Harnessing Cell–Biomaterial Interactions for Osteochondral Tissue Regeneration - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 77

ADSCs in direct contact with porous native articular cartilage ECM showed
increased expression levels of type II collagen and aggrecan, with decreased levels
of type X collagen in the absence of chondrogenic growth factors in the culture
medium. These results indicate the importance of cell-matrix interactions for
chondrogenic differentiation of ADSCs [ 62 ]. Additionally, the interaction of
ADSCs with biomaterials can further influence chondrogenesis. For instance,
biomaterials such as alginate and agarose, which naturally lack attachment
sequences, allow ADSCs to maintain a rounded morphology. However, in fibrin or
gelatin hydrogels, which contain cell binding sites, ADSCs tend to spread and
become more fibrochondrogenic [ 63 ]. ADSCs entrapped within elastin-like
polypeptides with repeating sequences of Val-Pro-Gly-Xaa-Gly, where Xaa is any
amino acid except proline, were able to synthesize high levels of type II collagen,
with low type I collagen formation in the absence of chondrogenic medium for at
least 2 weeks [ 64 ]. Human ADSCs cultured on silanized hydroxypropylmethyl-
cellulose hydrogels demonstrated higher type II collagen, COMP, and SOX9
expression in 3D culture versus 2D culture without chondrogenic medium.
However, to form cartilage matrix in vivo, culture of ADSCs in chondrogenic
medium was necessary [ 65 ]. The preculture of ADSCs with chondrogenic medium
has been found in other studies to be effective in the growth of cartilage ECM in
vivo. When ADSCs are grown in a monolayer with chondrogenic medium and
then subcutaneously implanted with alginate, an increase in type II collagen,
COMP, aggrecan, and SOX9 expression was exhibited after 20 weeks, but there
were low levels of type I and type X collagen [ 66 ]. ADSCs in micromass culture
with TGF-b 1 have been grown in an atelocollagen honeycomb-shaped scaffold and
placed into an osteochondral rabbit defect [ 67 ]. Although cartilage-like tissue
formed in the scaffold with and without ADSCs, larger amounts of cartilage tissue
and the histological scoring of the tissue indicated that the presence of ADSCs
results in improved cartilage repair.
5.1.3 Embryonic Stem Cells
Human embryonic stem cells (ESCs) are pluripotent cells that are derived from the
inner mass of the embryonic blastocyst. ESCs are self-maintaining and are able to
proliferate indefinitely [ 68 ]. Even though the use of these cells is subject to ethical
debate, there have been initial promising signs of their ability to differentiate into
chondrocytes. Successful chondrogenesis of ESCs was initially thought to require
the formation of embryoid bodies (EBs) [ 69 ]. Enzymatically dissociated EB cells
cultured in 2% agarose with chondrogenic medium without any exogenous growth
factors showed higher collagen and sulfated GAG content than native EBs [ 70 ].
Exposing ESCs to BMP-2, BMP-4, and BMP-7 has been found to aid in the
expression of cartilage matrix, but TGF-b 1 can hinder chondrogenic differentiation
of these cells [ 71 - 74 ].