Biomedical Engineering Reference
In-Depth Information
placements. Given the fact that the source of cells for repair is limited in such
cases, it is desirable to exploit other cell lines. It is well documented in the
literature that expansion of chondrocytes results in a loss of their phenotype
as discussed earlier. Using biomaterial scaffolds and growth factors to re-
differentiate the chondrocytes that have de-differentiated during monolayer
expansions has had little success so far. For instance, Homicz et al. showed
that only primary chondrocytes (immediately harvested prior to expansion)
are suitable as seed cells for cartilage tissue engineering [309]. Chondro-
cytes that are used from subsequent passages produced decreased amounts
of aggrecans and type II collagen as compared to those produced by primary
cells. This therefore limits the mechanical as well as structural properties of
the formed neocartilage [309]. Since chondrocytes lose their phenotype dur-
ing expansions, it becomes necessary to start with a large biopsy to achieve
enough cells for tissue engineering a cartilage sufficient in size for implan-
tation. This leads to the primary constraint in using differentiated cells for
cartilage tissue engineering, the lack in achieving adequate cell numbers. To
circumvent the above constraint, scientists have begun to use stem cells (adult
and embryonic) in tissue engineering for replacing dysfunctional tissues.
This also avoids problems related to harvesting tissue as well as morbidity
associated with the biopsy.
Nonhematopoietic stem cells (mesenchymal stem cells, MSCs) which are
present in the bone marrow are multipotent, or in other words, they are
capable of differentiating into various lineages such as cartilage [22, 310],
bone [31, 311], connective tissues [312], etc. The differentiation of MSCs into
a specific lineage requires a synergetic interaction between the cells and var-
ious insoluble and soluble growth factors during their culture [22, 313, 314].
This means that the tissue engineering scaffold needs to mimic the ECM
components both structurally and functionally in order to provide the de-
sired signals to direct cellular processes when using stem cells. Most of the
first generation hydrogel scaffolds provides structural supports for the en-
capsulated cells but lack the required functional (biological) support. To
increase the biofunctionality of the hydrogel scaffold one may covalently graft
bioactive factors such as adhesion peptides or growth factors to the hydro-
gel [147, 315].
Micromass pellet cultures have shown the ability of MSCs to undergo
chondrogenesis by providing enhanced cell-cell interactions [310]. However,
to create organized tissues for treating large defects, support from three-
dimensional scaffolds is required. Such three dimensional scaffolds accom-
modate a sufficient amount of cells, define the engineered tissue architecture,
and may also be decorated with suitable biochemical cues to enhance the
cell-matrix interactions. Hydrogels composed of various synthetic as well as
natural polymers such as PEGDA, silk, collagen, etc., have been explored for
the differentiation of MSCs into chondrocytes and osteoblasts [22, 230, 231]. In
our laboratory, we investigated the ability of MSCs to undergo chondrogenesis
