Gelation Characteristics
and Osteogenic Differentiation
of Stromal Cells in Inert Hydrolytically Degradable Micellar Polyethylene
Glycol Hydrogels
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Abstract
The use of poly(ethylene glycol) (PEG) hydrogels in tissue
engineering
is limited by their persistence in the site of regeneration. In an
attempt to produce inert hydrolytically degradable PEG-based hydrogels,
star (SPELA) poly(ethylene glycol-<i>co</i>-lactide) acrylate
macromonomers with short lactide segments (<15 lactides per macromonomer)
were synthesized. The SPELA hydrogel was characterized with respect
to gelation time, modulus, water content, sol fraction, degradation,
and osteogenic differentiation of encapsulated marrow stromal cells
(MSCs). The properties of SPELA hydrogel were compared with those
of the linear poly(ethylene glycol-<i>co</i>-lactide) acrylate
(LPELA). The SPELA hydrogel had higher modulus, lower water content,
and lower sol fraction than the LPELA. The shear modulus of SPELA
hydrogel was 2.2 times higher than LPELA, whereas the sol fraction
of SPELA hydrogel was 5 times lower than LPELA. The degradation of
SPELA hydrogel depended strongly on the number of lactide monomers
per macromonomer (nL) and showed a biphasic behavior. For example,
as nL increased from 0 to 3.4, 6.4, 11.6, and 14.8, mass loss increased
from 7 to 37, 80, 100% and then deceased to 87%, respectively, after
6 weeks of incubation. The addition of 3.4 lactides per macromonomer
(<10 wt % dry macromonomer or <2 wt % swollen hydrogel) increased
mass loss to 50% after 6 weeks. Molecular dynamic simulations demonstrated
that the biphasic degradation behavior was related to aggregation
and micelle formation of lactide monomers in the macromonomer in aqueous
solution. MSCs encapsulated in SPELA hydrogel expressed osteogenic
markers Dlx5, Runx2, osteopontin, and osteocalcin and formed a mineralized
matrix. The expression of osteogenic markers and extent of mineralization
was significantly higher when MSCs were encapsulated in SPELA hydrogel
with the addition of bone morphogenetic protein-2 (BMP2). Results
demonstrate that hydrolytically degradable PEG-based hydrogels are
potentially useful as a delivery matrix for stem cells in regenerative
medicine