ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 320

A C

B B

Fig. 2. In vitro chondrogenic differentiation of chondrogenic-committed cells derived from hESCs
in PEG-based hydrogels. (Reprinted with permission from Hwang NS, Varghese S, Elisseeff J
(2008) PLoS ONE 3(6): e2498).

In a study by Salinas et al. [244, 271] the RGD peptides were incorporated into
PEG hydrogels either as pendant attachments or dually attached as crosslinker or
embedded in the backbone of the polymer. In addition, a RGD peptide with an
eight-glycine spacer (C(G) 8 RGDSG) was also used to modify hydrogels. The
viability of hMSCs in hydrogels after 2 weeks of culturing in MSC medium was
found to be 79%, 84% and 61% for pendantly attached without a spacer,
pendantly attached with the spacer and dully attached, respectively. Therefore,
the spacer and pendant attachment of RGD peptide sequences for cell adhesion
are favorable. Furthermore, integrin receptors for ŋ v Ȳ 3 correlated to the trends in
hMSC survival [244].
Now, it becomes clear that the integrin-mediated adhesion is only necessary
at the onset of differentiation down the chondrogenic path for MSCs [221].
Down-regulation of fibronectin is correlated with maturation of chondrocytes
[221, 272]. Therefore, the presence of RGD peptides in hydrogels is favorable
for early stages of chondrogenesis, while limiting complete differentiation of
MSCs. In one study, the chondrogenesis of MSCs in RGD-modified alginate was