Scope of tissue engineering - Biomedical Engineering Desk Reference - page 675

and hepatocytes of the liver is comprised of distinctly
different collections of proteins including LN, type IV
collagen, and entactin. All ECMs share the common
features of providing structural support and serving as
a reservoir of growth factors and cytokines. The ECMs
present these factors efficiently to resident cell surface
receptors, protect the growth factors from degradation,
and modulate their synthesis. In this manner, the ECM
affects local concentrations and biological activity of
growth factors and cytokines and makes the ECM an
ideal scaffold for tissue repair and reconstruction.
The GAGs are also important components of ECM and
play important roles in binding of growth factors and cy-
tokines, water retention, and the gel properties of ECM.
The heparin binding properties of numerous cell surface
receptors and of many growth factors [e.g., fibroblast
growth factor (FGF) family, vascular endothelial growth
factor (VEGF)] make the heparin-rich GAGs extremely
desirable components of scaffolds for tissue repair. The
GAG components of the small intestine submucosa (SIS)
consist of the naturally occurring mixture of CSs A and B,
heparin, heparin sulfate, and HAc. To date it will need
time-consuming labor or much money to obtain a large
amount of purified components of the natural ECMs
and reconstruct an ECM from the purified components.
Since ECM plays an important role in a tissue's me-
chanical integrity, crosslinking of ECM may be an effec-
tive means of improving the mechanical properties of
tissues. The ECM crosslinking can result from the en-
zymatic activity of lysyl oxidase (LO), tissue trans-
glutaminase, or nonenzymatic glycation of protein by
reducing sugars. The LO is a copper-dependent amine
oxidase responsible for the formation of lysine-derived
crosslinks in connective tissue, particularly in collagen
and elastin. Desmosine, a product of LO-mediated
crosslinking of elastin, is commonly used as a biochemical
marker of ECM crosslinking. The LO-catalyzed cross-
links that are present in various connective tissues within
the bodydincluding bone, cartilage, skin, and lungdare
believed to be a major source of mechanical strength in
tissues. Additionally, the LO-mediated enzymatic re-
action renders crosslinked fibers less susceptive to pro-
teolytic degradation.

of tissues and organs, fulfilling some auxiliary functions,
especially improving comfort and the well-being of pa-
tients. Further possibilities exist now for synthetic ma-
terials to create tissues and organs with controlled
mechanical properties and well-defined biological be-
havior. In the biomaterial area, there are two kinds of
synthetic polymers, non-absorbable and absorbable.
Non-absorbable polymers have been used as key mate-
rials for artificial organs, implants, and other medical
devices. In most cases, absorbable polymers are not ad-
equate as the major component of permanent devices,
since absorption or degradation of materials in these
applications has a meaning almost identical to the ma-
terial deterioration which is an undesirable, negative
concept for biomaterials in permanent use. Widespread
clinical use of silicone, poly(ethylene terephthalate)
(PET), polyethylene, polytetrafluoroethylene (PTFE),
and poly(methyl methacrylate) (PMMA) as important
components of artificial organs and tissues is owing to the
excellent chemical stability or non-degradability in the
body. If these materials undergo degradation more or less
in the body, this will definitely raise a serious concern
because one cannot deny that degradation by-products
might evoke untoward reactions in the body. If these
stable polymers exhibit deterioration over time, this
might not always be due to hydrolysis but due to attack
by active oxygens generated in the body as a result of
inflammation.
For simplicity, bioabsorbable, synthetic polymers are
here classified into three groups: poly(a-hydroxyacid)s,
synthetic hydrogels, and others.

7.2.2.2.1 Poly(a-hydroxyacid)s [aliphatic
a-polyesters or poly(a-hydroxyester)s]
The majority of bioabsorbable, synthetic polymers that
are currently available is poly(a-hydroxyacid)s that have
repeating units of-O-R-CO- (R: aliphatic) in the main
chain. This is mainly because most of them have the
potential to produce scaffolds with sufficient mechanical
properties and some of them have been approved by the
U.S. FDA for a variety of clinical applications as absorb-
able biomaterials with biosafe degradation by-products.
By contrast, aromatic polyesters with phenyl groups in
the main chain do not undergo any appreciable degra-
dation in physiological conditions. The monomers used
for synthesis of poly(a-hydroxyacid)s include glycolic
acid (or glycolide), and L - and DL -lactic acid (or L - and DL -
lactide) with a hydroxyl group on the a carbon. These
monomers can yield not only homopolymers but also
copolymers when polymerized together with other
monomers such as 3-caprolactone (CL), p-dioxanone,
and 1,3-trimethylene carbonate (TMC). Chemical
structures of a-hydroxyacid polymers, copolymers, and
their monomers are shown in Fig. 7.2-7 .

7.2.2.2 Synthetic polymers

Before the prion shock, naturally derived materials had
attracted much attention because of their natural origin
which seemed to guarantee the biocompatibility. How-
ever, reports on the Creutsfeld-Jacobs disease due to
the implanted sheets made from human dried dura
mater diverted the focus of biomaterial scientists to non-
biological materials such as synthetic polymers. Syn-
thetic materials have long been applied for replacements