STEM CELLS AND NANOTECHNOLOGY IN TISSUE ENGINEERING AND REGENERATIVE MEDICINE - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 16

collagen, 87-90 elastin, 87,91 silk fibroin, 92-94 dextran, 95 and chitosan. 96,97 Because the
synthetic polymers typically used in electrospinning are hydrophobic and lack
biologically active functional groups, they are often modified either physically or
chemically after the electrospinning process to increase their hydrophilicity and
ability to interact with cells and biomolecules.
Plasma treatment, similar to that performed on tissue-culture polystyrene, can
generate functional carboxyl or amine groups on the surface of the fibers. This has
been shown to enhance cell attachment and proliferation either alone 98,99 or via the
coating of the functionalized fiber with a natural ECM protein such as collagen 100,101
or gelatin. 102 Wet chemical etching methods may provide more homogeneous
functionalization in thicker scaffolds because plasma etching can only penetrate
the outer surface of a thicker scaffold. This method typically involves NaOH
hydrolysis or aminolysis of the polymer, breaking the ester bond at random points
and creating a hydroxyl or amino group, respectively. 103 One study demonstrated
that esophageal epithelial cells seeded on aminolyzed poly( L -lactide-co-caprolac-
tone)(PLCL) coated with fibronectin exhibited higher collagen type IV synthesis
than those seeded on the unmodified polymer, suggesting that this method may be
useful in tissue engineering studies. 104
Composite scaffolds formed from co-electrospinning of different polymers have
been used to control the mechanical as well as structural properties of the scaffold.
Perhaps the biggest challenge using the electrospinning method is that the pore size is
typically much smaller than the diameter of a typical cell, a property that makes cell
and nutrient infiltration into the middle of the scaffold difficult. Several methods
have been used to overcome this problem, including spinning of mixed microfiber
and nanofibers scaffolds, 105 as well as using water-soluble polymers (i.e., poly-
ethylene oxide [PEO]) in combination with slower-degrading materials (i.e., PCL),
that can be quickly dissolved after spinning, leaving the nonsoluble, slower-
degrading polymer behind with larger pore sizes. 106-108
To more closely tailor the properties of a scaffold—including biologic, mechani-
cal, and degradation characteristics—researchers have begun to combine two or
more different components within a single scaffold. This can be done before
electrospinning by mixing several polymers within a single solution, which results
in a single fiber containing each component or by electrospinning multiple
solutions of polymers onto the same collector, thereby creating a scaffold with
multiple fiber types.
Although natural polymer scaffolds composed of ECM proteins such as collagen
and elastin show increased cellular response, when used alone, they lack sufficient
mechanical properties to function in the in vivo setting. Combining ECM derived
from urinary bladder matrix with poly(ester-urethane)urea, Stankus et al. were able
to develop electrospun scaffolds with improved mechanical and biological properties
than possible using the individual polymers alone. 109 Similarly, Lee et al. mixed
collagen and elastin with several biodegradable synthetic polymers to develop
scaffolds to use as vascular grafts. 110
Some polymers cannot be dissolved in the same solvent, therefore limiting the
options for combining several different polymers within the same solution.