Poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo studies

Several strategies have been used to increase the biostability of medical-grade polyurethanes while maintaining biocompatibility and mechanical properties. One approach is to chemically modify or replace the susceptible soft segment. Currently, poly(carbonate urethanes) (PCUs) are being evaluated as a replacement of poly(ether urethanes) (PEUs) in medical devices because of the increased oxidative stability of the polycarbonate soft segment. Preliminary in vivo and in vitro studies have reported improved biostability of PCUs over PEUs. Although several studies have reported evidence of in vitro degradation of these new polyurethanes, there has been no evidence of significant in vivo degradation that validates a degradation mechanism. In this study, the effect of soft segment chemistry on the phase morphology, mechanical properties, and in vivo response of commercial-grade PEU and PCU elastomers was examined. Results from dynamic mechanical testing and infrared spectroscopy suggested that the phase separation was better in PCU as compared with PEU. In addition, the higher modulus and reduced ultimate elongation of PCU was attributed to the reduced flexibility of the polycarbonate soft segment. Following material characterization, the in vivo biostability and biocompatibility of PEU and PCU were studied using a subcutaneous cage implant protocol. The results from the cage implant study and cell culture experiments indicated that monocytes adhere, differentiate, and fuse to form foreign body giant cells on both polyurethanes. It is now generally accepted that the reactive oxygen species released by these adherent macrophages and foreign body giant cells initiate PEU biodegradation. Attenuated total reflectance-Fourier transform infrared analysis of explanted samples provided evidence of chain scission and crosslinking in both polyurethanes. This indicated that the PCU was also susceptible to biodegradation by agents released from adherent cells. These results reinforce the need to evaluate and understand the biodegradation mechanisms of PCUs.     

Enzymatic degradation of poly(ether urethane) and poly(carbonate urethane) by cholesterol esterase

This study examined the effect of cholesterol esterase (CE) on the degradation of commercial poly(ether urethane) (PEU) and poly(carbonate urethane) (PCU). Unstrained PEU and PCU films were incubated in 400 U/mL CE solution or a buffer control for 36 days. The study used a concentration of cholesterol esterase that was considerably higher than the estimated physiological level in order to accelerate degradation. However, characterization of treated polyurethane films with SEM, attenuated total reflectance Fourier transform infrared (ATR-FTIR) and GPC analysis revealed only a small loss in surface soft segment content. Comparison with implanted PEU and PCU films led to the conclusion that any effect of enzymatic hydrolysis was confined to the immediate surface, and the magnitude of the effect was too small to contribute significantly to in vivo degradation. The study confirmed that oxidation, rather than enzymatic hydrolysis, is the primary mechanism responsible for the observed biodegradation of PEU and PCU. The oxidative H(2)O(2)/CoCl(2) treatment continues to accurately predict the long-term biostability of polyurethanes.     

Biostability and macrophage-mediated foreign body reaction of silicone-modified polyurethanes

In this study, the effect of soft segment chemistry on the phase morphology and in vivo response of commercial-grade poly(ether urethane) (PEU), silicone-modified PEU (PEU-S), poly(carbonate urethane) (PCU), and silicone-modified PCU (PCU-S) elastomers were examined. Silicone-modified polyurethanes were developed to combine the biostability of silicone with the mechanical properties of PEUs. Results from the infrared spectroscopy confirmed the presence of silicone at the surface of the PEU-S and PCU-S films. Atomic force microscopy phase imaging indicated that the overall two-phase morphology of PEUs, necessary for its thermoplastic elastomeric properties, was not disrupted by the silicone modification. After material characterization, the in vivo foreign body response and biostability of the polyurethanes were studied using a subcutaneous cage implant protocol. The results from the cage implant study indicated that monocytes adhere, differentiate to macrophages which fuse to form foreign body giant cells on all of the polyurethanes. However, the silicone-modified surfaces promoted apoptosis of adherent macrophages at 4 days and high levels of macrophage fusion after 21 days. These results confirm that the surface of a biomaterial may influence the induction of apoptosis of adherent macrophages in vivo and are consistent with previous cell culture studies of these materials. This study validates the use of our standard cell culture protocol to predict in vivo behavior and further supports the hypothesis that interleukin-4 is the primary mediator of macrophage fusion and foreign body giant cell formation in vivo. The impact of these findings on the biostability of polyurethanes is the subject of current investigations. Attenuated total reflectance-Fourier transform infrared analysis of explanted specimens provided evidence of chain scission and crosslinking at the surface of all of the polyurethanes. The silicone modification did not fully inhibit the oxidative biodegradation of the polyether or polycarbonate soft segments; however, the rate of chain scission of PEU-S and PCU-S seemed to be slower than the control polyurethanes. To verify this finding and to quantify the rate of chain scission in order to predict long-term biostability, an in vitro environment that simulated the microenvironment at the adherent cell-material interface was used to accelerate the biodegradation of the polyurethanes. Polyurethane films were treated in vitro for up to 36 days in 20% hydrogen peroxide/0.1M cobalt chloride solution at 37 degrees Celsius. Characterization with attenuated total reflectance-Fourier transform infrared and scanning electron microscopy showed soft segment and hard segment degradation consistent with the chemical changes observed after long-term in vivo treatment. The biostability ranking of these four materials based on rate of chain scission and surface pitting was as follows: PEU < PEU-S PCU < PCU-S. The silicone modification increased the biostability of the PEU and PCU elastomers while maintaining the thermoplastic elastomeric properties.     

Oxidative mechanisms of poly(carbonate urethane) and poly(ether urethane) biodegradation: in vivo and in vitro correlations

This study used an in vitro environment that simulated the microenvironment at the adherent cell-material interface to reproduce and accelerate the biodegradation of poly(ether urethane) (PEU) and poly(carbonate urethane) (PCU). Polyurethane films were treated in vitro for 24 days in 20% hydrogen peroxide/0.1 M cobalt chloride solution at 37 degrees C. Characterization with ATR-FTIR and SEM showed soft segment and hard segment degradation consistent with the chemical changes observed after long-term in vivo treatment. Overall, the PCU underwent less degradation and the degraded surface layer was much thinner than PEU. Nevertheless, the results supported a common oxidation mechanism for biodegradation of these polymers. The observed in vitro degradation was inhibited by adding an antioxidant to the polyurethane film. Our findings further support the use of the in vitro H(2)O(2)/CoCl(2) system in evaluating the biostability of polyurethanes under accelerated conditions.     

Antioxidant inhibition of poly(carbonate urethane) in vivo biodegradation

This study compared the effect of an antioxidant on the in vivo biodegradation of a poly(carbonate urethane) (PCU) and a poly(ether urethane) (PEU). Unstrained PEU and PCU films with and without Santowhite were implanted subcutaneously into 3-month-old Sprague-Dawley rats for 3, 6, and 12 months. Characterization of unstabilized PEU and PCU with ATR-FTIR and SEM showed soft-segment and hard-segment degradation consistent with previous studies. In particular, evidence of chain scission and crosslinking of the surface was present in the ATR-FTIR spectra of explanted specimens. Addition of 2.2 wt % antioxidant inhibited the in vivo degradation of both PCU and PEU. Although the antioxidant probably improved polyurethane biostability by decreasing the susceptibility of the polymer to degradation, modulation of the cellular response to prevent the release of degradative agents was also possible. To differentiate the effects, the foreign-body response was investigated with the use of a standard cage implant protocol. Polyurethane films were implanted in wire mesh cages subcutaneously in rats for 4, 7, and 21 days. There were no statistical differences among materials in the inflammatory exudate cell counts, adherent cell densities, or percent fusion of macrophages into foreign-body giant cells (FBGCs). Therefore, it was concluded that the antioxidant inhibited degradation by capturing oxygen radicals that would otherwise cause polyurethane chain scission and crosslinking.     

In vitro oxidation of high polydimethylsiloxane content biomedical polyurethanes: correlation with the microstructure

The resistance to in vitro metal ion oxidation of a polydimethylsiloxane (PDMS)-containing thermoplastic polyurethane elastomer (Elast-Eon) is compared with that of a polyurethane consisting of the same hard segment chemistry and content, but with aliphatic polycarbonate soft segments (PCU). Scanning electron microscopy and attenuated total reflectance Fourier transform infrared spectroscopy were used to assess changes in surface morphology and chemistry. The extent of bulk degradation was assessed indirectly by dynamic mechanical analysis and small-angle X-ray scattering experiments. The findings indicate that Elast-Eon is more resistant to oxidation than the PCU, because of the presence of the PDMS soft segments as well as its phase separated microstructure. The PCU exhibits a rather high degree of intermixing between hard and soft segments, rendering the hard segments dissolved or trapped in the soft phase more susceptible to oxidative conditions. By contrast, we propose that the existence of a completely phase separated PDMS soft phase in Elast-Eon protects the remainder of the segments from oxidation.     

聚碳酸酯型聚氨酯的体外降解研究

本研究聚碳酸酯型聚氨酯(PCU),在预氧化处理后(5%H2O2/0.05M CoCl2溶液),再用酶(番木瓜蛋白酶,20U/ml的溶液)水解处理后的表面形态及分子结构变化,同时与聚醚聚氨酯(PEU)和氟碳化合物封端的聚碳酸酯型聚氨酯(PCUF)材料作对比。通过扫描电镜(SEM),光电子能谱(XPS)和分子量(GPC)表征材料表面降解情况和分子结构变化。结果证实了材料的抗氧化性能直接影响材料的整体降解情况,结果显示PCU抗氧化性能优良,所以它的整体抗降解能力比抗氧化能力较低的PEU强,而且在PCU中引入氟碳化合物,其抗降解能力会更强。     

Fluorocarbon chain end-capped poly(carbonate urethane)s as biomaterials: blood compatibility and chemical stability assessments

Previous work has shown the synthesis of fluorocarbon chain (CF(3)(CF(2))(6)CH(2)O-) end-capped poly(carbonate urethane)s (FPCUs) and confirmed the presence of a novel bilayered surface structure in FPCUs, that is, the top fluorocarbon and subsurface hard segment layers (Xie et al., J Biomed Mater Res Part A 2008; 84:30-43). In this work, the effects of such surface structure on blood compatibility were investigated using hemolytic test and platelet adhesion analysis. The chemical stability of the polymers was also determined by Zhao's glass wool-H(2)O(2)/CoCl(2) test and phosphate-buffered saline (PBS, pH = 3.1-3.3) treatment. One of the FPCUs, FPCU-A, and two control materials, a poly(ether urethane) (PEU) and a poly(carbonate urethane) (PCU), were investigated. No significant difference in hemolytic indices was observed among the three materials, whereas the adherent density and deformation of platelets were much lower on FPCU-A compared with on PCU and PEU. Severe surface cracking and surface buckling developed in prestressed PEU and PCU films after H(2)O(2)/CoCl(2) treatment, respectively, whereas smooth surface was observed for the FPCU-A. PBS incubation resulted in parallel ridge-like morphology in PCU whereas PEU and FPCU-A retained their smooth surfaces. Under relatively high stress conditions, all the materials developed well-oriented strip-like surface patterns. Results from ATR-FTIR spectra revealed a surface oxidation mechanism as described in literature. However, observations of universal decrease of molecular weights under stress conditions further suggested the presence of another bulk stress oxidation mechanism. Regardless the degradation mechanisms involved, the unique bilayered surface structure really improved the blood compatibility and chemical stability of FPCU-A, indicating that further in vivo investigations are worthwhile.     

Variations between Biomer lots. I. Significant differences in the surface chemistry of two lots of a commercial poly(ether urethane).

We have studied the surface chemistry of two lots of Biomer (BSP067 and BSUA001), a widely used commercial poly(ether urethane) (PEU). Although transmission infrared adsorption studies revealed no differences in the bulk chemistry of the two lots, the surface chemistry, as seen by x-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS), was different. Lot BSP067 showed soft-segment enrichment at the surface, which is typical of PEU. Lot BSUA001 showed no evidence of either hard- or soft-segment PEU components at the surface. The surface of this lot was completely covered with a nonextractable additive identified as poly(diisopropyl amino ethyl methacrylate). Small amounts of a low-molecular-weight antioxidant were observed at the surface of both samples. Because the biological response to polymers is dependent on surface structure, these results are of considerable importance to biomaterials research.     

Long-term in vivo biostability of poly(dimethylsiloxane)/poly(hexamethylene oxide) mixed macrodiol-based polyurethane elastomers

The long-term biostability of a novel thermoplastic polyurethane elastomer (Elast-Eon 2 80A) synthesized using poly(hexamethylene oxide) (PHMO) and poly(dimethylsiloxane) (PDMS) macrodiols has been studied using an in vivo ovine model. The material's biostability was compared with that of three commercially available control materials, Pellethane 2363-80A, Pellethane 2363-55D and Bionate 55D, after subcutaneous implantation of strained compression moulded flat sheet dumbbells in sheep for periods ranging from 3 to 24 months. Scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to assess changes in the surface chemical structure and morphology of the materials. Gel permeation chromatography, differential scanning calorimetry and tensile testing were used to examine changes in bulk characteristics of the materials. The results showed that the biostability of the soft flexible PDMS-based test polyurethane was significantly better than the control material of similar softness, Pellethane 80A, and as good as or better than both of the harder commercially available negative control polyurethanes, Pellethane 55D and Bionate 55D. Changes observed in the surface of the Pellethane materials were consistent with oxidation of the aliphatic polyether soft segment and hydrolysis of the urethane bonds joining hard to soft segment with degradation in Pellethane 80A significantly more severe than that observed in Pellethane 55D. Very minor changes were seen on the surfaces of the Elast-Eon 2 80A and Bionate 55D materials. There was a general trend of molecular weight decreasing with time across all polymers and the molecular weights of all materials decreased at a similar relative rate. The polydispersity ratio, Mw/Mn, increased with time for all materials. Tensile tests indicated that UTS increased in Elast-Eon 2 80A and Bionate 55D following implantation under strained conditions. However, ultimate strain decreased and elastic modulus increased in the explanted specimens of all three materials when compared with their unimplanted unstrained counterparts. The results indicate that a soft, flexible PDMS-based polyurethane synthesized using 20% PHMO and 80% PDMS macrodiols has excellent long-term biostability compared with commercially available polyurethanes.     

Effect of soft segment chemistry on the biostability of segmented polyurethanes. II. In vitro hydrolytic degradation and lipid sorption.

A series of segmented polyurethanes (SPUs) with various polyol soft segments was prepared and their hydrolytic degradation and degradation due to lipid sorption was investigated. The hydrolytic degradation of the SPUs was investigated in a papain solution, where it was shown that the SPU based on poly(ethyleneoxide) (PEO) soft segment was susceptible to hydrolytic degradation. X-ray photoelectron spectroscopic (XPS) data suggest dissociation of the urethane linkage by enzymatic degradation. Degradation by lipid sorption was observed for the SPU based on a poly(dimethylsiloxane) (PDMS) soft segment. This is ascribed to the high solubility of lipid in the PDMS segment of the SPU.     

Effect of soft segment chemistry on the biostability of segmented polyurethanes. I. In vitro oxidation

A series of segmented polyurethanes (SPUs) containing various polyol soft segments was prepared and their resistance to oxidative degradation was investigated after aging in AgNO3 solution. The SPU with the polyether soft segment showed a large reduction in mechanical strength after exposure to the oxidative environment. Surface cracking was often observed for these specimens. XPS measurements revealed that scission of the ether linkage occurs upon oxidation. The oxidative resistance of SPUs containing aliphatic hydrocarbon soft segments was significantly improved over the poly(tetramethylene oxide) (PTMO) based polyurethane.     

Synthesis and characterization of fluorocarbon chain end-capped poly(carbonate urethane)s as biomaterials: a novel bilayered surface structure

Poly(carbonate urethane)s (PCUs) are usually considered as biostable elastomers for long-term implantation. However, their hydrolytic stability is still questionable. The biodegradation appears to be initiated by oxidative and hydrolytic substances released by inflammatory cells. Therefore, the biostability of polyurethane might be improved with control of surface structure to reduce inflammatory response. A new type of PCUs end-capped with perfluoro chains was synthesized to explore a new avenue. A fluorinated alcohol, 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluoro-1-octanol (PDFOL), was end-capped to the backbones of PCUs by reaction of the --OH in PDFOL with the --NCO end groups in PCU backbones. Contact angle measurement, X-ray photoelectron spectroscopy, atomic force microscopy, and attenuated total reflectance-Fourier transform infrared spectroscopy were used to examine their surface structure and properties. Elemental analysis, gel permeation chromatography, differential scanning calorimetry, and tensile testing were used to assess bulk chemistry and properties. The fluorocarbon end-capped poly (carbonate urethane)s (FPCUs) maintained the high mechanical properties (about 40 MPa tensile strength) and typical microphase separation structure of polyurethane elastomers. Results from surface analyses revealed the presence of a double-layered structure at the surfaces of the FPCUs. The first one was composed of fluorocarbon tails rising up on the uppermost layer and the second one made up of hard-segments. This novel bilayered surface structure could protect the weak carbonate linkages in soft segments, and consequently, may potentially increase the biostability of this kind of polyurethanes.     

Analysis of in vitro enzymatic and oxidative degradation of polyurethanes

In vitro biodegradation studies were performed to assess the long-term stability of poly(ether urethane) (PEU) implants. Three PEU's and one poly(ester urethane) were treated with enzymes characteristic of those released from inflammatory cells during the foreign body reaction. In addition, the effect of hydrogen peroxide was observed to examine oxidative degradation. Polymers were prepared as thin films on glass, gold, silver, and copper substrates to test the possibility of metal-catalyzed degradation. Molecular weights and polydispersities of the polymers were measured by gel permeation chromatography (GPC) before and after treatment. Changes in peak shape and location were also monitored. The results demonstrate that varying degrees of both enzymatic and oxidative degradation occurred.     

In vitro degradation of a poly(ether urethane) by trypsin

In vitro enzymatic degradation of non-porous films of segmented poly(ether urethane) (Pellethane 2363-80AE) was investigated by incubating the biomaterial in concentrated trypsin solutions for 5 months at room temperature. Chemical degradation of films was monitored by surface analysis techniques such as Fourier transform infrared spectroscopy-attenuated total reflectance and electron spectroscopy for chemical analysis. This latter technique proved to be much superior in detecting chemical changes. Extraction of films with methanol and characterization of the extracts by gel permeation chromatography revealed the presence of low-molecular-weight polymers. Results have shown that trypsin has the ability to induce degradation in PEU, the soft segment being most affected, particularly the CH2-O bond of the ether linkages.     

The effect of virtual cross linking on the oxidative stability and lipid uptake of aliphatic poly(urethane urea).

In vitro oxidative degradation and lipid sorption of aliphatic, low elastic modulus and virtually cross-linked poly(urethane urea)s based on 4,4' methylene bis(cyclohexyl isocyanate), hydroxy terminated poly butadiene and hexamethylene diamine were evaluated. The aged samples revealed no weight loss in the oxidation medium. The IR spectral analyses revealed the stability of unsaturated double bonds at 964 cm(-1) (characteristic for polybutadiene soft segment) with no change in peak intensity. The poly(tetramethylene glycol) (PTMG)-added poly(ether urethane urea) polymer also revealed no disappearance of IR peaks for ether and unsaturated double bonds in samples aged in vitro oxidation medium. All the polymers have shown increase in weight due to lipid up take in lipid-rich medium (palm oil) but it was rather low in Dulbecco's modified eagle medium (DMEM) cholesterol. The slight change in mechanical properties of the present polymers in oxidation and DMEM is due to the rearrangement of molecular structure with virtual cross links of hydrogen bonding (physical cross linking) without degradation and plasticization effect of lipid. The influence of these media on the rearrangement of virtual cross links has been observed. Higher the virtual cross-link density, lesser is the loss of tensile properties of poly(urethane urea)s in the oxidation medium and vice versa. On the other hand, higher the virtual cross-link density of poly(urethane urea), higher is the loss of ultimate tensile strength and stress at 100% strain and vice versa in DMEM medium.     

Selective grafting of hydrogels onto multiphase block copolymers

Selective graft copolymerizations onto different segments of a poly(ether-urethane) (PEU) by using two different methods, i.e. ceric salt initiation and controlled oxidation, were investigated. By ceric salt initiation the grafting takes place mainly at the hard segment, while the controlled oxidation gives grafted hydrogels at the soft segment. The effects of different factors on graft copolymerization in both methods including ceric salt concentration, monomer concentration, PEU composition and oxidation time were investigated. Another kind of multiphase block copolymers, a poly(ether-ester), also can be graft-copolymerized by both methods.     

Biodegradation of polyether polyurethane inner insulation in bipolar pacemaker leads

Several bipolar coaxial pacemaker leads, composed of an outer silicone rubber insulation and an inner polyether polyurethane (PEU) insulation, which were explanted due to clinical evidence of electrical dysfunction, were analyzed in this study. Optical microscopy (OM) and scanning electron microscopy (SEM) were used to determine the cause of failure. Attenuated total reflectance-Fourier transform infrared microscopy (ATR-FTIR) was used to analyze the PEU insulation for chemical degradation. In all leads, the silicone rubber outer insulation showed no signs of physical damage. Physical damage to the inner PEU insulation was the source of electrical dysfunction. Cracks through the PEU compromised the insulation between the inner and outer conductor coils in the lead. It was observed with SEM that these cracks originated on the outer surface of the inner insulation and progressed inward. ATR-FTIR analysis showed that the PEU had chemically degraded via oxidation of the ether soft segment. Furthermore, it was revealed that chemical degradation was more advanced on the outer surface of the PEU. It was hypothesized that hydrogen peroxide permeated through the outer silicone insulation and decomposed into hydroxyl radicals that caused the chemical degradation of PEU. The metal in the outer conductor coil catalyzed the decomposition of the hydrogen peroxide. Chemical degradation of the PEU could also have been catalyzed by metal ions created from the corrosion of the metal in the outer conductor coil by hydrogen peroxide. Physical damage probably occurred in regions of the leads that were subjected to a higher hydrogen peroxide concentration from inflammatory cells and high degrees and rates of strain due to intercorporeal movement, including, but not limited to, cardiac movement. Chemical degradation and physical damage probably had a synergistic affect on failure of the insulation, in that as chemical degradation proceeded, the polymer surface became brittle and more susceptible to physical damage. As physical damage proceeded, cracks propagated into the unaffected bulk, exposing it to oxidants.     

Novel biostable and biocompatible amphiphilic membranes

We determined the biostability and biocompatibility of two types of amphiphilic conetworks (APCNs): (1) hydrophilic poly(N,N-dimethyl acrylamide) (PDMAAm) and hydrophobic polydimethylsiloxane (PDMS) microdomains co-crosslinked with polymethylhydrosiloxane (PMHS) clusters (PDMAAm/PMHS/PDMS), and (2) poly(ethylene glycol) (PEG) and PDMS microdomains co-crosslinked with two specially designed small-molecule crosslinking agents SiC(6)H(5)(SiH)(2)OEt (Y) and polypentamethylhydrocyclosiloxane (PD(5)) (PEG/Y or PD(5)/PDMS). Negative standards for comparing biocompatibility and biostability were crosslinked PDMS. Biostability was assessed by quantitatively determining extractables, equilibrium water swelling, mechanical properties (stress-strain response) of polymer samples before and after implantation in rats for up to 8 weeks, and oxidative accelerated degradation test. Biocompatibility was assessed by determining body weight, fibrous tissue encapsulation, fluid accumulation, and by histological evaluation of lymphocyte infiltration, fibrous tissue accumulation and collagen deposition. According to these stringent metrics PDMAAm/PMHS/PDMS is both biostable and biocompatible, whereas PEG/Y or PD(5)/PDMS degrades in living tissue but is biocompatible. Surprisingly, the overall biocompatibility scores of these APCNs were superior to those of the PDMS negative standard.     

Enzyme-induced biodegradation of polycarbonate polyurethanes: dependence on hard-segment concentration

Polycarbonate-based polyurethanes with varying hard segment contents were synthesized. The physical and chemical structures were characterized by using gel permeation chromatography, differential scanning calorimetry, water uptake testing, Fourier transform infrared, and attenuated total reflectance--Fourier transform infrared. The polymers were incubated with cholesterol esterase in a phosphate buffer solution at 37 degrees C over 10 weeks. A higher resistance to hydrolytic degradation was observed in polycarbonate-based urethanes with higher hard segment content. The analysis of the material structures revealed that the degradation of polycarbonate-based urethanes was preferentially initiated at non-hydrogen-bonded carbonates and urethanes. Although the crystallinity of the polycarbonate soft segment may contribute to reducing the hydrolytic degradation catalyzed by cholesterol esterase, it was found to be relatively minor in comparison to the importance of hydrogen bonding between the carbonate and urethane groups. These observations suggest that the biostability of polyurethanes and specifically polycarbonate-based polyurethanes can be improved by manipulating the degree of hydrogen bonding within the materials.