Biomedical Engineering Reference
In-Depth Information
both in the amorphous and crystalline regions of the polymer matrix associ-
ated with a decrease in the molecular weight with unimodal distribution and
relatively narrow polydispersity. Simultaneously, an increase in crystallinity
occurs that is attributed to the crystallization of chain fragments in the hy-
drolyzed amorphous regions. When the molecular weight of the degrading
polymer reaches a critical low
M
n
of about 13 000,masslossstartsasthe
second step [167].
This in vitro degradation profile is typical for a bulk-degrading polymer
and can also be found in synthetic polyesters in medical use, such as PGA,
PLGA, PDLLA, and PLLA. Thus, significant mass loss of P3HB will be ob-
served only after the prolonged period of time necessary for the molecular
weight to reach the critical lower limit. Therefore, the degradation profile can
hardly be predicted solely by determination of mass loss but should prefer-
ably be based on the molecular weight analysis.
Unmodified P3HB is a relatively slowly degrading polymer. However, an
acceleration of the degradation rate is possible by simple modifications, such
as the addition of polymers or plasticizers. One strategy is the addition of hy-
drophilic or amorphous polymers, which enhance the water absorption into
the polymer bulk and accelerate its hydrolysis. For example, the water con-
tent was found to be higher in P3HB/PDLLA than in P3HB/PCL blends [168].
Amorphous at-P3HB degrades faster than natural isotactic P3HB and can also
be used as blend component [169]. Another strategy is the leaching of water-
soluble additives, which leads to a higher polymer surface area, as discussed
for P3HB and glycerin derivatives [170]. The addition of PDLLA oligomer or
PEG as amorphous and leachable additives has also been shown to accelerate
the hydrolysis of, for example, P3HB-12%3HV [171].
The in vitro degradation of solution-cast films of P3HB and modifica-
tions of P3HB expected to influence the degradation time has been studied
(Fig. 9a). The molecular weight of unmodified P3HB decreased to one half
of its original value after 1 year of storage in buffer solution (pH 7.4, 37
◦
C).
An accelerated degradation could be achieved by blending with 30%at-
P3HB, while addition of low molecular weight (predegraded) dg-P3HB had
no influence due to its high crystallinity. Leaching of a water-soluble addi-
tive (TEC) led to a slight initial acceleration of the P3HB degradation. In
contrast, a deceleration of the degradation rate was observed after addition
of a hydrophobic plasticizer (BTHC) [38]. Slightly enhanced hydrolysis rates
could be achieved by increasing the amount of at-P3HB in the P3HB/at-P3HB
blends [39] (Fig. 9b).
An accelerating effect of pancreatin containing a mixture of enzymes
(including lipase, amylase,
-chymotrypsin, trypsin and protease) on the
hydrolysis of P3HB, but not PLLA, has been observed in this study. The degra-
dation rate of P3HB was accelerated about threefold in comparison to simple
hydrolysis [38]. There are only a few other reports on this topic in the lit-
erature. For example, microparticles made of a PHB-10.8%HV/PCL (80
α
/
20)
