Biomedical Engineering Reference
In-Depth Information
For the successful tissue regeneration, we need to better understand cell-matrix
interactions. Stem cells can be differentiated into specific lineages through the
interaction between cell and biological cues or between cell and physical cues
[
127
]. Physicochemical properties of photodegradable PEG based hydrogels could
be dynamically controlled by light [
9
]. Crosslinking density of hydrogel decreased
via photodegradation and facilitated spreading or migration of embedded cells. In
addition, MSCs showed enhanced chondrogenesis when cell adhesive sequence of
Arg-Gly-Asp-Ser (RGDS) was photocleaved from hydrogels. Neurogenesis, myo-
genesis, and osteogenesis of stem cells on 2D gel surface were controlled by vary-
ing stiffness of the hydrogel surface from 0.1-1 kPa, 8-17 kPa, and 25-40 kPa,
respectively [
128
]. Three-dimensional culture of mesenchymal stem cells in
RGD-modified alginate hydrogels also showed stem cell differentiation is corre-
lated to the hydrogel stiffness [
129
]. Briefly, adipogenesis or osteogenesis was pre-
dominantly occurred in 2.5-5 kPa or 11-30 kPa microenvironments, respectively.
However, cell morphology remained spherical regardless of modulus. MSCs cul-
tured in matrix metalloproteinase (MMP) degradable hydrogels showed high
degrees of cell spreading followed by osteogenic differentiation, while remained
spherical and underwent adipogenesis in non-degradable hydrogels [
14
]. MSCs
can be induced various differentiation through the interactions between cells and
small functional groups in hydrogels [
130
]. Specifically, phosphate or alkyl groups
in PEG hydrogel induced osteogenesis or adipogenesis, respectively. Human adi-
pose derived stem cells (hADSCs) encapsulated in PEG hydrogels with multifunc-
tionalized
ʱ
-CD nanobeads regulated stem cell fate [
131
]. Ultimately, the alcohol,
hydrophobic methyl group, and phosphate-substituted
ʱ
-CD nanobeads stimulated
chondrogenic, adipogenic, and osteogenic differentiation, respectively.
7 Conclusions and Prospectives
In situ forming chemically and/or physically crosslinked hydrogels under mild
conditions have been developed for various biomedical applications. Injectable
hydrogel systems are minimally invasive and patient friendly. We can decrease
injection frequency for better patient compliance by developing novel sustained
drug delivery systems. Cells or bioactive molecules are easy to mix with poly-
mer solutions and these mixtures are in situ and easy to form the 3D microen-
vironments into any desired defect shapes. For successful designing of an in situ
gelling system for a specific biomedical application, several points should be
carefully understood. (1) Different crosslinking type gives different degradation
products and release-profiles of incorporated drugs. (2) Porosity and pore size
of hydrogels can affect to cell viability, proliferation, and/or drug release profile.
(3) Initiators, catalysts, or residual monomers can lead cytotoxicity. During radi-
cal polymerization, produced radicals not only can react with the vinyl group in
monomer but also can damage cellular macromolecules. (4) Reactive functional
groups of polymers can give side reactions with incorporated bioactive molecules
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