Biomedical Engineering Reference
In-Depth Information
increasing the kinetics of the degradation process. The degradation process can be modulated by
modifi cation of the backbone of the polymer chain, and thus it provides the possibility of tailoring to
regulate bulk degradation rates. Recently, it was hypothesized that surface erosion could be modi-
fi ed by tuning the hydrophobicity of a polymer backbone using a modular approach to polymer syn-
thesis, wherein judiciously designed building blocks of varying lipophilicities are linked together
using hydrophobic spacers. Based on this rationale, Xu et al. reported the synthesis of a library of
polymers by designing macromonomer diols with differing lipophilicities, and then chemically
reacting them with diacid spacers with thermal and physical properties distinct from pure PLLA
and enhanced surface erosion behavior.
12
The processing of PLA, PGA or copolymers, and subsequent sterilization techniques, has
an impact on the molecular weight, crystallinity, and morphology of the resorbable implants.
A systematic
in vivo
study by Chawla and Chang, with four different molecular weight PLA
polymers implanted in rats, showed conclusively that the lower molecular weight polymers had a
faster rate of degradation. This observation is associated with the difference in morphology and
crystallinity.
13
Although, extrapolating
in vitro
degradation studies to
in vivo
models is not always
linear,
in vitro
degradation studies confi rm that degradation rates vary and thus the tailoring of
copolymers to best justify a particular application is possible. The degradation of the suture Dexon
based on PGA was reported to occur as a result of bulk degradation with selective attack on the
amorphous regions.
14
Chu suggested that the diffusion of the oligomers was a signifi cant compo-
nent in the later stages of hydrolysis. The examination of the microstructure by scanning electron
microscopy also supported the theory of the preferential attack and hydrolysis of the amorphous
domains.
15
It was also reported that annealed specimens exhibited a faster rate of loss of mechani-
cal properties than unannealed specimens when subjected to hydrolysis.
16,17
It is also important
to note that a faster rate of the decrease in mechanical properties does not necessarily imply that
it will exhibit a faster rate of degradation. Additionally, the degradation medium also infl uences
the
in vitro
degradation rates. The degradation in both physiological and acidic media for Dexon
and Vicryl were reported to not have a profound effect on the degradation, however, for the latter,
maximum retention of tensile strength was obtained at a pH of 7.
18
In contrast, an alkaline buffer
medium had a remarkable effect on the degradation and weight loss was reported to occur with
increasing pH values.
19,20
Surface chemistry and topography are important parameters for both biocompatibility and per-
formance of biomedical devices. Any surface modifi cations that enhance cell adhesion, cell growth,
and proliferation are advantageous for biomedical applications. Surface wettability is another
important parameter since it has been established that moderately hydrophilic surfaces favor cel-
lular adhesion and biocompatibility. Thus, covalent surface modifi cation is generally favored over
physical adsorption because of superior environmental stability. The molecular weight of PLLA
and other aliphatic polyesters deteriorate through processing and sterilization, naturally infl uencing
the overall degradation profi le of the fi nal processed polymer. Polymers generally tend to degrade
as a result of processing and parameters such as temperature, residence time, presence of moisture,
shearing action, and irradiation.
21
The biocompatibility of PGA and PLA have been reviewed by Böstman and Pihlajamäki.
22
In vitro
biocompatibility evaluation of these polymers is limited, however a large number of investi-
gations report
in vivo
studies of particular devices.
23,24
The
in vitro
acute toxicity of two copolymers,
namely, 70:30 poly (l,d, d,l-lactide) (PLDLA), and 90:10 poly(l-lactide-
co
- glycolide) (PLGA), were
evaluated by the agar diffusion test and the fi lter test with L929 mouse fi broblasts.
25
The leachables
from these copolymers obtained at temperatures of 37
C, were assessed for mitochondrial
succinate dehydrogenase activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT assay) and the incorporation of 5-bromo-2
°
C and 70
°
-deoxyuridine (BrdU) into DNA of BALB 3T3
cells. Both materials revealed no signs of cytotoxicity during the agar diffusions and the MTT and
BrdU assays PLDLA and PLGA showed similar results. The temperature at which the leachables
were extracted was observed to exhibit an infl uence on the mitochondrial activity, with cells treated
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