Biomedical Engineering Reference
In-Depth Information
new approach could provide scientists with a better understanding of the relationship between the
chemical structure of biodegradable polymers and their degradation behavior at a molecular level. It
also could help the future research and development of this class of polymers through the intelligent
prediction of structure-property relationships. In those studies, Pratt and Chu examined the affect of
various derivatives of linear aliphatic polyester (PGA) and a naturally occurring linear polysaccharide
(hyaluronic acid) on their hydrolytic degradation phenomena and mechanisms.
The data showed a decrease in the rate of hydrolysis by about a factor of 106 with isopropyl ct-substit-
uents, but nearly a sixfold increase with t-butyl --substituents (Pratt and Chu, 1993). The role of elec-
tron-donating and electron-withdrawing groups on the rate of hydrolytic degradation of linear aliphatic
polyesters was also theoretically modeled by Pratt and Chu (Pratt and Chu, 1994a). Electron-withdrawing
substituents to the carbonyl group would be expected to stabilize the tetrahedral intermediate resulting
from hydroxide attack, that is, favoring hydroxide attack but disfavoring alkoxide elimination. Electron-
releasing groups would be expected to show the opposite effect. Similarly, electronegative substituents on
the alkyl portion of the ester would stabilize the forming alkoxide ion and favor the elimination step. Pratt
and Chu found that the rate of ester hydrolysis is greatly affected by halogen substituents due primarily
to charge delocalization. The data suggest that the magnitude of the inductive effect on the hydrolysis of
glycolic esters decreases significantly as the location of the substituent is moved further away from the
--carbon because the inductive effect is very distance-sensitive. In all three locations of substitutions (-
and γ), Cl and Br substituents exhibited the largest inductive effect compared to other halogen elements.
Therefore, Pratt and Chu concluded that the rate of ester hydrolysis is greatly affected by both alkyl
and halogen substituents due primarily to either steric hindrance or charge delocalization. In the steric
effect, alkyl substituents on the glycolic esters cause an increase in activation enthalpies and a cor-
responding decrease in reaction rate, up to about three carbon sizes, while bulkier alkyl substituents
other than isopropyl make the rate-determining elimination step more facile. It appears that aliphatic
polyesters containing isopropyl groups, or slightly larger linear alkyl groups, such as
n
-butyl,
n
-pentyl,
and so on, would be expected to show a longer strength retention, given the same fiber morphology. In
the inductive effect, ct-substituents on the acyl portion of the ester favor the formation of the tetrahedral
intermediate through charge delocalization, with the largest effect seen with Cl substitution, but retard
the rate-determining alkoxide elimination step by stabilizing the tetrahedral intermediate. The largest
degree of stabilization is caused by the very electronegative F substituent.
5.5.2 The Role of Free Radicals in Degradation Properties
Salthouse et al. had demonstrated that the biodegradation of synthetic absorbable sutures is closely
related to macrophage activity through the close adhesion of macrophage onto the surface of the absorb-
able sutures (Matlaga and Salthouse, 1980). It is also known that inflammatory cells, particularly leuko-
cytes and macrophages, are able to produce highly reactive oxygen species such as superoxide (
•
O
2−
) and
hydrogen peroxide during inflammatory reactions toward foreign materials (Badwey and Kamovsky,
1980; Devereux et al., 1991). These highly reactive oxygen species participate in the biochemical reac-
tion, frequently referred to as a respiratory burst, which is characterized by the one electron reduction
of O
2
into superoxide via either NADPH or NADH oxidase as shown below. The reduction of O
2
results
in an increase in O
2
uptake and the consumption of glucose.
+
→
(NADPH oxidase)
+
2O
NADP
H
2O
i
−
NADP
+
+
H
+
2
2
(5.1)
The resulting superoxide radicals are then neutralized to H
2
O
2
via cytoplasmic enzyme superoxide
dismutase (SOD).
(SOD)
2O
i
2
−
+ →
2H
HO
+
O
22
2
(5.2)
