Segmented polyurethanes derived from novel siloxane–carbonate soft segments for biomedical applications

A novel macrodiol based on mixed silicone and carbonate chemistries was synthesized and used as a soft segment precursor in the synthesis of two series of segmented polyurethane (PU) copolymers varying in hard segment content and soft segment molecular weight. The hard segments in these copolymers were derived from 4,4‐methylene diphenyl diisocyanate and 1,4‐butane diol. The phase transitions, microphase separation behavior, and mechanical properties of the copolymers were investigated using a variety of experimental methods. When compared with segmented PU copolymers having predominately poly(dimethyl siloxane) soft segments, these siloxane–carbonate soft segment copolymers exhibit enhanced intersegment mixing, and consequently relatively low mechanical modulus. With relatively low modulus and siloxane units in the soft phase, the siloxane–carbonate PUs have potential for use in cardiac and orthopedic biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Novel aliphatic poly(ester‐carbonate) with pendant allyl ester groups and its folic acid functionalization

A series of novel poly(ester‐carbonate)s bearing pendant allyl ester groups P(LA‐co‐MAC)s were prepared by ring‐opening copolymerization of L ‐lactide (LA) and 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one (MAC) with diethyl zinc (ZnEt₂) as initiator. NMR analysis investigated the microstructure of the copolymer. DSC results indicated that the copolymers displayed a single glass‐transition temperature (T_g), which was indicative of a random copolymer, and the T_g decreased with increasing carbonate content in the copolymer. Then NHS‐activated folic acid (FA) first reacted with 2‐aminoethanethiol to yield FA‐SH; grafting FA‐SH to P(LA‐co‐MAC) in the presence of TEA produced P(LA‐co‐MAC)/FA. The structure of P(LA‐co‐MAC)/FA and its precursor were confirmed by ¹H NMR and XPS analysis. Cell experiments showed that FA‐grafted P(LA‐co‐MAC) had improved adhesion and proliferation behavior of vero cells on the polymer films. Therefore, the novel FA‐grafted block copolymer is expected to find application in drug delivery or tissue engineering. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1852–1861, 2008     

Aliphatic poly(ester‐carbonate)s bearing amino groups and its RGD peptide grafting

This article deals with (1) synthesis of novel cyclic carbonate monomer (2‐oxo [1,3]dioxan‐5‐yl)carbamic acid benzyl ester (CAB) containing protected amino groups; (2) ring‐opening copolymerization of the cyclic monomer with L ‐lactide (LA) to provide novel degradable poly(ester‐carbonate)s with functional groups; (3) removal of the protective benzyloxycarbonyl (Cbz) groups by catalytic hydrogenation to afford the corresponding poly(ester‐co‐carbonate)s with free amino groups; (4) grafting of oligopeptide Gly‐Arg‐Gly‐Asp‐Ser‐Tyr (GRGDSY, abbreviated as RGD) onto the copolymer pendant amino groups in the presence of 1,1′‐carbonyldiimidazole (CDI). The structures of P(LA‐co‐CA/RGD) and its precursor were confirmed by ¹H NMR analysis. Cell experiments showed that P(LA‐co‐CA/RGD) had improved adhesion and proliferation behavior. Therefore, the novel RGD‐grafted block copolymer is promising for cell or tissue engineering applications. © Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7022–7032, 2008     

Electrospun poly(aniline‐co‐ethyl 3‐aminobenzoate)/poly(lactic acid) nanofibers and their potential in biomedical applications

Poly(aniline‐co‐ethyl 3‐aminobenzoate) (3EABPANI) copolymer was blended with poly(lactic acid) (PLA) and co‐electrospun into nanofibers to investigate its potential in biomedical applications. The relationship between electrospinning parameters and fiber diameter has been investigated. The mechanical and electrical properties of electrospun 3EABPANI‐PLA nanofibers were also evaluated. To assess cell morphology and biocompatibility, nanofibrous mats of pure PLA and 3EABPANI‐PLA were deposited on glass substrates and the proliferation of COS‐1 fibroblast cells on the nanofibrous polymer surfaces determined. The nanofibrous 3EABPANI‐PLA blends were easily fabricated by electrospinning and gave enhanced mammalian cell growth, antioxidant and antimicrobial capabilities, and electrical conductivity. These results suggest that 3EABPANI‐PLA nanofibrous blends might provide a novel bioactive conductive material for biomedical applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

Synthesis and properties of cationic ionomers from poly(ester‐urethane)s based on polylactide

l ‐Lactide (l ‐LA) was polymerized in the presence of N‐methyldiethanolamine as an initiator and Sn(Oct)₂ as a catalyst to give hydroxy‐telechelic poly(l ‐lactide) (PLLA‐diol) bearing a tertiary amine group at the center of the polymer chain. Successive chain extension of the PLLA‐diol with hexamethylene diisocyanate afforded PLLA‐based poly(ester‐urethane)s (PEU) with equally spaced tertiary amine groups. Treatment of the PEU with iodomethane converted tertiary amine groups to quaternary ammonium groups to give cationic ionomers (PEU‐MeI). The thermal, mechanical, hydrophilic, and biodegradation properties of the obtained polymers were investigated. The thermal properties of the PEUs and the PEU‐MeIs were similar each other. The PEU‐MeIs exhibited higher tensile modulus than those of the starting PEUs. The contact angles of water on the PEU‐MeIs were lower than those of the PEUs with similar NMDA content indicating their higher hydrophilicity. In compost degradation tests, the PEU‐MeIs showed slower degradation than those of the PEUs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4423–4428     

Synthesis and characterization of star oligo/poly(2,2‐dimethyltrimethylene carbonate)s containing cholic acid moieties

Star oligo/poly(2,2‐dimethyltrimethylene carbonate)s containing cholic acid moieties were synthesized through the ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate (DTC) initiated by cholic acid with hydroxyl groups. Through the control of the feed ratio of the initiator cholic acid to the monomer DTC, a series of star oligomers/polymers with different molecular weights were obtained. The star oligomers/polymers were characterized with Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, combined size exclusion chromatography/multi‐angle laser light scattering analysis, wide‐angle X‐ray scattering, polarizing light microscopy, and differential scanning calorimetry. Compared with linear poly(2,2‐dimethyltrimethylene carbonate), these star oligo/poly(2,2‐dimethyltrimethylene carbonate)s had much faster hydrolytic degradation rates. With one of the star oligomers/polymers, a microsphere drug‐delivery system of a submicrometer size was fabricated with a very convenient ultrasonic dispersion method that did not involve toxic organic solvents. The in vitro drug release was studied. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6688‐6696, 2006     

Polyesters,polycarbonate, and polyurethanes from a novel monomer: α,α,α′,α′-tetramethyl-1,4-tetrafluorobenzenedimethanol

The novel diol monomer, α,α,α′,α′-tetramethyl-1,4-tetrafluorobenzenedimethanol, has been synthesized by a convenient route which involves the addition of acetone to 1,4-dilithiotetrafluorobenzene and can be purified by washing with hexanes. It does not directly undergo condensation polymerizations with diacid chlorides. Its disodium salt, prepared by its reaction with sodium hydride, similarly fails to undergo such polymerizations readily. However, the dilithium salt, prepared in situ by the reaction of the title diol with 2 equiv of n-butyllithium in tetrahydrofuran, is suitable for the preparation of various classes of condensation polymers. Four polyesters and one polycarbonate derived from the reactions of the dilithium salt of the diol with adipoly dichloride, sebacoyl dichloride, isophthaloyl dichloride, terephthaloyl dichloride, and phosgene and two polyurethanes derived from its reactions with tolylene-2,4-diisocyanate and methylene-di-1,4-phenyl diisocyanate were prepared. Each was fully characterized by GPC, NMR, IR, and UV-visible spectroscopies, and the results of these studies are reported herein. © 1993 John Wiley & Sons, Inc.     

Characterization of polysuccinate and hydroxyapatite‐based nanocomposites containing poly(ester‐anhydride) microspheres

Repair and regeneration of bone defects with particular shape may be enhanced by in situ forming biomaterials which can be used in minimal invasive surgery. This study is aimed to prepare novel in situ forming biodegradable nanocomposites based on poly(3‐allyloxy‐1,2‐propylene) succinate (PSAGE) and nanosized hydroxyapatite (HA). These nanocomposite materials contain poly(ester‐anhydride) (PEA) microspheres embedded in a polyester matrix prepared by crosslinking PSAGE with oligo(1,2‐propylene maleate) and methacrylic monomers. Methyl methacrylate and one of hydrophilic oligo(ethylene glycol) methacrylates with different functionality and various length of oligooxyethylene chains were used as polymerizable diluents. Incorporation of microspheres which degrade faster than crosslinked polyester matrices enables formation of porous structure in situ. The obtained materials are liquid before curing and harden in several minutes with moderate exothermic effect. The effect of the composition of nanocomposite materials on selected properties, such as water sorption, mechanical strength, porosity and hydrolytic degradation process, was investigated. Rheological behavior and injectability of liquid formulations were studied. Analysis by energy dispersive spectroscopy confirmed the presence of characteristic features of HA in the nanocomposite materials. The morphology of the cured nanocomposites subjected to hydrolytic degradation was evaluated by scanning electron microscopy. The MTS cytotoxicity assay was carried out for extracts from crosslinked materials using hFOB1.19 cells. It was found that the extracts exhibit a dose‐dependent cytotoxic response. Copyright © 2014 John Wiley & Sons, Ltd.     

New aliphatic poly(ester‐carbonates) based on 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one

The synthesis, characterization, and ring‐opening polymerization of a new cyclic carbonate monomer containing an allyl ester moiety, 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one (MAC), was performed for the first time. MAC was synthesized in five steps in good yield beginning from the starting material, 2,2‐bis(hydroxymethyl)propionic acid. Subsequent polymerization and copolymerizations of the new cyclic carbonate with rac‐lactide (rac‐LA) and ?‐caprolactone (CL) were attempted. Rac‐LA copolymerized well with MAC, but CL copolymerizations produced insoluble products. Oligomeric macroinitiators of MAC and rac‐LA were synthesized from stannous ethoxide, and both macroinitiators were used for the controlled ring‐opening polymerization of rac‐LA. The polymerization kinetics were examined by monitoring the disappearance of the characteristic C? O ring stretch of the monomer at 1240 cm^?1 with real‐time in situ Fourier transform infrared spectroscopy. Postpolymerization oxidation reactions were conducted to epoxidize the unsaturated bonds of the MAC‐functionalized polymers. Epoxide‐containing polymers may allow further organic transformations with various nucleophiles, such as amines, alcohols, and carboxylic acids. NMR was used for microstructure identification of the polymers, and size exclusion chromatography and differential scanning calorimetry were used to characterize the new functionalized poly(ester‐carbonates). © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1978–1991, 2003     

Synthesis and structural analysis of functionalized poly (ϵ‐caprolactone)‐based three‐arm star polymers

Hydroxyl‐functionalized three‐arm poly(?‐caprolactone)s (PGCL‐OHs) were synthesized by the ring‐opening polymerization of ?‐caprolactone in the presence of glycerol (as the core) and stannous octoate. The effect of the feed ratio of ?‐caprolactone to glycerol on the ring‐opening polymerization was studied. These three‐arm PGCL‐OHs were then converted into double‐bond‐functionalized three‐arm poly(?‐caprolactone)s (PGCL‐Mas) by the reaction of PGCL‐OH with maleic anhydride in the melt at 130 °C. The quantitative conversion of hydroxyl functionality was achieved at a low molecular weight. The resulting PGCL‐OH and PGCL‐Ma were characterized with gel permeation chromatography, Fourier transform infrared, ¹H NMR, ¹³C NMR, and differential scanning calorimetry. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1127–1141, 2002     

Syntheses,characterization, and properties of multiblock copolymers consisting of polyisobutylene and poly(L‐lactide) segments

The syntheses of {‐poly(L ‐lactide) (PLLA)‐b‐polyisobutylene (PIB)‐}_n multiblock copolymers were accomplished for the first time by chain extension of PLLA‐b‐PIB‐b‐PLLA triblock copolymers. Well‐defined PLLA‐b‐PIB‐b‐PLLA triblock copolymers with predictable M_ns, low PDIs (1.10–1.18) and excellent blocking efficiencies were prepared by anionic ring‐opening polymerizations of L ‐lactide initiated with hydroxyallyl telechelic PIB (HO‐Allyl‐PIB‐Allyl‐OH) in toluene at 110 °C. The triblock copolymers were successfully chain extended with 4,4′‐methylenebis(phenylisocyanate) (MDI) to obtain the multiblock copolymers with good gravimetric yields of ～86 to 96%. The chain‐extended polymers were soluble in a range of common organic solvents. The block copolymers showed two glass transition temperatures in differential scanning calorimetric analysis for the PIB and PLLA blocks indicating microphase separation, which was supported by atomic force microscopy images. The as‐synthesized compression molded multiblock copolymers exhibited tensile strengths in the range of 8–24 MPa with elongations at break in the range of 2.5–400%. The static and dynamic mechanical properties showed a strong dependence on the relative PLLA content in the copolymer. The dynamic mechanical analysis also indicated microphase separation at higher PLLA compositions. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3490–3505, 2009     

Hydrophilic–hydrophobic AB diblock copolymers containing poly(trimethylene carbonate) and poly(ethylene oxide) blocks

AB‐type block copolymers with poly(trimethylene carbonate) [poly(TMC); A] and poly(ethylene oxide) [PEO; B; number‐average molecular weight (M_n) = 5000] blocks [poly(TMC)‐b‐PEO] were synthesized via the ring‐opening polymerization of trimethylene carbonate (TMC) in the presence of monohydroxy PEO with stannous octoate as a catalyst. M_n of the resulting copolymers increased with increasing TMC content in the feed at a constant molar ratio of the monomer to the catalyst (monomer/catalyst = 125). The thermal properties of the AB diblock copolymers were investigated with differential scanning calorimetry. The melting temperature of the PEO blocks was lower than that of the homopolymer, and the crystallinity of the PEO block decreased as the length of the poly(TMC) blocks increased. The glass‐transition temperature of the poly(TMC) blocks was dependent on the diblock copolymer composition upon first heating. The static contact angle decreased sharply with increasing PEO content in the diblock copolymers. Compared with poly(TMC), poly(TMC)‐b‐PEO had a higher Young's modulus and lower elongation at break. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4819–4827, 2005     

Fully biodegradable polymeric micelles based on hydrophobic‐ and hydrophilic‐functionalized poly(lactide) block copolymers

Novel amphiphilic diblock copolymers from a combination of hydrophobic‐functional poly(lactides) (PLAs) with hydrophilic‐functional PLAs or poly(malic acid), respectively, toward fully biodegradable materials for medical applications, such as micellar drug delivery systems, are reported for the first time. The presented PLA‐based polymeric micelles are characterized by their small size below 100 nm, low critical micellar concentrations, good in vitro stabilities at room and body temperature, and efficient incorporation capability of hydrophobic compounds, particularly with regard to potential drug substances. Moreover, the advantage of being totally degradable with different rates at different pH values, as investigated in medical cancer treatment, is demonstrated. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3244–3254, 2010     

Thermal properties of poly(alkylene dicarboxylate)s derived from 1,12‐dodecanedioic acid and even aliphatic diols

A series of new aliphatic polyesters derived from 1,12‐dodecanedioic acid and different diols with an even number of methylene units have been studied to assess the effect of the chemical structure on the final thermal properties of the materials. The polyesters have high thermal stability and are fast crystallizing polymers, with crystallization rate similar to that of polyethylene (PE). This behavior is connected to the fact that long aliphatic chains assume conformational characteristics very similar to that of PE. However, the polyester prepared from ethanediol shows a peculiar behavior (for example, double melting peak, melting and crystallization temperatures, which do not fit the trend of those of the other samples and ringed spherulites) owing to a probable different conformation, deviating from the all‐trans planar typical of PE. In the isothermal crystallization studies, a bell‐shape trend has been found for the crystallization rate as a function of the number of ? (CH₂)? units in the diol. The high crystallization rate of the sample with long ? (CH₂)? sequences has been attributed to the high chain flexibility and, thus, high mobility in the molten state and ease of chain folding. By reducing the aliphatic sequence length, instead, implications of the structural characteristics of the samples are probably involved. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1053–1067, 2007     

Polymer cyclization inhibits thermal decomposition of carbon‐dioxide‐derived poly(propylene carbonate)s

Remarkable enhancement of CO₂‐derived poly(propylene carbonate) (PPC) against thermal decomposition was achieved by cyclization of linear PPCs. Thus, a CO₂‐derived linear vinyl‐telechelic PPC was synthesized by CO₂–propylene oxide alternating copolymerization initiated from H₂O followed by an end‐capping esterification with 4‐pentenoic acid. Cyclic PPC was synthesized by the end‐to‐end intramolecular reaction of the vinyl‐telechelic linear PPC by metathesis condensation. Comparison of the thermal decomposition temperature (T_d) with linear and cyclic PPCs confirms surprisingly enhanced T_ds of cyclic PPCs. The elimination of chain ends through cyclization is indeed valuable for enhancing T_d of CO₂‐derived PPCs and thus turn the spotlight on the materials design utilizing CO₂. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3336–3342     

Photoresponsive biodegradable poly(carbonate)s with pendent o‐nitrobenzyl ester

Photoresponsive amphiphilic diblock poly(carbonate)s mPEG₁₁₃‐b‐PMNC_n with pendent o‐nitrobenzyl ester group were synthesized through ring‐opening polymerization (ROP) using 1,8‐diazabi‐cyclo[5.4.0]undec‐7‐ene (DBU) as catalyst and monomethoxy poly(ethylene glycol) (mPEG) as macroinitiator. In aqueous solution, the copolymers can self‐assemble to spherical micelles with a PC core and a PEG shell. The critical micelle concentration (CMC), size, and morphology of the micelles were demonstrated by means of fluorescence spectroscopy, transmission electron microscopes (TEM), and dynamic light scattering (DLS). Under UV light irradiation, the amphiphilic copolymer micelles disassembled because of the photocleavage of o‐NB ester, and the light‐controlled release behaviors of payload Nile red were further proved. This study provides a convenient way to construct smart poly(carbonate)s nanocarriers for controlled drug release. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2770–2780     

Synthesis and characterization of novel biodegradable epoxy‐modified polyurethane elastomers

Biodegradable polyurethane elastomers with the potential for applications in medical implants were synthesized from the reaction of epoxy‐terminated polyurethane prepolymers (EUPs) with 1,6‐hexamethylenediamine as a curing agent. EUPs were themselves prepared from the reaction of glycidol and isocyanate‐terminated polyurethanes made from different molecular weights of poly(ε‐caprolactone) (CAPA) and 1,6‐hexamethylene diisocyanate. All materials were characterized by spectroscopic methods. The curing conditions were optimized by gel content measurements. The curing kinetic and kinetic parameters were determined from differential scanning calorimetry measurements. The effects of changing the crosslink density and crystallinity of elastomers via the alteration of the CAPA polyol molecular weight on the physical, mechanical, and degradation properties of the final elastomeric polymers were examined fully. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2985‐2996, 2005     

Effect of the composition ratio of copolymerized poly(carbonate) glycol on the microphase‐separated structures and mechanical properties of polyurethane elastomers

Randomly copolymerized poly(carbonate) glycols were employed as starting materials for the synthesis of polyurethane elastomers (PUEs). The poly(carbonate) glycols had hexamethylene (C₆) and tetramethylene (C₄) units between carbonate groups in various composition ratios (C₄/C₆ = 0/100, 50/50, 70/30, and 90/10), and the number‐average molecular weights of these poly(carbonate) glycols were 1000 and 2000. The PUEs were synthesized with these poly(carbonate) glycols, 4,4′‐diphenylmethane diisocyanate, and 1,4‐butanediol by a prepolymer method. Differential scanning calorimetry measurements revealed that the difference between the glass‐transition temperature of the soft segment in the PUEs and the glass‐transition temperature of the original glycol polymer decreased and the melting point of the hard‐segment domain increased with an increasing C₄ composition ratio. The microphase separation of the poly(carbonate) glycol‐based PUEs likely became stronger with an increasing C₄ composition ratio. Young's modulus of these PUEs increased with an increasing C₄ composition ratio. This was due to increases in the degree of microphase separation and stiffness of the soft segment with an increase in the C₄ composition ratio. The molecular weight of poly(carbonate) glycol also influenced the microphase‐separated structure and mechanical properties of the PUEs. The addition of different methylene chain units to poly(carbonate) glycol was quite effective in controlling the microphase‐separated structure and mechanical properties of the PUEs. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4448–4458, 2004     

Cinnamate‐functionalized poly(ester‐carbonate): Synthesis and its UV irradiation‐induced photo‐crosslinking

A functionalized cyclic carbonate monomer containing a cinnamate moiety, 5‐methyl‐5‐cinnamoyloxymethyl‐1,3‐dioxan‐2‐one (MC), was prepared for the first time with 1,1,1‐tri(hydroxymethyl) ethane as a starting material. Subsequent polymerization of the new cyclic carbonate and its copolymerization with L ‐lactide (LA) were successfully performed with diethyl zinc (ZnEt₂) as initiator/catalyst. NMR was used for microstructure identification of the obtained monomer and copolymers. Differential scanning calorimetry (DSC) was used to characterize the functionalized poly(ester‐carbonate). The results indicated that the copolymers displayed a single glass transition temperature (T_g) and the T_g decreased with increasing carbonate content and followed the Fox equation, indicative of a random microstructure of the copolymer. The photo‐crosslinking of the cinnamate‐carrying copolymer was also demonstrated. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 161–169, 2009