Biomedical Engineering Reference
In-Depth Information
gene expression of the cells thereby affecting degradation of the tissue and the ECM
synthesis of cells. They can also influence secretion and activation of other growth
factors. Effects of growth factors depend on the concentration. Newgeneration strate-
gies incorporate also growth factors into the tissue engineering constructs to promote
the regeneration. Frequently employed growth factors for cartilage or bone tissue en-
gineering include bone morphogenetic proteins (BMPs), insulin-like growth factors
(IGFs), transforming growth factor-
), fibroblastic growth factors (FGFs),
and platelet-derived growth factor (PDGF). For example, insulin-like growth factor-
1 is the main anabolic growth factor for cartilage; it has effects on stimulation of
synthesis and inhibits the breakdown of PGs and cartilage homeostasis. Also, it may
improve the tissue integration and decrease the synovial inflammation in vivo [
85
].
Fortier et al. [
86
] showed in a horse model that IGF-1 introduced to chondrocyte-
fibrin grafts may facilitate the repair process of the full thickness defects.
Lieberman et al. [
84
] and Linkhart et al. [
87
] reviewed the use of growth factors
for bone repair. Fortier et al. [
88
] reviewed the role of growth factors for cartilage
tissue regeneration, and their effects on MSCs. Each growth factor affects the cell
and the tissue in a specific way; however, the cumulative effects of growth factors
are still poorly understood, and should be further investigated since their adequate
combination is a must for appropriate tissue regeneration.
Bioreactors
are devices that can control the culture media conditions such as the
temperature, pH, oxygen ratio, osmolality and nutrients, and thereby can facilitate
more advanced tissue regeneration in vitro. They can also promote uniform cell seed-
ing, and facilitate the mass transfer between the culture and the cells. Moreover, with
bioreactors it can be possible to have interstitial fluid flow, or mechanical stimulation
such as pressure and compression [
89
]. Various bioreactors have been developed for
tissue engineering purposes. For example: (i) spinner flasks [
90
] are simple biore-
actors for cell seeding onto scaffolds where turbulent dynamic flow of medium is
generated by amagnetic stirrer; (ii) rotatingwall vessels [
91
] aremade of horizontally
rotating cylinders filled with culture medium, and provide low-turbulence laminar
dynamic flow as well as adequate oxygenation; (iii) flow perfusion bioreactors [
92
]
have a system that can continuously provide direct flow of culture medium through
the porous structure of the scaffold and in this way enhance the mass transfer to the
interior of the scaffold; and (iv) bioreactors that provide mechanical loading have
been developed since it is known that cartilage and bone tissues are affected by me-
chanical loading. For example, Pei et al. [
93
] used a bioreactor that can provide a
mechanically active environment with efficiently mixed media, low velocity laminar
flow and shear stress. They showed that this kind of bioreactor can enhance the struc-
tural, functional and molecular properties of in vitro-generated cartilage compared
to the use of Petri dishes [
93
].
β
(TGF-
β
2.4.2 Strategies for Tissue Regeneration
One of the two routes [
10
] that can be followed for tissue regeneration is implanting
the cells and scaffolds into the lesion site for enhancing the regeneration process
