**5. Degradation mechanism**

Takahara et al. (Takahara et al., 1992) degraded SPU´s based on MDI, BD and various poly‐ ols using 0.25 % phophatidyl choline and 0.1% M cholesterol liposome solution during 28 days at 37°C. They found that SPU based on PDMS disintegrated under these conditions while PTMO based SPUs exhibited a severe reduction in tensile strength and elongation. These results were not related to the presence of a specific chemical group in the soft seg‐

Synthetic poly(ester urethanes) are known to be degraded by microbes mainly due to the presence of ester linkages, being more susceptible those containing long chains rather than short polyester chains. Lactic acid based polyester urethanes have been degraded with com‐ post inoculum (thermophilic-stage household waste compost was added to 100 ml of ASTM solution and the CO2 evolved was followed by Hiltunen et al. (Hiltunen et al., 1997). The data showed that poly(ester-urethanes) did not biodegrade at 25˚C but when the tempera‐ ture was raised, biodegradation was accelerated. At 37°C the stereo structure of polymer chains had a strong effect on biodegradation. This temperature was below the glass transi‐ tion temperature of poly(ester-urethanes) but about the same as the glass transition temper‐ ature of prepolymer chains. The lower the glass transition temperature of prepolymer, the faster the biodegradation. Urethane bonds probably break first, and after that the properties of lactic acid prepolymer chains determine the biodegradation behavior. All poly(ester-ure‐ thane) samples biodegraded well at 55°C, and the percentage of biodegradation varied be‐ tween 45 and 77% in 55 days. At 60°C the poly(ester-urethanes) biodegraded well and they reached even higher levels of biodegradation than Biopac™ and lactic acid. The biodegrada‐

Polyurethanes based on MDI and PCL with different molecular weights were prepared by Watanabe et al. (Watanabe et al., 2009) and degraded by soil burial test at 28˚C. It was found that biodegradation rate of the polyurethanes increased as the number of average molecular weight (Mn) of poly(caprolactone) diol used increased from 500 to 1000 (urethane content 11.9 to 7.6 wt % respectively), whereas it decreased as the Mn of poly(caprolactone) diol in‐ creased from 1200 to 2000 (4.2 wt % of urethane content). Furthermore, when 2000 PCL triol

Although the thermal degradation of both polyurethanes (PU) and segmented polyur‐ ethanes (SPU) has been extensively investigated due to their wide range of applica‐ tions, studies on thermal decomposition of polyurethanes used specifically in biomedical field such as catheters, heart valves, vascular prostheses, etc., are less com‐ mon as generally these materials are not subjected to high temperatures during their *in vivo* performance [Cervantes-Uc et al. 2009]. In some cases, these studies are used to in‐ vestigate the composition and stability of the remaining material after the chemical hy‐ drolysis and oxidation of SPU [Chan-Chan et al. 2010] as well as to determine the soft

ment as PEO based SPU´s were not affected.

70 Advances in Biomaterials Science and Biomedical Applications

**4.6. Compost biodegradation**

tion varied from 45 to 77% in 55 days.

was used led to a high degradation ratio.

**4.7. Thermal degradation of polyurethanes**

and hard segment ratio of polyurethanes.

The nature of PU chemistry is central to understand why some PUs undergo faster degrada‐ tion than others (Santerre et al., 2005). However, the degradation mechanism of polyur‐ ethanes depends on not only the PU chemistry structure but also the degradation environment, i.e. in the presence of water, acidic, alkaline or oxidative conditions, or in the presence of enzymes. Generally, the characterization of the by-products during the degrada‐ tion of the polyurethane is the key to understand the mechanisms of degradation. Identifica‐ tion of degradation products is an important issue but of equal interest is the eventual toxicity of the degradation products. If the biomaterial degrades, either spontaneously or due to biological activity, components can leach into surrounding tissues and cause an in‐ flammatory response if not easily metabolized by natural pathways. Therefore, it is compul‐ sory to identify the major species produced at different stages of degradation and the kinetics of their formation (Azevedo et al., 2005).

Accelerated degradation has been used to determinate stability of non degradable polyur‐ ethanes (Gunatillake, 1992) but it can be used to provide valuable information about degra‐ dation mechanism of resorbable polyurethanes. In this context, both soluble products and solid residues can be studied with different analytical techniques and tests to determine their composition.

The main techniques used to evaluate the degradation of biomaterials can be divided into surface analysis (infrared spectroscopy, X-ray photoelectron spectroscopy, contact angle measurements), which are more appropriated to monitor the changes occurring in the first stages of degradation, and bulk analysis (determination of changes in molecular weight, weight loss, temperature transitions, mechanical properties) for characterizing the later stage of degradation (Azevedo et al., 2005).

In general, polyesterurethanes are susceptible to hydrolytic degradation because of ester groups in the soft segments while polyetherurethanes are susceptible to oxidative degrada‐ tion. Furthermore, it has been observed that ester linkages hydrolyze about a magnitude faster than urethane linkages, and it has been shown that urea linkages hydrolyze faster than urethane, although at slightly acidic conditions. Figure 5 shows the possible mecha‐ nism of hydrolytic degradation of various functional groups present in polyurethanes.

**Figure 5.** Hydrolytic degradation mechanism of polyesters (A), poly(urethane) (B) and poly(ureas) (C).

In spite of this, the degradation rate of the poly(ester urethane) based on PCL was found to be slow (i.e., 15% weight loss in 11 weeks (Wang et al., 2008). Furthermore, IR spectra for the degradation products of the LDI/PCL and LDI (lysine methyl ester diisocyanate)/P6C3G1L (triol synthesized from a glycerol starter and a mixture of monomers comprising 60% capro‐ lactone, 30% glycolide, and 10% DL-lactide) materials after 2 and 8 months in PBS (Guelcher et al., 2008) shows an absorption band at approximately 1070-1050 cm-1, which is assigned to C-O stretching vibrations in alcohols and carboxylic acids. This observation implies that the polyurethanes degrade by hydrolysis of ester linkages to yield α-hydroxy acids and is fur‐ ther supported by the appearance of the strong peaks at 1675-1650 cm-1, which correspond to the COO asymmetric stretching vibration associated with carboxylic acid salts. Therefore, it is possible under these conditions that phosphate salts of carboxylic acids will form in the PBS solution due to the reaction of carboxylic acids with the basic phosphate salts present in PBS. Hydrolysis of LDI/PCL containing poyurethanes networks in sodium hydroxide solu‐ tions has been reported to yield L-lysine as a degradation product; however, the presence of L-lysine in the degradation products under physiological conditions was not confirmed. Other studies reported the presence of lysine in the degradation products from lysine-de‐ rived polyurethanes networks.

stages of degradation, and bulk analysis (determination of changes in molecular weight, weight loss, temperature transitions, mechanical properties) for characterizing the later

In general, polyesterurethanes are susceptible to hydrolytic degradation because of ester groups in the soft segments while polyetherurethanes are susceptible to oxidative degrada‐ tion. Furthermore, it has been observed that ester linkages hydrolyze about a magnitude faster than urethane linkages, and it has been shown that urea linkages hydrolyze faster than urethane, although at slightly acidic conditions. Figure 5 shows the possible mecha‐ nism of hydrolytic degradation of various functional groups present in polyurethanes.

**Figure 5.** Hydrolytic degradation mechanism of polyesters (A), poly(urethane) (B) and poly(ureas) (C).

In spite of this, the degradation rate of the poly(ester urethane) based on PCL was found to be slow (i.e., 15% weight loss in 11 weeks (Wang et al., 2008). Furthermore, IR spectra for the degradation products of the LDI/PCL and LDI (lysine methyl ester diisocyanate)/P6C3G1L (triol synthesized from a glycerol starter and a mixture of monomers comprising 60% capro‐ lactone, 30% glycolide, and 10% DL-lactide) materials after 2 and 8 months in PBS (Guelcher et al., 2008) shows an absorption band at approximately 1070-1050 cm-1, which is assigned to C-O stretching vibrations in alcohols and carboxylic acids. This observation implies that the polyurethanes degrade by hydrolysis of ester linkages to yield α-hydroxy acids and is fur‐ ther supported by the appearance of the strong peaks at 1675-1650 cm-1, which correspond to the COO asymmetric stretching vibration associated with carboxylic acid salts. Therefore, it is possible under these conditions that phosphate salts of carboxylic acids will form in the PBS solution due to the reaction of carboxylic acids with the basic phosphate salts present in PBS. Hydrolysis of LDI/PCL containing poyurethanes networks in sodium hydroxide solu‐ tions has been reported to yield L-lysine as a degradation product; however, the presence of L-lysine in the degradation products under physiological conditions was not confirmed.

stage of degradation (Azevedo et al., 2005).

72 Advances in Biomaterials Science and Biomedical Applications

Segmented polyurethane based on poly(ε-caprolactone), ethyl lysine diisocyanate or hexam‐ ethylene diisocyanate in combination with ethylene glycol or ester from ethylene glycol and lactic acid (2-hydroxyethyl 2-hydroxypropanoate) with greater hard segment content (HS) liberate higher amine concentrations during their degradation (Tatai et al., 2007). Amine concentration was determined using a spectrophotometer by acquiring the A570 (absorbance at 570 nm) of the test sample and by quantifying the detected concentration with use of the standard curve. This being expected, on the assumptions that PUs with higher HS contained more urethane bonds. To detect amine groups using this technique, a degradation product must undergo hydrolysis at its respective urethane linkage. Since this process is somewhat slower than that of ester bond hydrolysis, it seems that part of the degradation product may still contain urethane segments.

Hafeman et al. (Hafeman et al., 2011) investigate the effects of esterolytic and oxidative con‐ ditions on scaffold degradation by incubating in 1 U/mL cholesterol esterase (CE), 1 U/mL carboxyl esterase (CXE), and 10 U/mL lipase (L) hydrogen peroxide (20 wt% hydrogen per‐ oxide (H2O2) in 0.1 M cobalt chloride (CoCl2), and buffer alone (0.5 M monobasic sodium phosphate buffer with 0.2% w/w sodium azide) and analysed the degradation products by HPCL. Hydrolysis of ester bonds was anticipated to yield α-hydroxy acids (e.g., hydroxy‐ caproic, lactic, and glycolic acids), which was confirmed by HPLC. The lysine triisocyanate (LTI) scaffolds produced more α-hydroxy acids than trimer of hexamethylene diisocyanate (HDIt) scaffolds. The 7C/LTI (triol synthesized from a glycerol starter and a mixture of mon‐ omers comprising 70% caprolactone, 30% glycolide and 10% lactide) formulation, which de‐ graded more slowly due to the longer polyester half-life, yielded lower concentrations of αhydroxy acids than the 6C/LTI (60% caprolactone, 30% glycolide and 10% lactide) formulation. Inclusion of polyethylene glycol (PEG) in the 6C/HDIt scaffold reduced the amount of α-hydroxy acids in the degradation medium due to the replacement of 50% of the polyester with PEG. Several unidentified peaks appeared in the HPLC spectra, which are conjectured to be adducts of α-hydroxy acids and either lysine or ethanolamine connected by urethane or urea bonds. Oxidation of urethane and urea bonds was predicted to yield ly‐ sine and ethanolamine from LTI scaffolds, and cyanuric acid from HDIt scaffolds. Both ly‐ sine and ethanolamine were detected in the degradation products from LTI scaffolds when incubated in PBS; however, cyanuric acid was not detected in the degradation products from HDIt scaffolds. The amount of lysine recovered from 6C/LTI scaffolds was significant‐ ly greater than that from 7C/LTI scaffolds after 14 weeks, which is consistent with the faster *in vitro* degradation of the 6C/LTI materials. At 36 weeks, 18% of the lysine incorporated in the 6C/LTI scaffolds was recovered, while 100% of the original mass had degraded to solu‐ ble degradation products. This suggests that the majority of the lysine was incorporated in soluble urethane and urea adducts with α-hydroxy adducts. The recovery of ethanolamine arises from the hydrolysis of the ester group in LTI and a urethane bond. Ethanolamine was not detected (<0.001 μg/mg polyurethane) until 14 weeks, and at later time points the etha‐ nolamine concentration increased with time. The recovery of ethanolamine upon complete dissolution of the 6C/LTI scaffold at 36 weeks was 9%.

Suntherland et al. (Sutherland et al., 1993) degraded Pellethane 2363 80A with either HClO or ONOO. An oxidative reaction involving the ether or ester moieties of PEU would be re‐ flected by a decrement in the urethane-aliphatic ester and/or aliphatic ether stretching peaks on ATR/FTIR analysis. Indeed, a substantial decrement in the aliphatic ether stretching at 1105-1110 cm-1 relative to the urethane-aliphatic ester peak at 1075 cm-1 has been observed in implanted material. In fact, the intensity of both aliphatic ether and urethane-aliphatic ester peaks decreases after long-term implantation, suggesting that both groups are oxidized *in vivo*. PEU previously exposed to HClO exhibited a decrement in the signal from the ure‐ thane-aliphatic ester.

FTIR has been used to determine the composition of residues after degradation. In this sense, hydrolytic degradation of polyester urethanes affects carbonyl bands at 1730 cm-1. Soluble products of the ester scission are carboxyl acids and alcohols that can be observed between 2500 and 3500 cm-1. Pérez et al. (Pérez et al., 2006) studies showed that urea bonds derived from amino acids can be hydrolyzed in basic conditions but after more prolonged period than ester groups, this degradation was monitored by capillary electrophoresis-ion trap-mass.

Oxidative degradation has been generally associated with poly(ether-urethane)s, since many studies have determined that these polymers degrade by mean alpha-hydrogen abstraction adjacent to oxygen in polyethers and polycarbonates (Christenson et al., 2004; Xie et al., 2009). In contrast, few works related to oxidative degradations on polyester polyurethanes has been done, and even less has studied the mechanism of degradation of polyurethane ureas. However recent studies about oxidative degradations of PCL and polyester poly(ure‐ thane urea)s PCL based have showed ester, urethane and urea groups are susceptible to oxi‐ dative degradation (Sabino, 2007; Sarkar et al., 2007; Hafeman et al., 2011). This mechanism is illustrated in Figure 6.

**Figure 6.** Mechanism of oxidative degradation by H2O2 in poly(ether urethanes) (A), poly(carbonate urethanes) (B) and aromatic polyurethanes (C).

Oxidative degradation using HClO is less commonly pursued but it may be clinically more relevant as hipochlorous anions can be produced by neutrophils. These conditions can be si‐ mulated *in vitro* and the suggested mechanisms of the polyurethane degradation can be de‐ picted in Figure 7.

$$\begin{array}{ccccccccc} \text{O} & \text{H} & & \text{H} & & \text{ClO}^{-} & & \text{O} & & \text{H} & & \\ \text{R}-\text{C}-\text{O}-\text{C}-\text{R} & & \text{ClO}^{-} & & & \text{O} & & \text{H} & & \\ & \underset{\text{H}}{\overset{\text{l}}{\rightleftharpoons}} & & & \text{R}-\text{C}-\text{O}^{-} & + & \text{O}=\text{C}-\text{R} & + & \text{H}^{+} & + & \text{Cl}^{-} \\ & & & & & & & & \text{O} & \\ \end{array}$$

**Figure 7.** Mechanism of oxidative degradation in polyurethanes by means of HClO

nolamine concentration increased with time. The recovery of ethanolamine upon complete

Suntherland et al. (Sutherland et al., 1993) degraded Pellethane 2363 80A with either HClO or ONOO. An oxidative reaction involving the ether or ester moieties of PEU would be re‐ flected by a decrement in the urethane-aliphatic ester and/or aliphatic ether stretching peaks on ATR/FTIR analysis. Indeed, a substantial decrement in the aliphatic ether stretching at 1105-1110 cm-1 relative to the urethane-aliphatic ester peak at 1075 cm-1 has been observed in implanted material. In fact, the intensity of both aliphatic ether and urethane-aliphatic ester peaks decreases after long-term implantation, suggesting that both groups are oxidized *in vivo*. PEU previously exposed to HClO exhibited a decrement in the signal from the ure‐

FTIR has been used to determine the composition of residues after degradation. In this sense, hydrolytic degradation of polyester urethanes affects carbonyl bands at 1730 cm-1. Soluble products of the ester scission are carboxyl acids and alcohols that can be observed between 2500 and 3500 cm-1. Pérez et al. (Pérez et al., 2006) studies showed that urea bonds derived from amino acids can be hydrolyzed in basic conditions but after more prolonged period than ester groups, this degradation was monitored by capillary electrophoresis-ion

Oxidative degradation has been generally associated with poly(ether-urethane)s, since many studies have determined that these polymers degrade by mean alpha-hydrogen abstraction adjacent to oxygen in polyethers and polycarbonates (Christenson et al., 2004; Xie et al., 2009). In contrast, few works related to oxidative degradations on polyester polyurethanes has been done, and even less has studied the mechanism of degradation of polyurethane ureas. However recent studies about oxidative degradations of PCL and polyester poly(ure‐ thane urea)s PCL based have showed ester, urethane and urea groups are susceptible to oxi‐ dative degradation (Sabino, 2007; Sarkar et al., 2007; Hafeman et al., 2011). This mechanism

**Figure 6.** Mechanism of oxidative degradation by H2O2 in poly(ether urethanes) (A), poly(carbonate urethanes) (B)

Oxidative degradation using HClO is less commonly pursued but it may be clinically more relevant as hipochlorous anions can be produced by neutrophils. These conditions can be si‐ mulated *in vitro* and the suggested mechanisms of the polyurethane degradation can be de‐

dissolution of the 6C/LTI scaffold at 36 weeks was 9%.

74 Advances in Biomaterials Science and Biomedical Applications

thane-aliphatic ester.

is illustrated in Figure 6.

and aromatic polyurethanes (C).

picted in Figure 7.

trap-mass.

Degradation of polyurethanes with H2O2 (30% v/v) does not seem to affect ester bonds but affect urea bonds as observed by FTIR. The wide band of 3650-3400 cm-1 and a small peak in 930 cm-1 corresponding to carboxylic acid confirm scission of urea groups as shown in Fig‐ ure 8. Other bands such as those at 1298 cm-1 show some crosslinking by C-N bonds and an increase in PCL crystallinity, as the 1143 y 1189 cm-1 bands, corresponding to amorphous and crystalline PCL, changed (Chan-Chan, 2012).

**Figure 8.** FTIR spectra of poly(urethane ureas) degraded in various media.

### **6. Conclusions**

Polyurethanes are very versatile polymers that found application in the biomedical field, es‐ pecially in cardiovascular applications. In spite of their good physicochemical and mechani‐ cal properties and acceptable biocompatibility they are prone to degradation under different conditions. These conditions range from hydrolysis, oxidation, metal induced oxidation, en‐ vironmental stress cracking, enzyme-assisted degradation, etc. which can be found *in vivo* during the useful life of the device. In order to simulate these, *in vitro* approaches has been followed. Thanks to this information today it is well accepted that polyurethanes are no lon‐ ger inert materials placed within the body. However, this disadvantage can be used to mod‐ ulate their degradation to a rate that can be controlled mainly by their composition, and be used in the design of tissue engineering scaffolds.
