Scope of tissue engineering - Biomedical Engineering Desk Reference - page 680

porous structure. This issue has led some investigators to
fabrication of composites from inorganic and organic
materials. A well-known example is a composite from
HAp and soft collagen, which is a biomimetic from
a compositional point of view. Owing to its pliability one
can trim the porous composite with scissors into a de-
sired shape.
The PLA, PGA, and some other synthetic polymers
have an established safety record in humans, but are not
osteoconductive. Apatite-coated polymer composites
combine the osteoconductive property of bioceramics
and the mechanical resilience of organic polymers.
Polymeric scaffolds impregnated with apatite promote
in vitro cellular attachment and bone nodule formation,
as well as bone formation in vivo, providing an appro-
priate osteogenic environment for tissue engineering.
Such bioabsorbable and bioactive composites have been
developed, combining resorbable polymers with calcium
phosphates, bioactive glasses, or glass-ceramics in various
scaffold architectures. Besides imparting bioactivity to
a polymer scaffold, the addition of bioactive phases to
bioabsorbable polymer may alter polymer degradation
behavior. Bioactive phases in bioabsorbable polymer
allow rapid exchange of protons in water for alkali in the
glass or ceramic, which may provide a pH buffering
effect at the polymer surface, reducing acceleration of
acidic degradation products from the polymer. A further
advantage of using bioactive inorganic particles for com-
posite preparation with absorbable polymers is increased
mechanical properties owing to the filler effect.

of cells as well as cell adhesion and matrix deposition
varies with different cell types. Generally, the optimal
pore size ranges from 100 to 500 m m and the optimal
porosity is above 90%. Various bone engineering groups
have noted that pore sizes of greater than 300 m m have
a greater penetration of mineralized tissue in comparison
with smaller pore sizes, while at pore sizes of 75 m m,
hardly any mineralized tissue is found within the scaf-
fold. High porosity enables maximal conversion of cells
and tissue invasion necessary for construction, together
with conduits suitable for blood vessel formation.
Scaffolds of hydrogel type such as collagen gel and
fibrin glue have no geometrical pores recognizable with
SEM, but nutrients and oxygen are delivered to cells via
physical diffusion through the aqueous medium. The
term ''channel'' may be more appropriate for character-
izing the pore structure, because interconnected pores
form a channel. However, fabrication of scaffolds with
typical channel structures is extremely tedious [5] .
A variety of techniques have been developed to fab-
ricate porous scaffolds, of which some include woven and
non-woven fiber-based fabrics, solvent casting, salt (or
particulate) leaching, temperature-induced phase sepa-
ration, gas foaming with pressurized carbon dioxide, melt
molding, high-pressure processing, membrane lamina-
tion, forging, injection molding, pressing, inkjet printing,
fused deposition modeling, electrospinning, rapid
prototyping, among others. A simple method is to use
absorbable fibers as a starting material, because fibers can
yield a variety of ''porous'' products including woven or
knitted cloth, non-woven fabric, web, mesh, felt, and
fleece. Conventional spinning can produce either multi-
filaments or monofilaments. A representative example is
products from PGA which has very few specific solvents
but readily yields fibers by melt spinning. To produce
aggregates of PGA fine fibers by means of electro-
spinning, we need expensive solvents such as trifluor-
opropyl alcohol for preparing the stock solution for
electrospinning of PGA.
Another simple method available in small labs for
porous scaffold fabrication is to use the solution of ab-
sorbable polymers. One can readily obtain a porous sheet
or a 3-D block when a polymer solution is subjected to
freeze drying. When a polymer solution is mixed with
porogens such as NaCl particulates followed by drying
and removal of the porogens from the dried material, we
obtain a porous scaffold with the pore size determined
by the particulate size. Supercritical liquids have also
been applied to fabrication of porous materials. More
sophisticated methods applied for scaffold formation
are imprinting of polymers and photo-polymerization
of monomers along with computer-aided machines.
The 3-D printing is a novel technique and the application
of this technique for tissue engineering is still limited.
These modern technologies, together with computer

7.2.3 Pore creation in biomaterials

The 3-D architecture of scaffolds with proper pore size,
pore shape, alignment, and interconnectivity can have
significant effects on regulating the tissue-specific mor-
phogenesis of cultured cells. The rate of tissue ingrowth
increases as the porosity and the pore size of the
implanted devices increase. The transport of molecules
through pores is a function of their size, connectivity, and
tortuosity. Thus, the architecture of scaffolds will sig-
nificantly affect nutrient and oxygen transport within the
3-D matrix, which may directly affect the cell motility
during tissue regeneration. The porous structure of
scaffold is characterized by two parameters, pore size and
porosity. The average pore diameter must be large
enough for cells to migrate through the pores and small
enough to retain a critical total surface area for appro-
priate cell binding. To allow for transport of cells and
metabolites the scaffold must have a high specific surface
and large pore volume fraction in addition to an inter-
connected pore network. Scaffold pore size has been
shown to influence cell adhesion, growth, and phenotype.
The optimal scaffold pore size that allows maximal entry