Biomedical Engineering Reference
In-Depth Information
Based on the
1
H NMR study, Puiggali
et al.
[10] also concluded that the hydrolytic
degradation of PEA composed of sebacic acid, l - alanine, and 1,2 - dodecanediol
(PEA
8A12
obtained by IP) takes place in the ester bonds and amide groups remain
unchanged.
Nagata [13] also studied the enzymatic degradation of PEAs stereopolymers
derived from l - and d - alanine, using proteolytic enzymes (proteinase - K, papain,
and
-chymotrypsin), and lipase, and also confi rmed that the degradation of PEAs
with this group of hydrolases proceeds via the hydrolysis of the ester linkages
and amide groups remain unchanged. The
in vitro
biodegradation mechanism
of PEAs predominately via ester bonds hydrolysis was also suggested by Saotome
et al.
[6] .
It has to be noted that the biodegradation rate as well as mechanical and
physical-chemical properties of AABBPs can be manipulated in the widest range
not only by changing their stereochemical composition (i.e., using l - and d -
isomers of one
α
α
- AA [10, 13]) but also by preparing copolymers with two or more
α
-AAs [7, 19, 66], two or more dicarboxylic acids [19, 28]. An alternative way to
tailor the properties of AABBPs lies in blending the polymers [18]. The blending
of AABBPs of various classes looks possible as well because high affi nity of mac-
romolecules can guarantee their compatibility.
A preliminary
in vivo
biodegradation study of selected PEA (
4F4
) fi lms in rats,
with and without impregnated lipase [66], showed that PEAs impregnated with
lipase were completely absorbed within 1-2 months, or within 3-6 months for the
lipase-free samples. These fi ndings prompt to suggest that new PEAs may have a
great potential for designing drug-sustained/controlled release devices as well as
implantable surgical devices.
5.2.4.3
Biocompatibility of AABBP s
Among AABBPs, only few PEAs were studied for biocompatibility. For example,
the PEA composed of adipic acid, l - phenylalanine, and 1,4 - butanediol (PEA
4F4
)
supported the growth of human osteosarcoma and fi broblasts cells and showed
the material to be biocompatible (Y. Shved and R. Katsarava, unpublished results) .
Aqueous solutions of model biodegradation products -
N
,
N
- adipoyl - bis - l -
phenylalanine and 1,4 - butanediol - at 1:1 mol ratio were subcutaneously injected
to rats. No acute or chronic toxicity was observed [68]. LD
50
could not be deter-
mined since it was higher than 1500-fold excess (6 g/kg) of an average therapeutic
dose, confi rming high biocompatibility of the PEA and its biodegradation
products.
Elastomeric functional
co -
PEA on the basis of sebacic acid (1.00 mol), TAAD
composed of l-leucine and 1,6-hexanediol (0.75 mol), and l - lysine (0.25 mol) [
co -
PEA
8(L6)
0.75
K
0.25
] [15, 16] showed excellent blood and tissue compatibility in both
in vitro
[69] and
in vivo
(pigs) [70] tests. The same
co -
PEA selectively supported the
in vitro
growth of epithelial cells [69]. The
in vivo
biocompatibility was tested in
porcine coronary arteries, comparing the polymer-coated stents with bare metal
stents in 10 pigs [70]. All animals survived till sacrifi ced 28 days later. Prior to
sacrifi ce, angiography revealed identical diameter stenosis in both groups. Histol-
ogy confi rmed similar injury scores, infl ammatory reaction, and area stenosis.
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