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.     

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.     

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.     

Synthesis of segmented poly(ether urethane)s and poly(ether urethane urea)s incorporating various side-chain or backbone functionalities

A series of linear and branched functionalized high-molecular-weight segmented poly (ether urethane)s and poly(ether urethane urea)s were prepared by chain-extending isocyanate pre-polymers based on poly(tetramethylene oxide) with molecular weight 1000 and 4,4'-diphenylmethane diisocyanate. Different functional groups were incorporated within the polymer backbone or on side-chains by using several chain extenders during the synthesis: glycerol, 2,2-bis (hydroxymethyl) propionic acid, 1H, 1H,2H,3H,3H-perfluoroundecane-1,2-diol, 1H,1H,8H,8H-dodecanefluoro-1,8-octanediol, 1,3-diamino-2-hydroxypropane and 3,5-diaminobenzoic acid, using the method of gradual approach to stoichiometry. In some cases, pendant functional groups were used as reactive sites for the further attachment of side groups. Polymers were characterized using 1H-NMR and FT-IR spectroscopies and GPC in conjunction with chemical structural confirmation by a model compound comparison study of 4,4'-diphenylmethane diisocyanate or trifluoro-p-tolyl isocyanate reacted with 1,3-diamino-2-hydroxypropane and 1,4-butanediol.     

Thermal and mechanical properties of poly(ether urethane) modified by copolyamide segments

Thermoplastic polyurethane elastomers (TPUs) from diol-terminated poly(tetramethylene glycol) (PTMG), 1,4-butanediol (BD), and 4,4′-methylenediphenyl diisocyanate (MDI) were modified by copolymerizing diamine-terminated nylon-6/6,6 copolyamide oligomer. In TPUs modified by the copolyamide segment, the hard segment showed decreased crystallinity and melting point depression as the content of copolyamide segment was increased, which is probably due to mixing and strong interaction between copolyamide and hard segments. As some of the hard segments were replaced by copolyamide segments, the crystallinity of PTMG segments increased. This suggests that the copolyamide-PTMG segment interaction is weaker than the interaction between hard and PTMG segments. Tensile properties of TPUs are discussed based on the thermal properties.     

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.     

Studies of poly(ether)urethane pacemaker lead insulation oxidation

Published reports suggest that silver ions may catalyze the oxidation of poly(ether)urethane soft-segments resulting in the failure of urethane insulations of specific models of pacemaker leads. Attempted oxidation of soft-segment models, poly(tetra-methylene ether)glycols, by silver nitrate has shown that metal-ion catalyzed oxidative-reduction (MICOR) does not adequately explain observed failures unless antioxidants are removed in process. Such cracking can, however, be explained in terms of a metal ion enhanced environmental stress cracking.     

Synthesis,characterization and surface modification of low moduli poly(ether carbonate urethane)ureas for soft tissue engineering

Flexible scaffolds are of great interest in engineering functional and mechano-active soft tissues as such scaffolds might allow mechanical stimuli to transfer effectively from the scaffolds to cells during tissue development. Towards this end, we have developed a family of flexible poly(ether carbonate urethane)ureas (PECUUs) with a triblock copolymer poly(trimethylene carbonate)–poly(ethylene oxide)–poly(trimethylene carbonate) (PTMC–PEO–PTMC) or pentablock copolymers PTMC–PEO–PPO–PEO–PTMC (PPO, polypropylene oxide) as soft segments, linked by 1,4-diisocyanatobutane and putrescine. All of the PECUUs had low glass transition temperatures (<?46 °C). The PTMC–PEO–PTMC-containing PECUUs had low tensile strength and breaking strain. Replacing PEO with the similar length PEO–PPO–PEO resulted in highly flexible and soft PECUUs possessing breaking strains of 362–711%, tensile strengths of 8–18 MPa and moduli of 5.5–7.4 MPa at room temperature in air. Under aqueous conditions at 37 °C, these polymers remained flexible while their moduli were decreased to 3.4–4.0 MPa. PECUUs based on PTMC–PEO–PPO–PEO–PTMC were thermosensitive as the water content at 37 °C was lower than that at 4 °C. PECUU using PTMC–PEO–PTMC as a soft segment showed 30% weight loss over 6 weeks in PBS at 37 °C, while that using PTMC–PEO–PPO–PEO–PTMC as a soft segment had weight loss <6%. Degradation products were found to lack cytotoxicity. The mechanical stresses and moduli of PECUUs based on PTMC–PEO–PPO–PEO–PTMC were unchanged during the degradation. To enhance cell adhesion, PECUUs were surface modified with Arg-Gly-Asp-Ser (RGDS). Smooth muscle cell adhesion was 114% of tissue culture polystyrene for unmodified PECUU and >180% for RGDS-modified PECUUs, with cell viability on both surfaces increasing during culture. These low moduli polyurethanes may find applications in engineering cardiovascular or other soft tissues.     

Hydrolytic degradation of poly(carbonate)-urethanes by monocyte-derived macrophages

Polycarbonate (PCN)-based polyurethanes (PCNU) are rapidly becoming the chosen polyurethane (PU) for long-term implantation since they have shown decreased susceptibility to oxidation. However, monocyte-derived macrophages (MDM), the cell implicated in biodegradation, also contain hydrolytic activities. Hence, in this study, an activated human MDM cell system was used to assess the biostability of a PCNU, synthesized with 14C-hexane diisocyanate (HDI) and butanediol (BD), previously shown to be susceptible to hydrolysis by cholesterol esterase (CE). Monocytes, isolated from whole blood and cultured for 14 days on polystyrene (PS) to mature MDM, were gently trypsinized and seeded onto 14C-PCNU. Radiolabel release and esterase activity, as measured with p-nitrophenylbutyrate, increased for almost 2 weeks. At 1 week, the increase in radiolabel release and esterase activity were diminished by more than 50% when the protein synthesis inhibitor, cycloheximide, or the serine esterase/protease inhibitor, phenylmethylsulfonylfluoride was added to the medium. This strongly suggests that in part, it was MDM esterase activity which contributed to the PU degradation. In an effort to simulate the potential combination of oxidative and hydrolytic activities of inflammatory cells. 14C-PCNU was exposed to HOCl and then CE. Interestingly, the release of radiolabeled products by CE was significantly inhibited by the pre-treatment of PCNU with HOCl. The results of this study show that while the co-existing roles of oxidation and hydrolysis in the biodegradation of PCNUs remains to be elucidated, a clear relationship is drawn for PCNU degradation to the hydrolytic degradative activities which increase in MDM during differentiation from monocytes, and during activation in the chronic phase of the inflammatory response.     

Investigation of the durability of poly(ether urethane) in water and air

In this study some relevant aspects of the durability of an aromatic poly(ether urethanes) was investigated. Hydrolytic and oxidative treatments at increased temperatures were applied. The induced changes in the materials under investigation were characterised by complementary polymer characterisation methods, such as ATR-FTIR, DSC and mechanical testing. The thermal and hydrolytic treatment did not significantly affect the chemical composition of the materials. Changes can be observed in the microstructure of the materials.     

Primary thermal degradation processes of poly(ether/ketone) and poly(ether ketone)/poly(ether-sulfone) copolymers investigated by direct pyrolysis-mass spectrometry

The mechanisms of thermal degradation of poly(ether-ketone) (PEK) and four poly(ether-ketone)/poly(ether-sulfone) copolymers (PEK/PES) have been investigated by direct pyrolysis-mass spectrometry (DPMS). Several families of pyrolysis compounds with H, OH and CHO end-groups have been identified in the pyrolysis mass spectra of PEK. All these pyrolysis compounds can arise from degradation mechanisms involving cleavages of the bridged groups (diphenyl ether and dibenzophenone units). Our data show that the main degradation products of PEK are aldehydes, most likely formed by an intramolecular thermal cleavage of benzophenone units. Compounds containing dibenzofuran units have also been observed in the DCI mass spectrum of PEK. The thermal decomposition of a low molecular weight PEK sample occurs in two stages with the maxima of decomposition at 390°C and 490°C, respectively. This fact indicates the occurrence of an end-group initiated thermal decomposition in the early degradation stage which is not present in the case of the high molecular weight PEK sample. The pyrolysis of PEK does not produce compounds containing biphenyl units, indicating that extrusion of carbonyls or recominbation processes are not involved. The thermal degradation compounds of the PEK/PES copolymers originate from the thermal cleavage of the bridge groups (diphenyl ether, benzophenone and diphenyl sulfone). The pyrolysis mass spectra of 1:1 (alt.), 1:1 (random), 3:1 and 1:3 PEK/PES copolymers appear essentially identical (apart for obvious differences in peak intensities), indicating that the molecular rearrangements (SO₂ extrusion, transesterification, cleavage of bridges) which occur at higher temperatures and/or in the pyrolysis processes are able to randomize the distribution of comonomer units originally present in the copolymers. Differences in peak intensities have been found to reflect almost quantitatively the molar composition of the copolymers.     

Enzymatic degradation behavior and mechanism of poly(lactide-co-glycolide) foams by trypsin

The purpose of this study is to investigate the enzymatic degradation behaviors of porous poly(lactide-co-glycolide) (PLGA) foams in the presence of trypsin, in comparison with their hydrolytic degradation. To inspect the effect of trypsin on the degradation of PLGA, both the hydrolytic and enzymatic degradation of non-porous PLGA samples were also performed. The changes of molecular weight and molecular weight distribution (polydispersity) during the degradation were determined by gel permeation chromatograph. And the changes of weight, thickness and morphology with the degradation were also measured. The degradation of PLGA displayed as two stages. In the first stage, the molecular weight of PLGA decreased continuously with degradation time, whereas little weight loss occurred. But in the second stage, the molecular weight of PLGA had decreased to a low value and was almost unchanged with time, while the sample experienced significant weight loss. And it was found that the presence of trypsin could significantly accelerate the weight loss rates of all the PLGA samples, but it caused little difference in the decrease of molecular weight and the change of PLGA composition between the enzymatic and hydrolytic degradation. Therefore, the enzymatic degradation of PLGA was still primarily a hydrolysis process. A mechanism of enzymatic degradation was proposed that the trypsin could enhance the weight loss of PLGA by acting as surfactant to push the dispersion of degradation products into water even though they could not dissolve in water.     

Modification of poly(ether urethane)elastomers by incorporation of poly(isobutylene)glycol. Relation between polymer properties and thrombogenicity

Non-polar hydrophobic poly(isobutylene)glycol (PIBG) was substituted for poly(tetramethylene ether)glycol (PTMEG) in poly(ether urethanes) based on 4,4'-methylenebis-(phenylisocyanate) (MDI) and 1,4-butanediol (BD) as chain extender. Two series of polyurethanes differing in their soft segment length, polymer composition, and hard segment content were studied by dynamic mechanical analysis (DMA) and static, as well as dynamic, contact angle measurements. The thrombogenicity of these polymers was characterized by studying the adhesion and activation of platelets using ELISA for GMP 140 and fluorescence microscopy. It was found by DMA that in PIBG-containing polyurethanes (PUE) exist soft domains containing hard segments, strictly separated hard segment domains, and hard segments partially mixed with soft segments. Contact angle measurements revealed that 25% PIBG or even less, are sufficient for a remarkable enrichment of these non-polar soft segments on the polymer surface. The platelet adhesion/activation on these materials was demonstrated to increase with the rise in hard segment content, as well as with an enhancement of the PIBG content. However, comparison of PIBG-containing PUE with medical applied polypropylene and pellethane expressed that PUE with PIBG content equal or less 25% have excellent haemocompatibility.     

Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymer-modified poly(ether urethane) surfaces

A tri-block-coupling polymer of stearyl poly(ethylene oxide)-4,4'-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide) (MSPEO), was used as a surface modifying additive (SMA) and the MSPEO-modified poly(ether urethane) (PEU) surfaces were prepared by the process of dip-coating. The surface analysis by XPS revealed the surface enrichment of poly(ethylene oxide) (PEO). On the coating-modified surfaces, the bovine serum albumin (BSA) adsorption, respectively, from the low and high BSA bulk concentration solutions was correspondingly characterized by the methods of radioactive 125I-probe and ATR-FTIR. The bovine serum fibrinogen (Fg)-adsorption from the Fg bulk solution and the BSA-Fg competing adsorption from the BSA-Fg binary solutions were also characterized by radioactive 125I-probe. The reversible BSA-selective in situ adsorption on MSPEO-modified PEU surfaces were achieved, and the performance of blood compatibility on the coating-modified surfaces was also confirmed, respectively, by plasma recalcification time (PRT) and prothrombin time (PT) tests.     

The influence of protein adsorption and surface modifying macromolecules on the hydrolytic degradation of a poly(ether-urethane) by cholesterol esterase

Previous investigations have demonstrated that the inflammatory cell derived enzyme, cholesterol esterase (CE) could degrade polyurethanes (PUs) by hydrolyzing ester and urethane bonds. Studies that have investigated the development of protective coatings for PUs have reported that the polymer degradation of polyester-urethanes (PESUs) can be reduced with the use of fluorine containing surface modifying macromolecules (SMMs). Since these latter studies were carried out in the presence of relatively pure enzyme, it has not been shown if SMMs would still provide an enhanced inhibitory effect if surfaces were pre-exposed to plasma proteins. This would be more representative of the in vivo scenario since protein adsorption would occur before the appearance of monocyte-derived macrophages which would be a primary source of esterase activities. The current investigation has focused on studying the influence of fibrinogen (Fg) as a simple model of protein adsorption in order to assess the effect of CE in combination with protein on polyether-urethane (PEU) surfaces. The materials were prepared with and without SMMs, and were pre-coated with Fg prior to carrying out biodegradation studies. The pre-adsorption of Fg onto the modified and non-modified surfaces provided a significant delay in the hydrolytic action of CE onto the PEU substrates. However, the effect was gone by 70 days and by the 126th day of incubation, both Fg coated and non-Fg coated groups had the same level of degradation. The difference between Fg coated and non-coated substrates was much smaller for materials containing SMMs. In addition, the pre-adsorption of Fg did not alter the SMMs' ability to provide a more biostable surface over the 4 month incubation period.     

Selective binding of albumin on stearyl poly(ethylene oxide) coupling polymer-modified poly(ether urethane) surfaces

A tri-block-coupling polymer of stearyl poly(ethylene oxide)-4,4′-methylene diphenyl diisocyanate-stearyl poly(ethylene oxide)(MSPEO), was used as a surface modifying additive (SMA) and the MSPEO-modified poly(ether urethane) (PEU) surfaces were prepared by the process of dipcoating. The surface analysis by XPS revealed the surface enrichment of poly(ethylene oxide) (PEO). On the coating-modified surfaces, the bovine serum albumin (BSA) adsorption, respectively, from the low and high BSA bulk concentration solutions was correspondingly characterized by the methods of radioactive ¹²⁵I-probe and ATR-FTIR. The bovine serum fibrinogen (Fg)-adsorption from the Fg bulk solution and the BSA-Fg competing adsorption from the BSA-Fg binary solutions were also characterized by radioactive ¹²⁵I-probe. The reversible BSA-selective in situ adsorption on MSPEO-modified PEU surfaces were achieved, and the performance of blood compatibility on the coating-modified surfaces was also confirmed, respectively, by plasma recalcification time (PRT) and prothrombin time (PT) tests.     

Enzymatic degradation of microbial poly(3-hydroxybutyrate) films

The effects of crystallinity and spherulite size on the enzymatic degradation of microbial poly(3-hydroxybutyrate) (PHB) films have been studied at 37°C and pH 7,4 in aqueous solutions of an extracellular PHB depolymerase from Alcaligenes faecalis T1. The rate of enzymatic degradation of PHB films decreases with an increase in crystallinity, but it is little influenced by the size of PHB spherulites. It was suggested that the PHB depolymerase firstly hydrolyzes the PHB chains in the amorphous state on the surface of the films and subsequently erodes the PHB chains in the crystalline state.     

Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility

Polymers with elastomeric mechanical properties, tunable biodegradation properties and cytocompatibility would be desirable for numerous biomedical applications. Toward this end a series of biodegradable poly(ether ester urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers were synthesized and characterized. Poly(ether ester) triblock copolymers were synthesized by ring-opening polymerization of epsilon-caprolactone with polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low glass transition temperatures and possessed tensile strengths ranging from 8 to 20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing poly(caprolactone) length in the triblock segment increased PEEUU water absorption and biodegradation rate. Human umbilical vein endothelial cells cultured in a medium supplemented with PEEUU biodegradation solution suggested a lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was less than 60% of tissue culture polystyrene and was inversely related to PEEUU hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly-Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture polystyrene. These biodegradable PEEUUs thus possessed properties that would be amenable to applications where high strength and flexibility would be desirable and exhibited the potential for tuning with appropriate triblock segment selection and surface modification.     

PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers

Aiming at developing biodegradable thermo-responsive polymers that display enhanced rheological properties, a family of PEO-PPO-PEO based poly(ether ester urethane)s, was developed. The materials were produced following a two-step synthetic pathway. The PEO-PPO-PEO triblocks were first end-capped with LA or CL oligo(ester)s whereby pentablocks were produced. Then, the different precursors were chain extended using hexamethylene diisocyanate to create the respective polymers. The length and type of the ester block influenced the behavior of the molecules in water, especially their viscosity versus temperature response. The gelation temperature increased from 23 degrees C for a 20wt% F127 solution to 26 and 31 degrees C for pentablocks with 4.4 and 7.5 lactoyl units, respectively. Materials containing longer LA units failed to show any reverse thermo-responsiveness. The presence of the oligo(ester) blocks also reduced the viscosity of the gel at 37 degrees C. While F127 displayed a viscosity of around 28,000Pas, pentablocks containing 4.4 and 7.5 LA units showed values of 15,400 and 12,600Pas. Also, the viscosity at 37 degrees C as well as the gelation temperature decreased as the molecular weight of the oligo(ester)s increased. Finally, the degradation process of the gels was studied by monitoring their viscosity at body temperature and determining the molecular weight of the polymers, over time. Polymers were tailored so to combine high initial viscosity values with diverse degradation rates, as a function of the length and type of the oligo(ester) present along the polymeric backbone.     

Biodegradable thermogelling poly(ester urethane)s consisting of poly(lactic acid)--thermodynamics of micellization and hydrolytic degradation

Multiblock poly(ether ester urethane)s comprising of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized, and their aqueous solutions exhibited thermogelling behavior at critical gelation concentrations (CGC) ranging from 7 to 9 wt%. The chemical structures and molecular characteristics of the copolymers were studied by GPC, 1H NMR, 13C NMR and FTIR. The thermal stability of the poly(PEG/PPG/PLA urethane)s was studied by thermogravimetry analysis (TGA), and the PLA contents were calculated based on the thermal degradation profile. The results were in good agreement with those obtained from the 1H NMR measurements. The critical micellization concentration (CMC) of these water-soluble poly(ether ester urethane)s was determined at different temperatures using a dye solubilization method. The thermodynamic parameters for micelle formation were calculated, indicating that the process is largely entropy-driven. Interestingly, it appears that there exists a requirement for the system to possess a minimum gain in entropy before the thermogelling effect can be observed. Dilute copolymer solutions showed a lower critical solution temperature (LCST) behavior similar to pNIPAM dissolved in aqueous solutions. The thermogels hydrolytically degraded to polymer fragments corresponding to the constituent segment blocks within 3 months.