Macroporous Hydrogels Upregulate Osteogenic Signal
Biomacromolecules, Vol. 11, No. 5, 2010 1167
and proliferated on the surfaces of the fibronectin-modified
macroporous EH-PEG hydrogels (Figure 5). Furthermore, and
as expected, hMSCs cultured on surfaces with higher concentra-
tions of fibronectin demonstrated enhanced cell spreading as
compared EH-PEG hydrogels with no fibronectin. When
compared with monolayer controls, hMSCs cultured in EH-PEG
hydrogels exhibit increased osteogenic signaling, as shown by
BMP-2 expression and BMP receptor expression, with no
dependence on fibronectin concentration (Figure 6). However,
when compared with the BMP-2 expression from hMSCs
cultured without the addition of fibronectin (Figures 2 and 3),
we concluded that upregulated BMP-2 expression is predomi-
nately due to macroporous architecture, rather than an increase
in cell adhesion from the incorporation of fibronectin in EH-
PEG hydrogels. Therefore, culturing hMSCs within a macroporous
EH-PEG seems to have significantly contributed to the early
osteogenic signal expression and, as a result, osteoblastic
differentiation.
in promoting osteogenic signal expression. We suggest that the
results of this work may provide an important means to direct
stem cell differentiation beyond those previously described in
the literature. Finally, the results of this study should have a
significant impact on the development of biomaterials for stem
cell therapies.
Acknowledgment. This work was supported by the National
Science Foundation (CAREER Award to J.P.F., no. 0448684)
and the State of Maryland, Maryland Stem Cell Research Fund.
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Conclusions
The objective of this work was to investigate the effects of
macroporous hydrogel architecture upon hMSC osteogenic
signal expression and differentiation. Results showed that
culturing hMSCs within a macroporous hydrogel architecture
significantly upregulates BMP-2 expression and that this up-
regulation promotes quick differentiation. We speculate that this
phenomenon may be primarily due to the macroporous archi-
tecture’s ability to facilitate autocrine and paracrine signaling
by localizing endogenously expressed factors within the hy-
drogel’s water-filled pores. Future studies are required to
examine whether the biomaterial itself plays a significant role