STRATEGIES TO ENGINEER ELECTROSPUN SCAFFOLD ARCHITECTURE AND FUNCTION - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 296

15.3 Creation of Larger Pores to Facilitate
Cell Entry into Scaffolds

One shortcoming of electrospun meshes is that cells seeded on
their surfaces do not readily migrate into the interior. 37 , 38 This lim-
itation has been attributed to the very small gaps between fibers
through which the cells must pass, and while it may be mitigated by
increasing the diameter of the electrospun fibers, 38 this can negate
intrinsicadvantagesofusingnanofibersovermicrofibers(e.g.,topo-
graphic features to guide spreading, cell alignment, and expression
of phenotypic markers). Therefore, several alternative strategies
have been tested to enlarge the spaces between electrospun fibers
in order to better permit cell migration into electrospun meshes,
including 1) co-electrospinning, 2) combining electrospun fibers
with larger extruded fibers, and 3) incorporating a porogen into
scaffolds.

15.3.1 Co-Electrospinning of a Sacrificial Polymer
Co-electrospinning of two polymers from separate spinnerets has
been examined by many groups as a means to increase cell pene-
tration. Typically, one polymer is water soluble (e.g., gelatin, poly-
ethylene oxide [PEO]) and is intended to dissolve away to reveal
larger spaces between remaining fibers. Results with this approach
have been modest. Baker et al. 37 using PEO to form sacrificial fibers
found good cell infiltration into 0.8 mm thick scaffolds when the
PEO content was greater than 50 wt% but showed that the resul-
tant scaffolds could collapse in cell culture. In contrast, Ekaputra
et al. 38 reportedonlymodestimprovementsincellpenetrationwith
co-electrospinning of PEO or gelatin sacrificial fibers. Indeed, they
observed better cell penetration when they neglected the sacrificial
polymer and simply increased the diameter of their fibers from 0.5
to 1.3

μ

m.

15.3.2 Incorporation of Extruded Fibers
The combination of large fibers with electrospun nanofibers also
has been examined as a means to increase pore size and cell