Biomedical Engineering Reference
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strain) scaffolds, as measured by collagen types I and III and tenascin-C. The
scaffolds which underwent both uniaxial strain culture and initially contained
500 ng of bFGF resulted in the highest expression of collagen types I and III and
tenascin-C mRNA. In addition, histology also showed that either the inclusion of
bFGF or strain caused BMSCs to elongate, but there was no additive or
synergistic effect on cell morphology with the two combined. In Farng
et al.
,
GDF-5 was used to determine whether the growth factor and mechanical
stimulation would influence cellular differentiation and proliferation on the PCL
scaffolds using a mouse bone marrow stromal cell line [134]. Neither mechanical
strain nor GDF-5 alone increased cell proliferation, but when combined, cell
activity was 1.7 times greater than the untreated (no strain, no GDF-5) controls.
However, the combination of GDF-5 and strain only produced an increase in the
expression of collagen III mRNA, while the stimuli alone caused collagen I and
scleraxis mRNA to also be upregulated. It is clear that chemical signals or
mechanical strain alone could aid in the creation of a tissue engineered ligament
construct, but there is still potential for optimization of the combination of both
stimuli.
To enhance initial cell-matrix interactions with a ligament scaffold, Chen
et al.
modified a silk fibroin material with the RGD peptide [135]. The silk
protein material, when prepared as a wire-rope matrix, had been characterized as
a suitable scaffold for ligament tissue engineering due to its physiologically
applicable mechanical properties that can be maintained
in vitro
, and the fact
that, after it is implanted, it will degrade slowly [136]. It can be modified
by covalent coupling of RGD peptides by activation with 1-ethyl-3-
(dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-
hydroxysuccinimide (NHS), followed by incubation with the peptide solution.
These scaffolds were cultured in a bioreactor system which provides a suitable
environment for construct growth as well as applying mechanical stimulation
with both linear and rotational displacement [137]. When cultured with human
bone marrow stromal cells (BMSC), the silk matrices exhibited a higher cell
density and enhanced cell spreading when modified with the peptide, both 1 hour
and 1 day after seeding, but the peptide did not appear to influence cell growth
rates from 7 to 14 days of culture. Collagen type I was produced significantly
more in RGD-modified matrices after 14 days of culture, and collagen
transcription levels at day 7 were elevated on the modified matrices. However,
these are not entirely conclusive evidence of the differentiation lineage of the
BMSCs, as these are also typical of the fibroblastic phenotype. Overall, the
incorporation of a peptide known to enhance cell adhesion and migration seemed
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