Biomedical Engineering Reference
In-Depth Information
the presence of cations enables guluronic acid
residues of adjacent chains to cross-link. The
elastic compressive and shear moduli of algi-
nate gels increase with increasing concentra-
tion of alginate, which allows specifi c materials
to be designed for various applications. For
example, varying the concentration of alginate
from
pared with chitosan fi bers. Additionally, an in
vitro culture using rabbit chondrocytes found
signifi cantly higher cell adhesivity, cell prolif-
eration, and synthesis of aggrecan on hybrid
polymer fi bers than on chitosan fi bers alone
[
62
,
105
,
107
].
% (w/v) leads to an increase in the
equilibrium compressive modulus from
1
% to
3
4.5.1.4 Fibrin
Fibrin is a natural biomaterial formed in the
process of wound healing, resulting from the
cleavage of fi brinogen molecules by thrombin
to form fi brin. Fibrin monomers are then
assembled into fi brils, eventually forming fi bers
in a three-dimensional network (a fi brin clot).
The fi brin clot enhances fi broblast infi ltration
and encourages proliferation necessary for the
healing process [
0
.
9
to
8
]. The ratio of mannuronic acid to gulu-
ronic acid also affects gel properties, such as
biocompatibility and gel porosity [
kPA [
9
]. This
type of hydrogel has been employed to encap-
sulate chondrocytes and has demonstrated
phenotype retention through maintenance of
the cell's spherical morphology [
22
].
Chitosan is a positively charged polysaccha-
ride derived from chitin, a protein found in
insect and crustacean shells. Chitosan is
degraded in vivo by the action of lysozyme, and
the rate of degradation is affected by the amount
of residual acetyl content [
58
,
97
]. Unlike the above-men-
tioned natural materials, fi brin is not made up
of ECM molecules. However, the possibility of
its use in orthopedic tissue-engineering scaf-
folds has recently been widely examined, since
fi brin not only is biocompatible and biodegrad-
able, but also is easily formed simply by com-
bining two components, fi brinogen
34
,
76
]. Chemical modi-
fi cation imparts a variety of physical and bio-
logical properties [
76
]. Many derivatives of
chitosan have been developed to overcome
insolubility problems caused by high material
crystallinity. Chitosan has also been modifi ed
to enhance cellular interactions for tissue-
engineering applications [
9
,
62
and
thrombin [
]. An in vivo study found that
porcine chondrocytes produced cartilage when
implanted with a fi brin polymer, whereas cells
implanted alone did not produce any cartilage
[
34
]. Because there is
no interspecies variation in terms of the chemi-
cal and physical structure of chitosan, regula-
tion and quality assurance of this material is
greatly simplifi ed [
62
53
].
4.5.2 Synthetic Materials
].
Hyaluronic acid (HA), also called hyaluro-
nan, is an anionic polysaccharide composed of
repeating disaccharide units of N-acetylglucos-
amine and glucuronic acid. HA, a major com-
ponent of cartilage ECM, has several advantages
for use as a biomaterial. It is easy to isolate, can
be chemically modifi ed, and does not evoke a
signifi cant immune response [
63
,
88
Synthetic biomaterials have many advantages
over natural materials. They can be synthe-
sized in controlled environments to regulate
such properties as molecular weight and molec-
ular weight distribution. This characteristic
leads to better batch-to-batch uniformity than
is possible with the use of natural materials,
while retaining the fl exibility to tailor material
properties for a given application. Several
synthetic biomaterials have been used for
orthopedic implants, including poly(
]. Further-
more, in vitro studies with HA show that the
material encourages chondrocyte proliferation
and ECM production [
76
].
Although each of these natural polysaccha-
ride materials holds promise for orthopedic
applications, none is strong enough to be used
as the only material at load-bearing sites. Thus,
these materials are often combined with other
natural or synthetic materials in a composite to
improve the mechanical properties of the
implant. For example, a study using chitosan-
hyaluronic acid hybrid polymer fi bers found a
signifi cant increase in tensile strength as com-
29
α
-hydroxy
esters), poly(
-caprolactone), poly(orthoesters),
poly(anhydrides), PEG-based materials, poly
(amino acids), and fumarate-based materials.
These are described individually below.
ε
4.5.2.1 Poly(
a
-Hydroxy Esters)
Poly(
-hydroxy esters), including poly(glycolic
acid) (PGA) and poly(lactic acid) (PLA), have
been widely investigated as tissue-engineering
α
