Biomedical Engineering Reference
In-Depth Information
authors [105, 191-196]. However, it was also reported that P3HB-3HV can be
sterilized by steam, gamma-irradiation, and ethylene oxide/carbon dioxide
without losing stress and stiffness [197].
In Vivo Degradation
The in vivo degradation (decrease of molecular weight) or resorption (mass
loss) of P3HB has long been a controversial subject in the literature. Main rea-
sons for the controversy were the use of samples made by various processing
technologies (e.g., solution-casting, melt-processing, drawing/orientation) in
different shapes and designs (e.g., films, fibers, porous scaffolds) and the in-
comparability of different implantation sites (e.g., blood contact, “soft” tissue,
“hard” tissue). However, there is now a significant body of research data avail-
able confirming that P3HB is a completely resorbable polymer, with a degra-
dation rate comparable to that of slowly degrading synthetic polyesters such
as high molecular weight PLLA. Most valuable for an estimate of the in
vivo resorption time of P3HB are studies conducted in sheep which demon-
strated the resorption of arterial implants (blood contact) after approximately
12-24 months and pericardial implants (“soft” tissue contact) after approxi-
mately 30 months (see below).
The following conflicting results reported from early studies may serve
as examples for the controversy previously existing in the literature. For
example, solution-cast and press-sintered P3HB showed beginning or com-
plete dissolution after i.m. and s.c. implantation in rabbits already within
2-8 weeks [26]. P3HB tablets lost about 7.5% of their mass within 20 weeks
s.c. in mice [28]. In contrast, no decomposition of P3HB tablets was observed
after a 6-month period s.c. in rats [198]. No significant changes of P3HB films
were reported from a 90-day s.c. implantation study in rats [199].
It has to be considered that mass loss or decomposition of P3HB occurs in
the final step of its degradation, as already outlined above. Therefore, in com-
parison to mass loss, molecular weight analysis gives a better insight into the
degradation profile of a bulk-degrading polymer such as P3HB and allows for
a more reliable prediction of its resorption time.
For example, various P3HB samples implanted for 1 year s.c. in rats
showed a decrease in the molecular weight to about 70-85% of the initial
value [192]. Systematic degradation studies of polyesters, among them P3HB,
were carried out s.c. in mice [55]. The 2%masslossofP3HBafter6monthsof
implantation was ascribed to low molecular weight impurities. The molecular
weight was reduced to 57% of the initial value. The in vivo degradation rate
had the order PDLLA > PLLA > P3HB (Fig. 10a). It was concluded that P3HB
degrades in vivo, although at a much slower rate than the poly(lactide)s.
Additionally, the in vivo degradation of P3HB was systematically com-
pared with that of P3HB-3HV in this study (Fig. 10b). P3HB-3HV copolymers
show a slower degradation than P3HB if the 3HV content is less than 10%.
However, the hydrolysis rates become comparable when the 3HV content
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