] and feeder
cell-derived matrices [
141
,
142
] to support the self-renewal and pluripotency of
hESCs.
In application of stem cells for tissue regeneration, support cells are often com-
mitted cell types that can be co-cultured with the stem cells to direct specific dif-
ferentiation [
143
,
144
]. In this instance, hydrogels serve as a platform to control
the interactions between the stem and support cells [
145
] and as a delivery system
to enable delivery of multiple cell types for regeneration of complex tissues [
146
].
It has been shown in several studies that co-delivery of stem cells and support cells
have synergistic effects in tissue regeneration [
146
,
147
].
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