Biomaterials for Cell-Based Therapeutic Angiogenesis - Mechanical and Chemical Signaling in Angiogenesis - page 247

Fig. 3 Schematic illustration of blood vessel formation mediated by seeding endothelial cells into a
porous scaffold (a). Transplanted endothelial cells develop new blood vessels within the scaffold
that grow towards host vasculature (b). Ultimately, host vasculature connects with new vasculature
in order to form mature and functional blood vessels capable of carrying blood (c)[ 33 ]
15 mm hole was created on the back of athymic mice and the scaffold was placed
over the wound. Wound healing was significantly improved by incorporating the
drug-releasing cells into the scaffold, as seen with increased neovascular regen-
eration, when compared to the scaffold alone. In vitro studies indicated that the
stable values of VEGF secreted into the media ranged from 1.5 to 2.1 ng/mL while
bFGF stabilized at 0.2 ng/mL [ 14 ]. While this result is impressive, it is technically
challenging to tune the cellular production of VEGF or FGF in terms of amount
and sustainability.
2.2 Microfiber Scaffolds
Microfibrous scaffolds are also used in cell-based revascularization therapies,
because of their structural similarity to natural ECM. The fibrous structure of ECM
is known to facilitate cell adhesion and also mass transport through a three
dimensional matrix [ 15 ]. In native ECM, these fibers are typically formed from
self-assembly between collagen and fibrin fibrils [ 15 ]. To mimic these structures,
nano or microfibrous scaffolds are fabricated by electrospinning various biode-
gradable polymers including poly(L-lactic acid) and their copolymers to a sub-
strate (Figs. 4 and 5 )[ 15 ]. The diameter of resulting fiber ranges from 3 nm to
6 lm, depending on chemical structure of polymers and processing condition [ 16 ].
In addition, the resulting fibrous scaffolds exhibit the mechanical rigidity and
fracture resistance superior to natural ECM [ 16 ].
Early studies have demonstrated that collagen-based microfiber scaffolds can be
used to develop small diamater (\6 mm) blood vessels consisting of an endothelial
lining and a smooth muscle layer. In this study, smooth muscle cells were plated onto
a fibrous scaffold composed of collagen fibers and poly(lactic acid) (PLA) fibers. The
scaffold was fabricated by placing collagen fibers on a stainless steel mandrel and
then electrospinning PLA fibers on top of the collagen fibers. The collagen fibers
were used to emulate the stress environment found in arteries. The PLA fiber mesh is
designed to provide initial structure and as a place to seed the smooth muscle cells.
Following 10 days of culture in vitro, smooth muscle cells adhered to the fibrous
scaffold displayed a spindle shape and also alligned along the collagen fibers [ 17 ].