Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 91

hydrogels [ 118 ]. This study demonstrated that the unique mechanical properties
and ECM composition of each formulation might direct a zonal-phenotype-
specific chondrogenic differentiation. The result indicated that the PEG/CS/MMP-
sensitive peptide group corresponded to the superficial zone, the PEG/CS group
corresponded to the middle zone, the PEG/HA group corresponded to the deep
zone, and the CS group corresponded to the calcified zone.
8.2 Bilayered Hydrogels
In addition to zonal engineering of articular cartilage, implantable bilayered
hydrogel systems have also been investigated for osteochondral tissue regeneration
with two distinct sublayers. Osteochondral tissue contains an articular cartilage
surface at the top and subchondral bone underneath the cartilage tissue that pro-
vides mechanical support [ 206 - 208 ]. Therefore, biphasic layers with distinct
biomechanical properties could simultaneously mimic the chondrogenic surface as
well as the bony subchondral tissue. For the full-thickness joint defect,
an approach using a bilayered structure of implantable hydrogel or scaffold could
induce osteochondral tissue regeneration.
A composite bilayered hydrogel of OPF matrix and growth factor-incorporating
GMPs has been studied as a functional model for osteochondral tissue regeneration
[ 209 - 211 ]. An early in vivo trial with this composite hydrogel demonstrated the
support of healthy tissue growth in New Zealand White rabbit osteochondral
defects by showing hyaline cartilage improvement in the chondral region and bone
filling in the subchondral region at 14 weeks [ 211 ]. In this study, hydrogel com-
posites of 3-mm diameter and 3-mm thickness were implanted in the full-thickness
defect of a rabbit knee joint. The TGF-b 1 -loaded chondral layer exhibited a sig-
nificant improvement in morphology of neoformed surface tissues among various
histological scoring criteria compared with gels encapsulating blank GMPs
without the growth factor. Additionally, the in vitro influence of the differentiation
stage of an encapsulated cell population in this hydrogel system was also inves-
tigated [ 210 ]. A combination of MSCs with TGF-b 1 -loaded GMPs in the chondral
(top) layer and osteogenically induced (6 days of culture in medium with osteo-
genic supplements) MSCs with blank GMPs in the subchondral (bottom) layer
showed significantly higher mRNA expression levels of collagen type II and
aggrecan compared with both nonosteogenic cells and TGF-b 1 -free groups. This
study demonstrated that osteogenic cells in the subchondral region might produce
chondrogenic-signaling molecules to induce chondrogenic differentiation of MSCs
in the chondral layer. This observation was only seen in the presence of TGF-b 1 ,
which indicated the importance of the additional effect of growth factor on MSC
differentiation in a hydrogel system. Similarly, precultured MSCs in medium with
osteogenic supplements in the subchondral layer with the aid of TGF-b 3 induced a
significantly higher level of in vitro chondrogenesis of MSCs in a chondral layer
after 28 days of culture compared with groups without TGF-b 3 [ 209 ].