**4.** *In vitro* **degradation to simulate** *in vivo* **degradation**

*In vivo* experimentation using an animal model is not always available for elucidating the degradation mechanism of polyurethanes. Instead, various *in vitro* experiments have been designed to simulate their *in vivo* degradation. Among these tests, hydrolytic degradation has been conducted using distilled water (at elevated temperature), strong acids and alka‐ lies, and sometimes physiological conditions using Phosphate Buffer Saline (PBS) as degra‐ dating media.

#### **4.1. Hydrolytic degradation**

**3.1. Calcification**

58 Advances in Biomaterials Science and Biomedical Applications

sis (Bernacca et al., 1997).

adhesion have been investigated (Xu et al., 2010).

thrombogenicity (Yan et al., 2007).

**3.2. Thrombosis**

Mineralization or calcification (formation of various types of calcium phosphates such as apatite) is a well documented event in various medical devices, especially in those used in the cardiovascular field. Calcification is in fact, the most common macroscopic cause of failure in heart valves including those made of polyurethanes (Santerre et al., 2005). Even when calcification has been identified in heart valves, *in vitro* experiments on SPU showed little mineralization and associated exclusively to failure regions, indicating that the SPU´s have a lower intrinsic capacity for calcification compared to bovine bioprosthe‐

Plasma protein adsorption is well accepted as one of the first events to occur when blood is in contacts with a biomaterial. These adsorbed proteins mediate the subse‐ quent interactions of cells and platelets with the surface and may induce thrombus for‐ mation, which remains one of the major problems associated with the long-term use of blood-contacting medical devices. The surface properties of the implanted materials are determinant in protein adsorption and biological interactions with the material. The ef‐ fects of various physicochemical properties such as surface hydrophilicity/hydrophobici‐ ty balance, surface charge density, ability to form hydrogen bonds, and chemical composition of biomaterials on protein adsorption as well as subsequent blood platelet

Antithrombogenicity is one of the essential requirements for a vascular graft, but it is very difficult to achieve. There are two common approaches employed to attain this goal. One is to develop biomaterials with inherent antithrombogenicity or to use sur‐ face modified biomaterials with an anticoagulant. The other approach is to quickly and completely endothelialize the inner surface of the tubular scaffolds, thereby, reducing

Thrombosis is a leading cause of vascular graft failure in small-diameter prostheses, where it leads to decreased flow or occlusion. In addition to inducing acute or suba‐ cute failure of grafts, it may be a cause of late failure owing to thrombosis superim‐ posed on stenosis due to other causes of vessel narrowing, such as intimal hyperplasia. Methods to improve vascular grafts (e.g., antithrombotic therapy) have been shown to be beneficial in decreasing graft occlusion after surgery. Agents known to inhibit thrombogenesis or promote anticoagulation (e.g., heparin, prostaglandin E1, hirudin, di‐ pyridamole, tissue factor pathway inhibitor and aspirin) have also been bound to the

Traditionally, SPUs have been used as permanent devices such as pacemaker leads insula‐ tion and ventricular assisting devices. When used as pacemaker lead insulators, they substi‐ tute silicone rubbers and have been used as biostable polymer for outer or inner insulated

lumen of the synthetic vessels (Wang et al., 2007; Lu et al., 2012).

**3.3. Environmental stress cracking and metal ion oxidation**

Degradation of segmented polyurethanes through hydrolysis depends strongly not only on the chemical composition of the soft segment, when is the major component, but also on the rigid segment chemistry. It is generally accepted that water absorption is a necessary condi‐ tion for hydrolytic degradation of materials. Therefore, in a typical hydrolytic degradation test the rate of water absorption (or sample weight gain) can be correlated with sample weight loss (Mondal et al., 2012).

The presence of labile ester linkages in PCL containing polyurethanes makes them suscepti‐ ble to degradation in the presence of water (Gunatillake et al., 1992; Nakajima-Kambe et al., 1999; Kannan et al., 2006). This type of reactions is catalysed by the presence of acids or alka‐ line compounds. In some cases, the acid is produced by the degradation of the soft segment; caproic acid in the case of PCL or lactic acid in the case of PLA. Polyester urethanes are more prone to hydrolytic degradation although they are more resistant to oxidative environments as can be observed in Table 2, where PCL based polyurethanes (BSPU1 and BSPU2) and a commercial polyether polyurethane (Tecoflex) are compared (Chan-Chan et al., 2010).


\* BSPU's were prepared with PCL, HMDI and either butanediol (BSPU1) or dithioerythritol (BSPU2) as chain extenders.

**Table 2.** Polyurethane mass loss (%) after degradation under hydrolytic and oxidative accelerated conditions

Because of the susceptibility of the ester groups to hydrolysis, biodegradable poly(ester ure‐ thanes) degrade *in vitro* through bulk erosion via chain scission. During hydrolysis, new car‐ boxylic acid groups are formed that auto-catalyze the degradation, leading to faster degradation in the bulk than at the surface. Thus, a decrease in molecular weight preceding the loss of mechanical properties and weight loss is typical for such degradation. In addi‐ tion, an increase in crystallinity is observed, if the soft segment contains a crystalline frac‐ tion. Polyesters in the soft segment will, therefore, increase the effect of hydrolysis compared with polyether or polycarbonates (Ma et al., 2012).

Tanzi et al. (Tanzi et al., 1991) degraded various commercial polyurethanes used in the car‐ diovascular field among them Cardiothane 51, Pellethane 2363 80A, Estane 5714 Fl, Estane 58810 and Biomer. The degradation was conducted in water or alkaline borate buffer (pH 10) at 37˚C, 60˚C and 85˚C from 96 h to 168 h. They found that after hydrolytic degradation in distilled water at 85˚C for 96 h, borate buffer during 96 h at 60˚C and borate buffer during 168 h at 37˚C there were no changes in tensile properties although a reduction in molecular weight was reported.

Polyester urethanes based on methylene-bis(4-phenylisocyanate) (MDI), BD and polyadi‐ pate diol were prepared by Pretsch (Pretsch et al., 2009) and accelerated degradation studied in distilled water at 80˚C where the degradation process was followed by DSC. It was found that the intensities of the melting peaks and therefore the crystallinity of the soft segments increase after one day. Then, two main degradation scenarios were proposed: first, a hydro‐ lytic scission of polymer chains in the molten soft segments take place, which is accelerated by the ''high'' immersion temperature; second, and on top of it, there is an annealing effect. For example, the domains of segmented polyurethane elastomers may become unstable at high temperatures and mixing of hard and soft segments is enforced.

Wang et al. (Wang et al., 2011a) prepared segmented polyurethanes based on poly(D,L-lactic acid)diol, hexamethylene diisocyanate (HDI) and with either peperazine (SPU-P), 1,4-buta‐ nediol (SPU-O) or 1,4-butanediamine (SPU-A) as chain extenders. The degradation process was conducted in double distilled water at 37˚C and 50 rpm. For these SPUs, acidic groups from the degradation of PDLLA and BD could reduce the pH value of medium, while the dissolution of the hard segment (amide group and carbamide) could alkalize the medium; after 12 weeks, the pH values of SPU-O, SPU-A and SPU-P were 2.57, 3.87 and 3.71, respec‐ tively. These results suggest that the chain extender can play a main role in the degradation mechanism as using an alkaline chain extender can neutralize the acidity, the hydrophilicity and hydrolysis sensitivity of these bonds.

#### **4.2. Oxidative degradation**

rigid segment chemistry. It is generally accepted that water absorption is a necessary condi‐ tion for hydrolytic degradation of materials. Therefore, in a typical hydrolytic degradation test the rate of water absorption (or sample weight gain) can be correlated with sample

The presence of labile ester linkages in PCL containing polyurethanes makes them suscepti‐ ble to degradation in the presence of water (Gunatillake et al., 1992; Nakajima-Kambe et al., 1999; Kannan et al., 2006). This type of reactions is catalysed by the presence of acids or alka‐ line compounds. In some cases, the acid is produced by the degradation of the soft segment; caproic acid in the case of PCL or lactic acid in the case of PLA. Polyester urethanes are more prone to hydrolytic degradation although they are more resistant to oxidative environments as can be observed in Table 2, where PCL based polyurethanes (BSPU1 and BSPU2) and a commercial polyether polyurethane (Tecoflex) are compared (Chan-Chan et al., 2010).

BSPU1\* 1.46 ± 0.08 63.42 ± 7.63 82.70 ± 2.60 13.08 ± 3.35 BSPU2\* 6.15 ± 1.35 87.23 ± 4.76 52.65 ± 13.26 19.07 ± 7.01 Tecoflex 0.63 ± 0.3 1.66 ± 0.66 1.48 ± 1.62 2.16 ± 1.47

\* BSPU's were prepared with PCL, HMDI and either butanediol (BSPU1) or dithioerythritol (BSPU2) as chain extenders.

Because of the susceptibility of the ester groups to hydrolysis, biodegradable poly(ester ure‐ thanes) degrade *in vitro* through bulk erosion via chain scission. During hydrolysis, new car‐ boxylic acid groups are formed that auto-catalyze the degradation, leading to faster degradation in the bulk than at the surface. Thus, a decrease in molecular weight preceding the loss of mechanical properties and weight loss is typical for such degradation. In addi‐ tion, an increase in crystallinity is observed, if the soft segment contains a crystalline frac‐ tion. Polyesters in the soft segment will, therefore, increase the effect of hydrolysis

Tanzi et al. (Tanzi et al., 1991) degraded various commercial polyurethanes used in the car‐ diovascular field among them Cardiothane 51, Pellethane 2363 80A, Estane 5714 Fl, Estane 58810 and Biomer. The degradation was conducted in water or alkaline borate buffer (pH 10) at 37˚C, 60˚C and 85˚C from 96 h to 168 h. They found that after hydrolytic degradation in distilled water at 85˚C for 96 h, borate buffer during 96 h at 60˚C and borate buffer during 168 h at 37˚C there were no changes in tensile properties although a reduction in molecular

Polyester urethanes based on methylene-bis(4-phenylisocyanate) (MDI), BD and polyadi‐ pate diol were prepared by Pretsch (Pretsch et al., 2009) and accelerated degradation studied in distilled water at 80˚C where the degradation process was followed by DSC. It was found that the intensities of the melting peaks and therefore the crystallinity of the soft segments

**Table 2.** Polyurethane mass loss (%) after degradation under hydrolytic and oxidative accelerated conditions

compared with polyether or polycarbonates (Ma et al., 2012).

weight was reported.

**H2O NaOH 5M HCl 2N H2O2 30 wt.%**

weight loss (Mondal et al., 2012).

60 Advances in Biomaterials Science and Biomedical Applications

Polyether urethanes (PEU) are readily degraded by oxidative conditions (Stachelek et al., 2006). Furthermore, the presence of metallic ions such as cobalt accelerates this process (Gu‐ natillake et al., 1992; Dumitriu, 2002; Santerre et al., 2005). The MIO mechanism was repro‐ duced *in vitro* by immersing a lead into a hydrogen peroxide solution. In a different *in vitro* test, a sealed PEU tube containing cobalt metal in the center was immersed into a 3% hydro‐ gen peroxide solution and MIO was observed on the inner surface of the tube. The cobalt ion and hydrogen peroxide react to form hydroxyl radicals, simulating the oxidative radi‐ cals present at the material-macrophage interface.

Takahara et al. (Takahara et al., 1991) degraded SPU´s based on MDI, BD (50% rigid seg‐ ment content) and various polyols using 0.1 M AgNO3 oxidative solution. They found a re‐ duction in mechanical strength of those SPU´s based on PTMO due to surface cracking related to ether scission upon oxidation.

Suntherland et al. (Sutherland et al., 1993) degraded Pellethane 2363 80A using 10 mM HClO in phosphate buffer (PB) at 25°C. In addition, peroxynitrite (ONOO-) degradation was achieved via the oxidation of hydroxylamine in an oxygen atmosphere at elevated pH. They observed a significant reduction in molecular weight, increase in polydispersity index and an increasing content of oxygenated species on the polymer surface.

Tanzi et al. (Tanzi et al., 2000) studied the oxidative degradation of polyether (Pellethane 2363 80A) and polycarbonate (Corethane 80A, Bionate 80A and Chronoflex AL 80A) ure‐ thanes in 0.5 N nitric acid (acidic) and sodium hypochlorite (4% Cl2, alkaline) up to 14 days at 50˚C and under constant strain (100%). It was found that PEU were more degraded under alkaline oxidation (HClO) mainly in the absence of applied strain while PCU was more af‐ fected by HNO3.

Our own work using Tecoflex as model PEU degraded in H2O2 did not show signifi‐ cant changes in FTIR absorptions and only small differences in the bands located at 3330 cm-1 and 1660 cm-1 were observed (see Figure 3), although this was clear when the polyol was tested alone. However, TGA revealed that their degradation temperature were lowered and the amorphous content determined by XRD only exhibited a little changes (Chan-Chan et al., 2010).

**Figure 3.** Chemical and structural changes in Tecoflex after degradation under oxidative conditions

#### **4.3. Degradation in physiological media**

Poly(ester urethane)urea (PEUU) and poly(ether ester urethane)urea (PEEUU) from poly‐ caprolactone, polycaprolactone-b-polyethylene glycol-b-polycaprolactone, BDI and putres‐ cine were prepared by Guan et al. (Guan et al., 2005a) and degraded in phosphate buffered saline (PBS, pH=7.4) at 37˚C; scaffold degradation was related to the porosity and polymer hydrophilicity. The scaffolds exhibited progressive mass loss over the 8-week period rang‐ ing from 13.3% to 20.7% for PEUU scaffolds and from 25.4% to 47.3% for PEEUU scaffolds. In this study, the polymer films and scaffolds did not show evidence of an autocatalytic ef‐ fect during the monitored degradation process. Furthermore, the presence of BDI and 1,4 butanediamine in the hard segment of PU yielded putrescine as degradation product, which is already present in the body and has been implicated as an important mediator of cellular growth and differentiation in response to growth factors.

Our own work using Tecoflex as model PEU degraded in H2O2 did not show signifi‐ cant changes in FTIR absorptions and only small differences in the bands located at 3330 cm-1 and 1660 cm-1 were observed (see Figure 3), although this was clear when the polyol was tested alone. However, TGA revealed that their degradation temperature were lowered and the amorphous content determined by XRD only exhibited a little

**Figure 3.** Chemical and structural changes in Tecoflex after degradation under oxidative conditions

Poly(ester urethane)urea (PEUU) and poly(ether ester urethane)urea (PEEUU) from poly‐ caprolactone, polycaprolactone-b-polyethylene glycol-b-polycaprolactone, BDI and putres‐ cine were prepared by Guan et al. (Guan et al., 2005a) and degraded in phosphate buffered saline (PBS, pH=7.4) at 37˚C; scaffold degradation was related to the porosity and polymer hydrophilicity. The scaffolds exhibited progressive mass loss over the 8-week period rang‐ ing from 13.3% to 20.7% for PEUU scaffolds and from 25.4% to 47.3% for PEEUU scaffolds. In this study, the polymer films and scaffolds did not show evidence of an autocatalytic ef‐ fect during the monitored degradation process. Furthermore, the presence of BDI and 1,4 butanediamine in the hard segment of PU yielded putrescine as degradation product, which

**4.3. Degradation in physiological media**

changes (Chan-Chan et al., 2010).

62 Advances in Biomaterials Science and Biomedical Applications

Two gelatin based poly(ester urethane) were prepared by Sarkar et al. (Sarkar et al., 2006) using polyethylene lactate ester diol as a soft segment, and degraded in phosphate buffer saline solution (pH 7.4) at 37°C in a Biochemical Oxygen Demand (BOD) incubator shaker. It was found that the weight loss (up to 45.7% in 30 days) occurred due to the hydrolytic deg‐ radation of the gelatin based polyester urethane scaffold by PBS solution and it was propor‐ tional to the gelatin content.

Sarkar et al. (Sarkar et al., 2008) prepared segmented polyurethanes using polyethylene gly‐ col (PEG) or poly caprolactone diol (PCL) as the soft segment while hexamethylene diiso‐ cyanate (HDI) or dicyclohexylmethane 4,4-diisocyanate (HMDI) were used with desaminotyrosyl tyrosine hexyl ester (DTH) as the chain extender in the rigid component. For degradation in PBS (0.1M, pH 7.4 containing 200 mg of sodium azide) samples were in‐ cubated at 37˚C. It was found that PEG-based polyurethanes degrade at a faster rate com‐ pared with PCL-based polyurethanes due to their hidrophillicity and that this effect was marked when using high molecular weight PEG. It was also found that more amorphous SPU (i.e. exhibiting more phase mixing and therefore more urethane linkages H-bonded with the soft segment), such as those prepared with HMDI, degrade faster as they absorb more water.

Knight et al. (Knight et al., 2008) studied new hybrid thermoplastic polyurethane (TPU) sys‐ tem that incorporates an organic, biodegradable poly(D,L-lactide) soft block with a hard block bearing the inorganic polyhedral oligosilsesquioxane (POSS) moiety and degraded them in PBS buffer at 37 °C over a 2 months period. They found that less than 4% of the original mass elutes from the sample after a month in the buffer, most likely from chain ends on the surface of the sample undergoing hydrolysis. Although only a small mass loss was observed, the molecular weight of the samples dropped dramatically after only one week to 40% of the initial molecular weight.

Biodegradable ionic polyurethanes (PUs) were synthesized from methylene di-p-phenyl-dii‐ socyanate (MDI), polycaprolactone diol (PCL-diol) and N,N-bis (2-hydroxyethyl)-2-amino‐ ethane-sulfonic acid (BES) by Zhang et al. (Zhang et al., 2008). *In vitro* degradation of the PUs was evaluated by recording the samples' weight loss, molecular weight changes, and mechanical properties changes over time in PBS buffer solution at 67°C to accelerate degra‐ dation. Although there was a 20% molecular weight reduction, degradation rate was lower in those PUs containing sulfonic acid compared to PU´s without this chain extender. This was explained in terms of their higher phase separation.

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) were degraded *in vitro* (0.1 M phosphate buffered saline at 37°C in a shaken incubator set at 50 rpm (ASTM F 1635)) over a 1 year period (Zhang et al., 2008). It was found that all polyurethanes exhibited considerable mo‐ lecular weight decrease over the test period and ester chain extender polyurethanes showed the highest mass loss and that it was directly proportional to hard segment not to the PCL used as soft segment.

Guelcher et al. (Guelcher et al., 2008) prepared injectable polyurethanes by two-component reactive liquid molding of low-viscosity quasi-prepolymers derived from lysine polyisocya‐ nates and poly(3-caprolactone-co-DL-lactide-co-glycolide) triols and degraded porous discs by incubation in PBS at 37˚C and 5% CO2 for 2, 4, 6, and 8 months. They found that these polymers degrade by hydrolysis of ester linkages to yield α-hydroxy acids and soluble ure‐ thane fragments. Furthermore, the materials prepared from PCL triol exhibit minimal (e.g., <5%) degradation after 8 months. However, materials prepared from P6C3G1L (triol synthe‐ sized from a glycerol starter and a mixture of monomers comprising 60% caprolactone, 30% glycolide, and 10% DL-lactide) exhibit 15-27% mass loss after 8 months.

Multi-block poly(ether ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB), poly(propylene glycol) (PPG), and poly(ethylene glycol) (PEG) were prepared by Loh et al. (Loh et al., 2007). The poly(PEG/PPG/PHB urethane) copolymer hydrogels were hydrolyti‐ cally degraded in phosphate buffer at pH 7.4 and 37°C for a period of up to 6 months. The degradation products in the buffer were characterized by GPC, <sup>1</sup> H NMR, MALDI-TOF, and TGA. The results showed that the ester backbone bonds of the PHB segments were broken by random chain scission, resulting in a decrease in the molecular weight. In addition, the constituents of degradation products were found to be 3-hydroxybutyric acid monomer and oligomers of various lengths (n= 1–5).

Multiblock poly(ether ester urethane)s comprising of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments and hexamethylene diisocyanate were synthesized by Loh et al. (Loh et al., 2008). Their degradation process in pH 7.4 buffer solution (8.0 g of NaCl, 0.2 g of KCl, 1.44 g of Na2HPO4, and 0.24 g of K2H2PO<sup>4</sup> in 1 L of solu‐ tion) was studied over a period of 3 months. Multi-modal GPC profiles of these polymers suggested that the polymer degrades in fragments with molecular weight of about 2000, 4000, 6000 and 8000 g/mol. These gels degraded at a much faster rate than the previously reported PEG-PPG-PHB poly(ester urethane) thermogels, which were reported to degrade over a period of 6 months.

Degradation of segmented poly(urethane urea)s (SPUUs) with hard segments derived only from methyl 2,6-diisocyanatehexanoate (LDI) and PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA) or P(TMC-co-DLLA) as soft segment was conducted by Asplund et al. (Asplund et al., 2008). For the hydrolysis study, sterile and nonsterile samples were placed in 40 mL PBS buffer solution (pH 7.4) and put in an oven at 37˚C. Degradation was studied after 5, 10, 15, and 20 weeks and analyses performed in triplicate for each sample. The effect of sterilization was studied after 10 weeks of hydrolysis. Physical ageing was studied after 5 and 15 weeks at 50˚C. They found that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substan‐ tial reduction in intrinsic viscosity. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial loss in inherent viscosity and induced more rapid hydrolysis compared with nonsterilized samples, except for PUU-PTMC.

the highest mass loss and that it was directly proportional to hard segment not to the PCL

Guelcher et al. (Guelcher et al., 2008) prepared injectable polyurethanes by two-component reactive liquid molding of low-viscosity quasi-prepolymers derived from lysine polyisocya‐ nates and poly(3-caprolactone-co-DL-lactide-co-glycolide) triols and degraded porous discs by incubation in PBS at 37˚C and 5% CO2 for 2, 4, 6, and 8 months. They found that these polymers degrade by hydrolysis of ester linkages to yield α-hydroxy acids and soluble ure‐ thane fragments. Furthermore, the materials prepared from PCL triol exhibit minimal (e.g., <5%) degradation after 8 months. However, materials prepared from P6C3G1L (triol synthe‐ sized from a glycerol starter and a mixture of monomers comprising 60% caprolactone, 30%

Multi-block poly(ether ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] (PHB), poly(propylene glycol) (PPG), and poly(ethylene glycol) (PEG) were prepared by Loh et al. (Loh et al., 2007). The poly(PEG/PPG/PHB urethane) copolymer hydrogels were hydrolyti‐ cally degraded in phosphate buffer at pH 7.4 and 37°C for a period of up to 6 months. The

TGA. The results showed that the ester backbone bonds of the PHB segments were broken by random chain scission, resulting in a decrease in the molecular weight. In addition, the constituents of degradation products were found to be 3-hydroxybutyric acid monomer and

Multiblock poly(ether ester urethane)s comprising of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments and hexamethylene diisocyanate were synthesized by Loh et al. (Loh et al., 2008). Their degradation process in pH 7.4 buffer solution (8.0 g of NaCl, 0.2 g of KCl, 1.44 g of Na2HPO4, and 0.24 g of K2H2PO<sup>4</sup> in 1 L of solu‐ tion) was studied over a period of 3 months. Multi-modal GPC profiles of these polymers suggested that the polymer degrades in fragments with molecular weight of about 2000, 4000, 6000 and 8000 g/mol. These gels degraded at a much faster rate than the previously reported PEG-PPG-PHB poly(ester urethane) thermogels, which were reported to degrade

Degradation of segmented poly(urethane urea)s (SPUUs) with hard segments derived only from methyl 2,6-diisocyanatehexanoate (LDI) and PCL, PTMC, P(TMC-co-CL), P(CL-co-DLLA) or P(TMC-co-DLLA) as soft segment was conducted by Asplund et al. (Asplund et al., 2008). For the hydrolysis study, sterile and nonsterile samples were placed in 40 mL PBS buffer solution (pH 7.4) and put in an oven at 37˚C. Degradation was studied after 5, 10, 15, and 20 weeks and analyses performed in triplicate for each sample. The effect of sterilization was studied after 10 weeks of hydrolysis. Physical ageing was studied after 5 and 15 weeks at 50˚C. They found that the degradation rate was dependant on the soft segment structure, with a higher rate of degradation for the polyester-dominating PUUs exhibiting a substan‐ tial reduction in intrinsic viscosity. A tendency of reduction of tensile strength and strain hardening was seen for all samples. Also, loss in elongation at break was detected, for PUU-P(CL-DLLA) it went from 1600% to 830% in 10 weeks. Gamma radiation caused an initial

H NMR, MALDI-TOF, and

glycolide, and 10% DL-lactide) exhibit 15-27% mass loss after 8 months.

degradation products in the buffer were characterized by GPC, <sup>1</sup>

oligomers of various lengths (n= 1–5).

over a period of 6 months.

used as soft segment.

64 Advances in Biomaterials Science and Biomedical Applications

Yeganeh et al. (Yeganeh et al., 2007) prepared epoxy terminated polyurethanes from glyci‐ dol and isocyanate-terminated polyurethanes made from poly(*ε*-caprolactone) (PCL) or poly(ethylene glycol) (PEG) and 1,6-hexamethylene diisocyanate. Degradation studies were performed using tris buffered saline solutions (TBS; 0.05, 0*.*1molL−1 NaCl, pH 7.4) and incu‐ bated at 37°C up to 6 months. They observed that degradation rates correspond to their wa‐ ter-absorbing ability, with faster degradation in the more absorbent polymers while the weight loss, due to hydrolytic degradation, increased as the amount of PEG content in‐ creased. A possible explanation is that following dissolution of some PEG segments, there will be an increase in the porosity of the blends, leading to a greater surface area for water to access the ester bonds of hydrophobic PCL, which dominates the degradation rate. Other possible explanations include an increase in the hydrophilicity of the surface, which acceler‐ ates degradation, or an increase in the mobility of the PCL molecules, which could also facil‐ itate hydrolytic degradation. Also the rate of hydrolysis was raised with increasing time, which might result from the augmentation content of hydrophilic hydroxyl, amine, and car‐ boxylic groups generated at the surface during degradation.

Wang et al. (Wang et al., 2008) prepared novel biodegradable and biocompatible poly(esterurethane)s by *in situ* homogeneous solution polymerization of poly(3-caprolactone) diol, di‐ methylolpropionic acid (DMPA), and methylene diphenyl diisocyanate in acetone followed by solvent exchange with water. The hydrolytic degradation test was conducted on buffer solution (pH=7.4) at 37˚C up to 12 weeks and showed that the degradation rate was little affected by the DMPA content in the range investigated, but was observed to be influenced by the hard segment content.

Hong et al. (Hong et al., 2010) synthesized poly(ester carbonate)urethane ureas (PECUUs) using a blended soft segment of poly(caprolactone) (PCL) and poly(1,6-hexamethylene car‐ bonate) (PHC), 1,4- butane diisocyanate and putrescine as chain extender. They found that degradation of PECUUs in aqueous buffer (PBS at 37˚C) and subcutaneous implantation in rats (Adult female Lewis rats) was slower than poly(ester urethane)urea but faster than poly(carbonate urethane)urea (PCUU). Over a period of 56 days, poly(ether urethane)ureas (PEUU) exhibited a 9% mass loss in addition to a reduction in inherent viscosity, while all of the PECUUs and PCUU did not show detectable loss of mass. *In vivo* it was observed that the majority of the PEUU scaffold was degraded, and loose connective tissue occupied the implant area with few observed putative macrophages. For the PECUU 50/50 scaffolds, more remnant material was seen with darker violet staining of the putative infiltrating mac‐ rophages and fibroblasts.

Chan-Chan et al. (Chan-Chan, et al. 2012) synthesized new polyester poly(urethane-urea)s and their molecular weight changes during PBS degradation were monitored by gel perme‐ ation cromatography (GPC) (see Figure 4). Significant weight loss was not observed at six months but bulk degradation was corroborated by this analytical technique.

**Figure 4.** Molecular weight reduction in polyurethanes based on butanediamine (PUBDA), arginine (PUR), glycine (PUG) and aspartic acid (PUD).

#### **4.4. Enzymatic degradation**

Huang et al. (Huang et al., 1979) reported that a low molecular weight poly(ester-urea), poly(L-phenyl alanine/ethylene glycol/1,6-hexane diisocyanate), and a model diesterdiurea, dimethyl diphenyl alanine hexamethylene urea, were hydrolyzed by chymotrypsin at pH 8. They also observed degradation with papain latex (pH 6.5, PBS) of the model diesterdiurea.

Takahara et al. (Takahara et al., 1992) degraded SPU´s based on MDI, BD and various poly‐ ols using papain (80 U/mL) and papain activating solution (0.05 M cysteine, 0.02 EDTA, pH=6.5 ) in sodium acetate buffer solution. In this study it was found that PEO based poly‐ urethanes exhibited the larger mass loss from all the SPU´s studied in addition to a reduc‐ tion in Young´s modulus and tensile strength due to a reduction in molecular weight.

Labow et al. (Labow et al., 1996) degraded in elastase (from human neutrophils or pancreat‐ ic porcine) a poly(ester-urea-urethane) containing [14C]toluene diisocyanate (TDI), poly(cap‐ rolactone) and ethylenediamine as well as a poly(ether-urea-urethane) containing [14C]TDI, poly(tetramethylene oxide) and ethylenediamine (ED). They used neutrophils, which con‐ tain elastolytic activity, as they are present during the inflammatory response. Ten-fold more radioactive carbon was released when porcine pancreatic elastase was incubated with [14C]TDI/PCL/ED than when human neutrophil elastase was used. Ten-fold less radioactive carbon was released when [14C]TDI/PTMO/ED was incubated with porcine pancreatic elas‐ tase (PPE) as compared to [14C]TDI/PCL/ED. Radioactive carbon release data for [14C]TDI/PCL/ED polymer incubated with trypsin, a possible contaminant in pancreatic por‐ cine elastase showed no significant release of radioactive carbon by the same number of units of trypsin which would be present in the commercial PPE preparation used in the bio‐ degradation experiments.

Skarja and Woodhouse (Skarja et al., 2001) studied degradable segmented polyurethanes containing a phenylalanine diester chain extender and degraded them in buffer chymotryp‐ sin and trypsin solutions for up to 28 days. In this study it was found that the presence of phenylalanine resulted in an increased susceptibility to enzyme-mediated while the magni‐ tude of degradation and erosion was highly variable and was dependent on soft segment type (PCL or PEO) and molecular weight (500-2000 g/mol).

It is well-known that the segmented poly(urethane ureas) prepared from 4,4-diphenylme‐ thane diisocyanate, oligotetramethylene glycol, and diamines are not easily hydrolyzed by enzymes. This was further extended by Thomas and Jayabalan (Thomas et al., 2001) who re‐ ported that completely aliphatic poly(urethane urea) based on 4,4-methylene bis-cyclohexyl isocyanate/hydroxy terminated polybutadiene/1,6-hexamethylene diamine did not degrade in papain after 30 days at 37˚C.

Labow et al. reported that cholesterol esterase cleaved polyetherurethanes at the most prob‐ able site susceptible to hydrolytic cleavage, which is the urethane bonds, resulting in the re‐ lease of free amine (Labow et al., 2002). Santerre's group has also reported the degradation of polycarbonate polyurethanes with cholesterol esterase (Tang et al., 2002). Both the carbo‐ nate and urethane bonds were cleaved, resulting in many products ranging in molecular weight from 150 to 850 g/mol, as identified by GC–MS.

**Figure 4.** Molecular weight reduction in polyurethanes based on butanediamine (PUBDA), arginine (PUR), glycine

Huang et al. (Huang et al., 1979) reported that a low molecular weight poly(ester-urea), poly(L-phenyl alanine/ethylene glycol/1,6-hexane diisocyanate), and a model diesterdiurea, dimethyl diphenyl alanine hexamethylene urea, were hydrolyzed by chymotrypsin at pH 8. They also observed degradation with papain latex (pH 6.5, PBS) of the model diesterdiurea. Takahara et al. (Takahara et al., 1992) degraded SPU´s based on MDI, BD and various poly‐ ols using papain (80 U/mL) and papain activating solution (0.05 M cysteine, 0.02 EDTA, pH=6.5 ) in sodium acetate buffer solution. In this study it was found that PEO based poly‐ urethanes exhibited the larger mass loss from all the SPU´s studied in addition to a reduc‐

tion in Young´s modulus and tensile strength due to a reduction in molecular weight.

Labow et al. (Labow et al., 1996) degraded in elastase (from human neutrophils or pancreat‐ ic porcine) a poly(ester-urea-urethane) containing [14C]toluene diisocyanate (TDI), poly(cap‐ rolactone) and ethylenediamine as well as a poly(ether-urea-urethane) containing [14C]TDI, poly(tetramethylene oxide) and ethylenediamine (ED). They used neutrophils, which con‐ tain elastolytic activity, as they are present during the inflammatory response. Ten-fold more radioactive carbon was released when porcine pancreatic elastase was incubated with [14C]TDI/PCL/ED than when human neutrophil elastase was used. Ten-fold less radioactive carbon was released when [14C]TDI/PTMO/ED was incubated with porcine pancreatic elas‐ tase (PPE) as compared to [14C]TDI/PCL/ED. Radioactive carbon release data for [14C]TDI/PCL/ED polymer incubated with trypsin, a possible contaminant in pancreatic por‐

(PUG) and aspartic acid (PUD).

**4.4. Enzymatic degradation**

66 Advances in Biomaterials Science and Biomedical Applications

Yamamoto et al. (Yamamoto et al., 2007) degraded with different thiol proteases (papain, bromelain, and ficin) and Protease K and chymotrypsin, lysine diisocyanate (LDI) based poly(urethanes) and segmented poly(urethane ureas). For this, 1 mg of enzyme was added into the test tube coated with the polymer at 37˚C and the total organic carbon (TOC) meas‐ ured. From 1 H NMR results, it was evident that the pendant methyl ester group in LDI was rapidly hydrolyzed, followed by slow hydrolysis of urethane bonds in the backbone chain while the susceptibility of urea bonds to papain was very low. Before 50 h almost 30% of the PU has been degraded, with ethylene glycol exhibiting the highest rate of degradation; thiol proteases were most effective for all SPUUs. LDI/PTMO (Mw=2000 g/mol)/1,3-propylendia‐ mine (PDA) (2/1/1), which does not contain degradable soft segments (caprolactone block), showed degradation by various proteases. This fact strongly suggests that the cleavage of the hard segment (urethane and/or urea) by these proteases occurred. For the SPUU the ex‐ pected water-soluble degradation products are diamine, α-hydroxy caproic acid, and its low molecular oligomers, in addition to lysine derivatives.

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 measured the mass loss for 10 weeks at 37˚C. Polyurethane scaffolds were prepared by one-shot reactive liquid molding of hexam‐ ethylene diisocyanate trimer (HDIt) or lysine triisocyanate (LTI) and a polyol as hardener. Trifunctional polyester polyols of 900-Da molecular weight were prepared from a glycerol starter and 60% ε-caprolactone, 30% glycolide, and 10% D,L-lactide monomers (6C), (t1/2 = 20 days) and 70% caprolactone, 20% glycolide, and 10% lactide (7C) (t1/2 = 225 days) and stan‐ nous octoate catalyst. Incubation with esterases slightly accelerated degradation relative to PBS. Differences in degradation between the three candidate enzymes at any given time point were not significant. In contrast, incubation with medium that created an oxidative microenvironment had a more significant effect on the polyurethane degradation rate, espe‐ cially for the LTI-based materials, except the 6C/HDIt (hexamethylene diisocyanate trimer) + PEG, which interestingly degraded faster in the presence of cholesterol and carboxyl ester‐ ase than in oxidative medium.

A new family of water borne polyurethanes (WBPU) were synthesized by Jiang et al. (Jiang et al., 2007) using isophorone diisocyanate (IPDI), polycaprolactone (PCL), polyethylene gly‐ col (PEG) and BD:Lysine (1:1) as the chain extender. The polyurethane was then enzymati‐ cally degraded in PBS (pH = 7.4) with a solution mixture including PBS 60.0 ml, 0.1% MgC12 15.0 ml and Lipase AK (10 mg/ml) 15.0 ml and then incubated with shaking for certain time at 55˚C, which was the optimum temperature for enzyme activities of Lipase AK. An in‐ creased degradation was observed as decreasing of the amount of PEG in soft segments of WBPU, as judged from the change of tensile properties with time, owing to Lipase AK only interacting with PCL soft segments in these polymers structures. This result reveals that the degradation rate is proportional to the PCL content, and inverse proportion to the PEG con‐ tent in the WBPUs. Depending on the PCL content, degradation started even at 6 h in the presence of Lipase AK.

A polyurethane was synthesized with LDI, PCL, and BD in the presence of dilaurate as cata‐ lyst by Han et al. (Han et al., 2009) and then degraded in PBS with a solution mixture includ‐ ing 4.0 mL PBS, 1.0 mL 0.1 wt.% MgCl2 and 1.0 mL Lipase AK (10 mg/mL) in water at 50˚C. It was found that loss mass decreased with increasing the PCL soft segment content in hy‐ drolytic degradation in PBS. Because PCL is hydrophobic in comparison with the polar hard segment, increasing its content would decrease water uptake of PU films, and then decrease mass loss. In contrast, in the presence of Lipase AK the mass loss was observed to be in‐ creased with increasing the PCL soft segment content.

Biodegradable polyurethanes were prepared by Wang et al., using PLA-PEG-PLA as soft segment, and L-lysine ethyl ester diisocyanate (LDI) and 1,4-butanediol (BD) as rig‐ id segment (Wang et al., 2011b). These polymers were degraded in PBS (0.1 M PBS with 0.9% NaCl and 0.02% NaN3, pH 7.4, 6 and 5) and enzymatic (0.1mg/ml lipase from porcine pancreas in 0.1 M PBS with 0.9% NaCl and 0.02% NaN3, pH 7.4) solu‐ tions at 37 °C to simulate *in vivo* dynamic tissue environment. PU samples demonstrat‐ ed rapid degradation in 96 h (more than 90%) which might be attributed to hydrophilicity of PEG segments, low number-average molecular weight and microphase separation degree of these polyurethanes and enzyme functions. The enzymatic degra‐ dation rate was higher than hydrolytic degradation rate, verifying that Lipase from por‐ cine pancreas can accelerate hydrolysis on these polyurethanes.

A series of pH-sensitive biodegradable polyurethanes (pHPUs) were designed and synthe‐ sized using pH-sensitive macrodiol (poly(ε-caprolactone)-hydrazone-poly-(ethylene glycol) hydrazone-poly(ε-caprolactone) diol (PCL-Hyd-PEG-Hyd-PCL)), L-lysine ethyl ester diisocyanate (LDI) and L-lysine derivative tripeptide as chain extender by Zhou et al. (Zhou et al., 2011). The polyurethanes could be cleaved in acidic media (pH ∼ 4-6) as well as de‐ graded in PBS (100 mM, and pH 7.4) overnight at room temperature and enzymatic solution (Lipase AK (10 mg/mL, 2 mL) in PBS buffer solution with 0.1 wt % MgCl2 (2 mL) and then incubated with cyclic shaking at 52.5˚C). It was found that the hydrolysis rates of the two samples observed in Lipase AK PBS are higher than that in PBS i.e. 31.1% and 35.9% of weight loss are detected after hydrolytic and enzymatic degradation for 144 h of pHPU4 (pHPU prepared with LDI/macrodiol/tripeptide 3.15/2/1), respectively. The results indicate that the pHPUs are also facile to degrade in enzymatic solution, which is in agreement with reported literatures that Lipase AK is able to accelerate the PCL-based polymers biodegra‐ dation. Polymers with more pH sensitive macrodiol and lower crystallinity degraded even faster. The importance of studying these materials (pH-sensitive biodegradable polyur‐ ethanes) lies in the fact that they been used for intracellular multifunctional antitumor drug delivery (Zhou et al. 2012).

Elliott et al. (Elliott et al., 2002) determined mechanism of enzymatic degradation by HPLC/MS. Prior to product separation and identification, residual enzyme (chymotrypsin) was removed from the incubation solution samples. This process was necessary since the chymotrypsin could interfere with the accurate detection of the degradation products in the high performance liquid chromatography (HPLC) columns, and because proteins have a tendency to aggregate and then later precipitate during the gradient run, thereby causing additional difficulties in data acquisition. The results of the tandem mass spectrometry (MS/MS) analysis indicated that chymotrypsin may act to cleave urea bonds adjacent to Lphenylalanine residues. This is a significant finding since it confirms that the polyurethanes are susceptible to selective enzymatic degradation in the hard segment. Traditionally, this domain of the polyurethane has been considered a relatively stable group. The materials used in this study, however, were especially developed to encourage degradation of the hard segment rather than relying solely on degradation of the soft segment. Hence, the re‐ sults of this study confirm that this goal was achieved. The cleavage of urea bonds by chy‐ motrypsin is an important finding as it contradicts results of a previous study with similar chemistry that found that urea bonds adjacent to L-phenylalanine residues were not cleaved. However, since the level of chymotrypsin activity was not stated in the other study, it may be possible that the right conditions were not presented in order to degrade the urea bond (Elliott et al., 2002).

#### **4.5. Lipid degradation**

ethylene diisocyanate trimer (HDIt) or lysine triisocyanate (LTI) and a polyol as hardener. Trifunctional polyester polyols of 900-Da molecular weight were prepared from a glycerol starter and 60% ε-caprolactone, 30% glycolide, and 10% D,L-lactide monomers (6C), (t1/2 = 20 days) and 70% caprolactone, 20% glycolide, and 10% lactide (7C) (t1/2 = 225 days) and stan‐ nous octoate catalyst. Incubation with esterases slightly accelerated degradation relative to PBS. Differences in degradation between the three candidate enzymes at any given time point were not significant. In contrast, incubation with medium that created an oxidative microenvironment had a more significant effect on the polyurethane degradation rate, espe‐ cially for the LTI-based materials, except the 6C/HDIt (hexamethylene diisocyanate trimer) + PEG, which interestingly degraded faster in the presence of cholesterol and carboxyl ester‐

A new family of water borne polyurethanes (WBPU) were synthesized by Jiang et al. (Jiang et al., 2007) using isophorone diisocyanate (IPDI), polycaprolactone (PCL), polyethylene gly‐ col (PEG) and BD:Lysine (1:1) as the chain extender. The polyurethane was then enzymati‐ cally degraded in PBS (pH = 7.4) with a solution mixture including PBS 60.0 ml, 0.1% MgC12 15.0 ml and Lipase AK (10 mg/ml) 15.0 ml and then incubated with shaking for certain time at 55˚C, which was the optimum temperature for enzyme activities of Lipase AK. An in‐ creased degradation was observed as decreasing of the amount of PEG in soft segments of WBPU, as judged from the change of tensile properties with time, owing to Lipase AK only interacting with PCL soft segments in these polymers structures. This result reveals that the degradation rate is proportional to the PCL content, and inverse proportion to the PEG con‐ tent in the WBPUs. Depending on the PCL content, degradation started even at 6 h in the

A polyurethane was synthesized with LDI, PCL, and BD in the presence of dilaurate as cata‐ lyst by Han et al. (Han et al., 2009) and then degraded in PBS with a solution mixture includ‐ ing 4.0 mL PBS, 1.0 mL 0.1 wt.% MgCl2 and 1.0 mL Lipase AK (10 mg/mL) in water at 50˚C. It was found that loss mass decreased with increasing the PCL soft segment content in hy‐ drolytic degradation in PBS. Because PCL is hydrophobic in comparison with the polar hard segment, increasing its content would decrease water uptake of PU films, and then decrease mass loss. In contrast, in the presence of Lipase AK the mass loss was observed to be in‐

Biodegradable polyurethanes were prepared by Wang et al., using PLA-PEG-PLA as soft segment, and L-lysine ethyl ester diisocyanate (LDI) and 1,4-butanediol (BD) as rig‐ id segment (Wang et al., 2011b). These polymers were degraded in PBS (0.1 M PBS with 0.9% NaCl and 0.02% NaN3, pH 7.4, 6 and 5) and enzymatic (0.1mg/ml lipase from porcine pancreas in 0.1 M PBS with 0.9% NaCl and 0.02% NaN3, pH 7.4) solu‐ tions at 37 °C to simulate *in vivo* dynamic tissue environment. PU samples demonstrat‐ ed rapid degradation in 96 h (more than 90%) which might be attributed to hydrophilicity of PEG segments, low number-average molecular weight and microphase separation degree of these polyurethanes and enzyme functions. The enzymatic degra‐ dation rate was higher than hydrolytic degradation rate, verifying that Lipase from por‐

ase than in oxidative medium.

68 Advances in Biomaterials Science and Biomedical Applications

presence of Lipase AK.

creased with increasing the PCL soft segment content.

cine pancreas can accelerate hydrolysis on these polyurethanes.

Lipid absorption has been reported to occur in many medical devices such as heart valves made of silicon, leading to their calcification. In addition, fatigue properties of SPU have been reduced by lipid absorption.

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‐ ment as PEO based SPU´s were not affected.

#### **4.6. Compost biodegradation**

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‐ tion varied from 45 to 77% in 55 days.

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 was used led to a high degradation ratio.

#### **4.7. Thermal degradation of polyurethanes**

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 and hard segment ratio of polyurethanes.

The thermal degradation of polyurethanes allows determination of the proper conditions for manipulating and processing them and for obtaining high-performance products that are stable and free of undesirable by-products; if not processed properly, commonly by extru‐ sion or by injection moulding, the PU's would generate toxic products to the human body, which is very critical in biomedical applications [Gomes Lage et al. 2001].

It is well known that polyurethanes are not thermal stable polymers and that the onset deg‐ radation temperature of the urethane bond depends on the type of isocyanate and alcohol used. It is a general rule that the more easily formed polyurethanes are less stable, i.e. more easily dissociated when compared with more difficulty formed ones [Petrovic et al. 1994]. Petrovic reported that the degradation temperature for these materials ranged from 120°C to 250°C depending on their structure [Petrovic et al. 1994]; however, literature reports proc‐ essing temperatures closer to 180°C [Guignot 2002].

Polyurethanes are thermally degraded through three basic mechanisms. First, by urethane bond dissociation into its starting components (isocyanate and alcohol); secondly, by break‐ ing the urethane bond with formation of primary amines, carbon dioxide and olefins; and finally, splitting the urethane bond into secondary amine and carbon dioxide [Petrovic et al. 1994; Cervantes-Uc et al. 2009].
