Tissue Engineering: Focus on the Musculoskeletal System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 197

each specific lineage. It is important to note that stem cells were cultured
in a 3D matrix in this study rather than the conventional 2D culture. The
mechanism for differentiation remains unknown; however, the simple trans-
lation from 2D to 3D cell culture is a new trend in biomaterial research and
is continually outputting new and exciting results that will have a significant
impact on the design of future biomaterials.
Hydrogels
Despite the promise of cell-based therapy for tissue engineering, retaining
cell viability upon transplantation remains a major hurdle for cell thera-
pies. Studies have shown that upon transplantation in vivo, cell viability
is extremely low and cells often get rapidly cleared by the spleen and liver
[17, 18]. Possible factors for rapid cell death include immune response and/
or environmental stress on the cells. Encapsulating cells in hydrogels may
help decrease cell death by providing a protective carrier for transplanted
cells. Cell encapsulation was initially demonstrated in the early 1980s for
encapsulating islet cells in an effort to prolong their survival in vivo [19].
Late work has expanded to explore engineering 3D hydrogels to mimic the
stem cell niche in vivo. Techniques have been developed to crosslink hydro-
gels while maintaining cell viability using various stimuli such as ions or
light [20, 21].
Biodegradable hydrogels that can respond to an external stimulus to facili-
tate cell migration, and ECM synthesis represents a promising direction for
musculoskeletal tissue engineering [22]. Lipase is an enzyme that catalyses
the degradation of ester bonds, hence this enzyme can be used to control the
degradation of ester-containing polymers [23]. The degradation rate of the
polymer can be controlled by the concentration of lipase or even the num-
ber of ester-cleavable bonds included in the monomer mix. Peptides that are
sensitive to cell-secreted proteases can also be incorporated into 3D scaffolds
to fabricate a biodegradable hydrogel network. Inclusion of protease degrad-
able sequences in a polymer will facilitate cell migration, which is critical for
many tissue regeneration processes. Lee et al. have developed a collagenase-
sensitive poly(ethylene glycol-co-peptide) diacrylate hydrogel that is suit-
able for cell migration, and a 3D pathway containing cell adhesive peptide
was fabricated using photolithography to promote cell migration in specific
directions [24]. Human dermal fibroblasts encapsulated within the hydro-
gel migrated only within the RGDS patterned region. Cell adhesive peptide
such as RGDS can also be incorporated into PEG-based hydrogels using a
thiol-acrylate mixed-mode polymerization technique [25]. This technique
involves the co-polymerization of monomers with thiol-reactive functional
groups such as cell recognizable peptide sequences, which are covalently
linked to the polymer network. The inclusion of this sequence was required
to increase the viability of cells encapsulated within the hydrogel. The hydro-
gels presented in both these studies study demonstrate a number of exciting