Biomedical Engineering Reference
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expression profile. Moreover, the researchers demonstrated peptide binding to
the BMP2-specific receptor [ 142 ]. The peptide was shown to induce prolonged
ectopic calcification when immobilized onto a covalently cross-linked alginate
gel and implanted into rat calf muscle, as compared to the full protein. These
results suggest that the peptide remained active at the implanted site, contin-
uously inducing the differentiation of osteoblast precursor cells into osteoblasts
and activating osteoblasts to promote ectopic calcification [ 144 ]. These results
were the basis for several additional experiments, indicating the potential of
this strategy in the induction of MSC osteogenic differentiation for bone repair
[ 144 - 146 ].
Other inductive BMP-derived peptides were identified and shown to be
effective for osteogenic differentiation, including peptides from BMP4 [ 147 ],
BMP7 [ 148 ] and BMP9 [ 149 ]. Recent studies indicate the beneficial effect of
material modification with a combination of the above-mentioned BMP-derived
peptide with the RGD adhesive peptide on the enhancement of MSC proliferation
and osteogenic differentiation [ 150 , 151 ].
Epitope Presentation Via Self-Assembling Peptide Scaffolds
Self-assembling peptides scaffolds have also been developed for the controlled
differentiation of stem cells through careful selection of the constituent peptides.
For example, Gelain et al. [ 112 ] attached several functional motifs including cell
adhesion, differentiation and bone marrow (BM) homing motifs to a self-assembling
peptide, and the functionalized peptides self-assembled into a nanofiber structure for
neural stem cell (NSC) cultivation. Specifically, peptide scaffolds containing BM
homing motifs significantly enhanced the neural cell survival without supplemen-
tation of extra soluble growth and neurotrophic factors to the routine cell culture
media. Moreover, the gene expression profile showed selective and more uniform
gene expression towards this cell lineage, compared with the control, Matrigel
scaffold [ 112 ]. In another study, Silva et al. [ 113 ] demonstrated that laminin-derived
isoleucine-lysine-valine-alanine-valine (IKVAV) peptide sequences could self-
assemble to form gels that selectively direct mouse neural progenitor cells toward a
neuronal fate [ 113 ].
3.2.2 Spatio-Temporal Presentation and Release of Signaling Molecules
Signaling molecules such as growth factors and cytokines are important for
gaining control over stem cell fate decision. These molecules can be added to the
culture media or secreted by the cells themselves. When exogenously supplied,
their activity may be affected by diffusion limitations within the 3D cultivation
system. Thus, current research is increasingly oriented towards presentation of
these signaling molecules in the context of the matrix, in a spatio-temporal
manner,
similar
to
their
presentation
by
the
native
ECM.
The
signaling
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