ENGINEERING PEPTIDES IN HYDROGELS FOR CARTILAGE TISSUE REGENERATION - Biologically-Responsive Hybrid Biomaterials - page 323

achieved compared to those by MSCs encapsulated PEG hydrogels. In addition,
by incorporation of CMP peptides, the hypertrophic differentiation was inhibited,
which was evidenced by down-regulation of both type X collagen and cbfa -1, an
essential transcriptional factor for osteoblast differentiation. Improved retention
of MSC-secreted collagen was believed to contribute to enhanced chondrogenic
differentiation of MSCs. Salinas and Anseth [279] derived a peptide (CKLERG)
containing KLER, one of the two major decorin binding sites for type II collagen
and pendantly conjugated the peptide into PEG hydrogels via a photoinitiated
thiol-acrylate polymerization with PEGDA. A RGD peptide CRGDSG was also
incorporated into the gels for promoting cell survival. hMSCs were encapsulated
in the hydrogels with 1 mM of CRGDSG and 5 mM of CKLERG. During a 6-
week period of culture in chondrogenic medium, the production of both GAG
and type II collagen was much higher compared to all controls including
hydrogels with RGD peptides only. The expression of chondrogenic gene
markers such as aggrecan and type II collagen was also increased in hydrogels
conjugated with decorin peptides. These improvements in chondrogenesis were
suggested to the better ECM organization by decorin moieties.
6.3. Remodeling for neo-cartilage tissue formation and integration of
engineered tissue
Hydrogels with degradable property or even more sophisticated cell-responsive
degradation is highly desirable for cartilage tissue engineering [52]. Scaffolds
provide temporal physical support for cells in tissue engineering. However,
following neo-tissue formation, it will be very important for the scaffolds to be
remodeled passively or actively by cells to accommodate cellular residents and
newly deposited ECM. This will result in organizing cellular contents in
engineering tissue constructs and inducing desirable tissue regeneration as well
as integration of neo-tissue. As discussed above, MMPs, especially MMP-13,
play very important roles in the chondrogenesis [220]. Their expression is
coincident with the process of chondrogenic differentiation. Based on these,
MMP-degradable scaffolds have been exploited in cartilage tissue engineering.
Hubbell and colleagues [247, 280] pioneered the application of MMP-sensitive
hydrogels in tissue engineering and showed that degradation of the hydrogels by
cell-secreted MMPs facilitated cell invasion [280]. Park et al. [281] applied the
same MMP-degradable PEG hydrogels for chondrocytes. MMP-sensitive
peptides (GCRDGPQGIWGQDRCG) were designed to bear thiol functionalities
for crosslinking with four- and eight-armed PEG-VS macromers. Primary bovine