Biomedical Engineering Reference
In-Depth Information
(Barrows, 1986). The polymer had good mechanical properties and acceptable tissue biocompatibility.
Unfortunately, there is currently no commercial use of this class of polymer in surgery.
5.4.2 Poly(alkylene oxalates) and Copolymers
This class of high-crystalline biodegradable polymers was initially developed (Shalaby, 1994) for absorb-
able sutures and their coating. They consist of [-ROOC-COO-]
n
repeating unit where R is (CH
2
)
x
with
x
ranging from 4 to 12. R could also be cyclic (1,4-
trans
-cyclohexanedimethanol) or aromatic (1,4-benzene,
1,3-benzene dimethanol) for achieving higher melting temperature. The biodegradation properties
depend on the number of (CH
2
) group,
x
, and the type of R group (i.e., acyclic versus cyclic or aromatic).
In general, a higher number of methylene group and/or the incorporation of cyclic or aromatic R group
would retard the biodegradation rate and hence make the polymer absorbed slower. For example, there
was no mass of the polymer with
x
= 4 remaining
in vivo
(rats) after 28 days, while the polymer with
x
= 6
retained 80% of its mass after 42 days
in vivo
. An isomorphic copolyoxalate consisting of 80% cyclic R
group like 1,4-
trans
-cyclohexanedimethanol and 20% with acyclic R group like 1,6-hexanediol retained
56% of its original mass after 180 days
in vivo
. By varying the ratio of cyclic to acyclic monomers, copo-
lymers with a wide range of melting temperatures could be made, for example, copolymer of 95/5 ratio of
cyclic (i.e., 1,4-
trans
-cyclohexanedimethanol)/acyclic (i.e., 1,6-hexanediol) monomers had a
T
m
= 210°C,
while the copolymer with 5/95 ratio had a
T
m
= 69°C. Poly(alkylene oxalates) with
x
= 3 or 6 had been
experimented with drug control/release devices. The tissue reaction to this class of biodegradable poly-
mers has been minimal.
5.4.3 Amino Acid-Based Poly(ester amide)s and Copolymers
The rationale for designing poly(ester amide)s (PEAs) is to combine the predictable hydrolytic-induced
degradability and biocompatibility of linear aliphatic polyesters with the high-performance and enzy-
matically catalyzed biodegradability of polyamides and the potential chemical reactive sites of amide in
polyamides into one single entity. Instead of using the block copolymer approach to provide both ester
and amide linkages in a polymer backbone, PEAs have both ester and amide linkages within the same
repeating unit and different versions of PEAs have been reported.
Two basic types of PEAs exist: nonamino-acid-based PEAs synthesized from polyesterification of
amidediol monomers (which contain preformed amide linkages from aliphatic diamines) (Barrows,
1994; Paredes et al. 1998) and amino-acid-based PEAs (AA-PEAs) synthesized from solution polycon-
densation of amino acids, diols, and dicarboxylic acids (Katsarava et al., 1985, 1999; Chu and Katsarava,
2003; Guo et al., 2005; Guo and Chu, 2007a,b, 2008, 2010; Jokhadze et al., 2007; De Wit et al., 2008;
Deng et al., 2009, 2011; Pang et al., 2010; Pang and Chu, 2010a,b; Chkhaidze et al., 2011). PEAs obtained
from amidediols (i.e., nonamino-acid based) cannot be considered bioassimilative polymers because
the water-soluble amidediols (first product of biodegradation) were extensively excreted without change
(i.e., without the liberation of toxic diamine) in the urine.
Katsarava and Chu et al. reported the synthesis of high-molecular-weight amino acid-based poly(ester-
amides) (AA-PEAs) of
M
w
from 24,000 to 167,000 with narrow polydispersity (
M
w
/
M
n
= 1.20−1.81) via
solution polycondensation of di-
p
-toluenesulfonic acid salts of bis-(α-amino acid) α,ω-alkylene dies-
ters and di-
p
-nitrophenyl esters of diacids (Katsarava et al., 1999). These AA-PEAs consist of naturally
occurring and nontoxic building blocks and had excellent film and fiber-forming properties. These
AA-PEA polymers were mostly amorphous materials with
T
g
from −7.3 to 109°C. The rationale for
making AA-PEAs is to combine the well-known absorbability and biocompatibility of linear aliphatic
polyesters with the high performance and the flexibility of potential chemical reactive sites of amide
of polyamides. AA-PEAs could be biodegraded either by enzyme and/or nonenzymatic mechanisms.
There have been several trials of this new class of AA-PEA copolymers as the coating for drug-eluting
stents as well as synthetic vaccines at present.
