Biomedical Engineering Reference
In-Depth Information
conventional poly(amino acids) can be traced to the re-
duction in the number of interchain hydrogen bonds: In
conventional poly(amino acids), individual amino acids
are polymerized via repeated amide bonds leading to
strong interchain hydrogen bonding. In natural peptides,
hydrogen bonding is one of the interactions leading to the
spontaneous formation of secondary structures such as a-
helices or b-pleated sheets. Strong hydrogen bonding also
results in high processing temperatures and low solubility
in organic solvents which tends to lead to intractable
polymers with limited applications. In ''pseudo''-poly-
(amino acids), half on the amide bonds are replaced by
other linkages (such as carbonate, ester, or iminocar-
bonate bonds) that have a much lower tendency to form
interchain
PGA and PLA and their copolymers are currently
the most widely investigated, and most commonly used
synthetic, bioerodible polymers. In view of their impor-
tance in the field of biomaterials, their properties and
applications will be described in more detail.
PGA is the simplest linear, aliphatic polyester
(Fig. 3.2.7-1
). Since PGA is highly crystalline, it has
a high melting point and low solubility in organic sol-
vents. PGA was used in the development of the first
totally synthetic, absorbable suture. PGA sutures have
been commercially available under the trade name
''Dexon'' since 1970. A practical limitation of Dexon
sutures is that they tend to lose their mechanical strength
rapidly, typically over a period of 2 to 4 weeks after im-
plantation. PGA has also been used in the design of in-
ternal bone fixation devices (bone pins). These pins have
become commercially available under the trade name
''Biofix.''
In order to adapt the materials properties of PGA to
a wider range of possible applications, copolymers of
PGA with the more hydrophobic PLA were intensively
investigated (
Gilding and Reed, 1979, 1981
). The hy-
drophobicity of PLA limits the water uptake of thin
films to about 2% and reduces the rate of backbone
hydrolysis as compared to PGA. Copolymers of
glycolic acid and lactic acid have been developed as
alternative sutures (trade names ''Vicryl'' and ''Poly-
glactin 910'').
It is noteworthy that there is no linear relationship
between the ratio of glycolic acid to lactic acid and the
physicomechanical properties of the corresponding co-
polymers. Whereas PGA is highly crystalline, crystal-
linity is rapidly lost in copolymers of glycolic acid and
lactic acid. These morphological changes lead to an in-
crease in the rates of hydration and hydrolysis. Thus,
50:50 copolymers degrade more rapidly than either
PGA or PLA.
Since lactic acid is a chiral molecule, it exists in two
steroisomeric forms that give rise to four morphologically
distinct polymers: the two stereoregular polymers,
D
-PLA and
L
-PLA, and the racemic form
D
,
L
-PLA. A
fourth morphological form,
meso
-PLA can be obtained
from
D
,
L
-lactide but is rarely used in practice.
The polymers derived from the optically active
D
and
L
monomers are semicrystalline materials, while the opti-
cally inactive
D
,
L
-PLA is always amorphous. Generally,
L
-
PLA is more frequently employed than
D
-PLA, since the
hydrolysis of
L
-PLA yields
L
(
รพ
)-lactic acid, which is the
naturally occurring stereoisomer of lactic acid.
The differences in the crystallinity of
D
,
L
-PLA and
L
-
PLA have important practical ramifications: Since
D
,
L
-
PLA is an amorphous polymer, it is usually considered for
applications such as drug delivery, where it is important
to have a homogeneous dispersion of the active species
within
hydrogen
bonds,
leading
to
better
pro-
cessibility and, generally, a loss of crystallinity.
Polycyanoacrylates are used as bioadhesives. Methyl
cyanoacrylates are more commonly used as general-
purpose glues and are commercially available as ''Crazy
Glue.'' Methyl cyanoacrylate was used during the
Vietnam war as an emergency tissue adhesive, but is no
longer used today. Butyl cyanoacrylate is approved in
Canada and Europe as a dental adhesive. Cyanoacrylates
undergo spontaneous polymerization at room tempera-
ture in the presence of water, and their toxicity and
erosion rate after polymerization differ with the length of
their alkyl chains (
Gombotz and Pettit, 1995
). All poly-
cyanoacrylates have several limiting properties: First, the
monomers (cyanoacrylates) are very reactive compounds
that often have significant toxicity. Second, upon degra-
dation polycyanoacrylates release formaldehyde resulting
in intense inflammation in the surrounding tissue. In
spite of these inherent limitations, polycyanoacrylates
have been investigated as potential drug delivery matri-
ces and have been suggested for use in ocular drug de-
livery (
Deshpande
et al.
, 1998
).
Polyphosphazenes are very unusual polymers, whose
backbone consists of nitrogen-phosphorus bonds. These
polymers are at the interface between inorganic and
organic polymers and have unusual material properties.
Polyphosphazenes have found industrial applications,
mainly because of their high thermal stability. They have
also been used in investigations for the formulation of
controlled drug delivery systems (
Allcock, 1990
).
Polyphosphazenes are interesting biomaterials, in many
respects. They have been claimed to be biocompatible
and their chemical structure provides a readily accessi-
ble ''pendant chain'' to which various drugs, peptides, or
other biological compounds can be attached and later
released via hydolysis. Polyphosphazenes have been
examined for use in skeletal tissue regeneration
(
Laurencin
et al.
, 1993
). Another novel use of poly-
phosphazenes is in the area of vaccine design where
these materials were used as immunological adjuvants
(Andrianov
et al.,
1998).
the carrier
matrix.
On
the other hand,
the
