Biomedical Engineering Reference
In-Depth Information
the form of a porous sponge. MSCs seeded on these materials have increased ECM
gene expression and protein deposition both in vitro and after in vivo implantation
in rabbit patellar and Achilles tendon [ 97 - 99 ]. However, collagen fibers acquired
from animals must be processed to remove foreign pathogens to minimize disease
transmission [ 91 ]. Collagen can also easily be degraded, which causes the matrix to
rapidly lose mechanical strength [ 91 , 100 ]. Crosslinking can slow down the process
of degradation and the rate of mechanical property loss. However, this technique
can introduce potential toxic residues in the form of crosslinking agents [ 91 ].
Silk, a protein fiber from silkworms, can also be used as a naturally derived
scaffold for tendon and ligament tissue engineering. Silk is composed of a fibroin
core and a glue-like sericin cover. Silk fibers have high Young's modulus values
when compared to PLA and collagen [ 101 ] and undergo relatively slow proteolytic
degradation in vivo [ 27 ]. However, over long periods of time, degradation is
mediated by a foreign body response. In one study, 12 weeks after silk was
implanted in the abdomen wall of a rabbit, tensile strength of the fibers decreased
80% from their original value and histology revealed a decrease in number of fibers
over 2 years [ 102 ]. While the mechanical properties of silk are promising, there is a
concern of the potential negative immune response because it is not a native
material found in the body [ 79 , 91 ].
15.4.3 Exogenous Factors
A number of biochemical and mechanical signals can be used to manipulate cell
and scaffold interactions for fibrous tissue engineering. Various exogenous factors
have been identified that improve tendon and ligament cell proliferation and matrix
formation in vitro and in vivo [ 8 ], which could be harnessed to improve production
of engineered tendon/ligaments in vivo or ex vivo . This section discusses both
soluble factors (i.e., growth factors) that improve cellular response and the use of
bioreactors to create controlled culture systems for tissue-engineered cell and
scaffold constructs. Soluble Factors
, platelet-derived growth factor (PDGF), bFGF, and insulin-like growth
factor-1(IGF-1) have all shown to upregulate fibroblast proliferation and ECM
production [ 73 , 103 , 104 ].
TGF- b : TGF-
increases collagen and proteoglycan gene expression and synthesis
in fibroblasts [ 105 - 107 ]. In vitro studies have examined the effects of the introduc-
tion of TGF-
1 at different concentrations (0.12-25 ng/mL) in culture media [ 72 ].
Human dermal fibroblasts showed a significant increase in gene expression of
collagen type III after 3 days [ 72 ]. In another study, proteoglycan production
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