Tissue engineering - Biomedical Engineering Desk Reference - page 655

limited to tubular scaffolds with a low ratio of wall
thickness to inner diameter.
To increase the pliability of the porous membranes,
PEG has been blended with PLGA in the SC/PC process
( Wake et al. , 1996 ). Micropores resulted from dissolu-
tion of PEG during leaching are believed to alter the
structure of the pore walls and increase the pliability of
the scaffold. These membranes can be rolled over into
tubular scaffolds with a significantly higher ratio of wall
thickness to inner diameter. The membranes fabricated
from the polymer blend do not show any macroscopic
damage during rolling as is observed for tubes made of
PLGA alone.
Highly porous PPF scaffolds have also been formed
using the SC/PL technique for both tissue induction and
delivery of bioactive factors ( Fisher et al. , 2003; Hedberg
et al. , 2002 ). In this procedure, the PPF is cross-linked
around the salt particles in molds of desired size. The
samples are then removed from the molds and the salt is
leached in water. Mechanical and degradation properties
of the resulting scaffolds, with pore sizes ranging from
300 to 800 m m and porosities of 60-70%, have been
characterized in vitro ( Fisher et al. , 2003 ). These scaf-
folds were also found to induce a mild tissue response
when implanted for up to 8 weeks either subcutaneously
or in cranial defects in rabbits ( Fisher et al. , 2002 ).

Compression molding

Compression molding is an alternative technique of
constructing 3D scaffolds. In this method, a mixture of
fine PLGA powder and gelatin microspheres is loaded in
a Teflon mold and then heated above the glass transition
temperature of the polymer ( Thomson et al. , 1995 ). The
PLGA/gelatin composite is subsequently removed from
the mold and gelatin microspheres are leached out. In
this way, porous PLGA scaffolds with a geometry iden-
tical to the shape of the mold can be produced.
Polymer scaffolds of various shapes can be constructed
by simply changing the mold geometry. This method also
offers the independent control of porosity and pore size
by varying the amount and size of porogen used, re-
spectively. In addition, it is possible to incorporate
bioactive molecules in either polymer or porogen for con-
trolled delivery, because this process does not utilize
organic solvents and is carried out at relatively low
temperatures for amorphous PLGA scaffolds. This
manufacturing technique may also be applied to PLA or
PGA. However, higher temperatures are required (above
the polymer melting temperatures) because these poly-
mers are semicrystalline.
Compression molding can be combined with the SC/
PL technique to form porous 3D foams. The dried PLGA/
salt composites obtained by SC are broken into pieces of
less than 5 mm in edge length and compression-molded
into a desired 3D shape ( Widmer et al. ,1998 ). The
resulted composite material can then be cut into desired
thickness. Subsequent leaching of the salt leaves an open-
cell porous foam, with more uniform pore distribution
than those obtained by SC/PL for increased thickness.
Highly porous poly(a-hydroxy ester) scaffolds, though
desirable in many tissue engineering applications, may
lack required mechanical strength for the replacement of
load bearing tissues such as bone. Hydroxyapatite and
b-tricalcium phosphate are biocompatible and osteo-
conductive materials and can be incorporated into these
foams to improve their mechanical properties. Because the
macroscopic mixing of three solid particulates (polymer
powder, porogen, and ceramic) is difficult, a combined SC,
compression-molding, and PL technique described earlier
has been employed to fabricate an isotropic composite
foam scaffold of PLGA reinforced with short hydroxyap-
atite fibers (15 m m in diameter and 45 m minlength)
( Thomson et al. , 1998 ). Within certain range of fiber con-
tents, these scaffolds have superior compressive strength
compared to nonreinforced materials of the same porosity.

Superstructure engineering

Polymer scaffolds with complex 3D architecture (su-
perstructures) can be formed by superimposing defined
structural elements such as pores, fibers, or membranes
in order according to stochastic, fractal, or periodic
principles ( Wintermantel et al. , 1996 ). This approach
may provide optimal spatial organization and nutritional
conditions for cells. The coherence of structural ele-
ments determines the anisotropic structural behavior of
the scaffold. The major concern in engineering super-
structures is the spatial organization of the elements in
order to obtain desired pore sizes and interconnected
pore structure.
A simple example of this technique is membrane
lamination to construct foams with precise anatomical
shapes ( Mikos et al. , 1993b ). A contour plot of the par-
ticular 3D shape is first prepared. Highly porous PLA or
PLGA membranes with the shapes of the contour are
then manufactured using SC/PL. The adjacent mem-
branes are bonded together by coating chloroform on their
contacting surfaces. The final scaffold is thus formed
by laminating the constituent membranes in the proper
order. It has been shown that continuous pore structures
are formed with no boundary between adjacent layers. In
addition, the bulk properties of the 3D scaffold are
identical to those of the individual membranes.

Extrusion

Various extrusion methods such as ram (piston-cylinder)
extrusion, hydrostatic extrusion, or solid-state-extrusion