STEM CELLS AND NANOTECHNOLOGY IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 17

Additionally, it may be desirable to have fibers of different dimensions or mechanical
properties within the same scaffold. This has led to the development of multi-jet
electrospinning in which different polymer solutions can either be electrospun at
thesametimetogenerateahomogeneous mixed scaffold or sequentially to
generate a layered scaffold. 111 Baker et al. co-electrospun three different solutions
containing polymers with varying degradation rates and mechanical properties to
develop a scaffold that allowed for both improved cellular infiltration by increas-
ing pore size as well as more closely mimicked the properties of the native
tissue. 112
Electrospinning is a relatively simple, cost-effective technique that has shown
significant potential in studies aimed at repair of many different types of tissues.
When seeded with stem cells, nanofiber scaffolds have been shown to enhance
differentiation toward many different cell types, including bone, cartilage, cardiac
and skeletal muscle, blood vessels, and nerve. 113,114

1.4.5 Growth Factor Delivery

Although the scaffold structure plays an essential role in controlling cell behavior,
chemical or biological modulators of cell activity and phenotype heavily influence
tissue formation both in vitro and in vivo. In native tissues, growth factors provide
specific signals to cells that direct cell activities, including cell migration, prolifera-
tion, and differentiation. The effects of growth factors are quite complex and are
dependent on the concentration of the growth factor, phenotype of the cells acted on
by the growth factor, and functional characteristics of the specific cell receptor
interacting with the growth factor.
In vitro tissue engineering studies often supply relevant growth factors in the
culture medium to induce cellular differentiation. However, because most growth
factors have very short half-lives, in order to maintain long-term signaling when
tissue engineered constructs are implanted in vivo, it is important to develop a
delivery system that can provide sufficient concentrations of specific factors over the
desired period of time, preferably at specified rates. Nanoscale techniques for growth
factor delivery have typically focused on two basic methods: (1) immobilization of
the growth factor on the surface of a substrate or (2) encapsulation of the growth
factor within a degradable delivery system.
Growth factors can be immobilized onto a material surface through either
physical adsorption or through covalent linkage. Although simple physical adsorp-
tion is limited in its effectiveness because of competition by other proteins with
higher affinity for the polymer, 115 successful noncovalent adsorption onto a nano-
material has been accomplished by mixing heparin into a synthetic polymer solution
that is then electrospun into nanofibers. Heparin is a sulfated glycosaminoglycan that
has a strong affinity for a number of growth factors, including basic fibroblast growth
factor (bFGF), epidermal growth factor (EGF), vascular endothelial growth factor
(VEGF), and transforming growth factor- ). In one study, low-molecular-

weight heparin was conjugated to a poly(ethylene glycol) (PEG) carrier and
electrospun with either PEO or poly(lactide-co-glycolide) followed by successful

b (TGF- b