New Trends in Polymers - Progress in Organic and Physical Chemistry: Structures and Mechanisms - page 198

Some of the researchers studied a biodegradation of PHB threads with a tendency
of analysis of its mechanical properties in vivo [17, 18]. It was shown that at ¿ rst
load at break index decreased rapidly from 440 to 390 g (12%) at 15 th day and then
gradually increased to the initial value at 90 th day and remain almost unchanged up
to 182 nd day [17] or gradually decreased in 27% during 180 days [18], strain at break
decreased rapidly from 60 to 50% (in 17% of initial value) at 10 th day and then gradu-
ally increased to 70% (in 17% of initial value) at 182 nd day [17] or did not change
signi¿ cantly during 180 days [18].
It was demonstrated that the primary reason of PHB biodegradation in vivo
was a lysosomal and phagocytic activity of polynucleated macrophages and giant
cells of foreign body reaction. The activity of tissue macrophages and nonspeci¿ c
enzymes of a body liquids made a main contribution to signi¿ cantly more rapid rate
of PHB biodegradation in vivo in comparison with rate of PHB hydrolysis in vitro .
The PHB material was encapsulated by degrading macrophages. Presence of PHB
stimulated uniform macrophage in¿ ltration, which is important for not only the
degradation process but also the restoration of functional tissue. The long absorp-
tion time produced a foreign body reaction, which was restricted to macrophages
forming a peripolymer layer [18, 53, 56, 59]. Very important data that clari¿ es the
tissue response that contributes to biodegradation of PHB was obtained by Lobler
M. It was demonstrated a signi¿ cant increase of expression of two speci¿ c lipases
after 7 and 14 days of PHB contact with animal tissues. Moreover, liver speci¿ c
genes were induced with similar results. It is striking that pancreatic enzymes are
induced in the gastric wall after contact with biomaterials [40]. Saito T. et al. sug-
gested the presence of at least two types of degradative enzymes in rat tissues: liver
serine esterases with the maximum of activity in alkaline media (pH = 9.5) and kid-
ney esterases with the maximum of activity in neutral media [19]. The mechanism
of PHB biodegradation by macrophages was demonstrated at cultured macrophages
incubated with particles of low-molecular weight PHB [61]. It was shown that mac-
rophages and, to a lesser level, ¿ broblasts have the ability to take up (phagocytize)
PHB particles (1-10 —m). At high concentrations of PHB particles (>10 —g/ml)
the phagocytosis is accompanied by toxic effects and alteration of the functional
status of the macrophages but not the ¿ broblasts. This process is accompanied by
cell damage and cell death. The elevated production of nitric oxide (NO) and tu-
mor necrosis factor alfa (TNF-Į) by activated macrophages were observed. It was
suggested that the cell damage and cell death may be occur due to phagocytosis of
large amounts of PHB particles: after phagocytosis, polymer particles may ¿ ll up
the cells, it cause cell damage, and cell death. It was demonstrated also that phago-
cytized PHB particles disappeared in time due to an active PHB biodegradation
process (Figure 6) [61].