Biodegradable Poly(ester−urethane−amide)s Based on Poly(ε-caprolactone) and Diamide−Diol Chain Extenders with CrystallineHard Segments. Synthesis and CharacterizationJose E. Baez, Daniel Ramírez, Juan L. Valentín, and Angel Marcos-Fernandez*

Instituto de Ciencia y Tecnología de Polímeros (CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain

*S Supporting Information

ABSTRACT: Twenty seven poly(ester−urethane−amide)s (PEUAs) were synthesizedfrom the reaction of α,ω-telechelic poly(ε-caprolactone) diols, 1,6-hexamethylenediisocyanate, and three different diamide−diol chain extenders derived from ε-caprolactoneand three aliphatic diamines with increasing length (n = 2, 4, and 6). The hard segment(HS) was designed to be crystalline and to introduce amide groups, more susceptible tohydrolysis than urethane or urea groups. Crystallization of the HS was achieved even atvery low HS content, leading to a phase-separated material. Furthermore, HS crystallinityrecovered from the material homogeneous melt on cooling. Thermal degradation was wellabove HS melting point, allowing for melt processing of these materials. HS melting pointwas affected by HS content, poly(ε-caprolactone) diol length, and chain extender length.The length scale of the phase-separated morphology lied in between 11 and 13 nm up to∼60% HS content and decreased at higher HS content values. HS content was the mainparameter affecting the mechanical properties. The prepared PEUAs degraded hydrolyti-cally at very long times by surface erosion.

■ INTRODUCTIONPolyurethanes (PUs) are a versatile family of polymers thathave many industrial applications due to the possibility oftailoring their properties through their chemistry. Usually, PUsare built from the reaction of a macroglycol, a polyisocyanate,and a chain extender or cross-linker. When the finalmacromolecule is linear, the starting reagents are a difunctionalpolyol, a diisocyanate, and a difunctional chain extender, andthe resulting material is a multiblock segmented PU. The polyolconstitutes the so-called soft segments (SS), whereas thereaction of the diisocyanate and the chain extender constitutesthe so-called hard segments (HS), and depending on thethermodynamical incompatibility of the segments, they cansegregate in separated phases.1

PUs have been widely used in the biomedical area, mainly asbiostable materials.2 However, there is a continuous interestsince the 1990s in the development of biodegradable PUs forcontrolled release of drugs and tissue engineering applica-tions.3−7 Several reactants commonly used in the preparation ofpolyurethanes such as for example 4,4′-diisocyanatodiphenyl-methane (MDI) or 3,3′-dichloro-4,4′-diaminediphenylmethane(MOCA or MBOCA) degrade to toxic products and thereforehave to be excluded from the synthesis of biodegradable PUs. Itis therefore necessary to make a careful choice of the reactantsin order to obtain polymers with non toxic degradationproducts.Several possible reactants can be used as nontoxic polyols,

among them the poly(ε-caprolactone) (PCL) [−CO-(CH2)5O−]n, which is an aliphatic polyester with biodegradableand biocompatible properties. The methylenes in the main

chain of PCL impart a hydrophobic character to the polymer,leading to long degradation times in aqueous media.8,9 α,ω-Telechelic PCL diols (HO-PCL-OH) have been reported bymany authors as precursors in the synthesis of PUs.10−14

The aromatic diisocyanates generally used in the industrialpreparation of PUs degrade to toxic and even carcinogeniccompounds, and therefore other alternatives have been used forbiomedical applications such as L-lysine diisocyanate(LDI),7,12−17 1,6-diisocyanatohexane (HDI),7,11,17,18 and 1,4-diisocyanatobutane (BDI),19 which degrade to nontoxic or lowtoxic diamines.Several diols and diamines have been described as chain

extenders in the synthesis of biodegradable PUs: 1,4-butanediol,10,14,16,18 amino acid derivatives,7,17 ester diols,7,17

diurethane diols,21 and diurea diols22 are some examples. Whenreacted with the diisocyanate, the resulting urethane or ureagroups are very slowly degraded, and the introduction of morelabile functionalities such as an ester group7,17 facilitates thedegradation of the formed hard segment.We have previously prepared segmented nontoxic biode-

gradable PUs where the hard segment was a slowly degradingpolyurea composed of amino acids.13 Because of the asymmetryof the reactants, the hard segment did not form a separatedphase. Consequently, the mechanical properties of thesynthesized PUs were mainly dependent on the crystallinityof the PCL. As a step forward, we intend the synthesis of new

Received: May 16, 2012Revised: July 13, 2012

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nontoxic biodegradable PUs with a crystallizable hard segment.This hard segment will separate in a phase and will stronglyinfluence the mechanical properties of the final PUs. Inaddition, the introduction of more degradable sites in thechemical structure of the hard segment will increase itssusceptibility to degradation with respect to the usual hardsegments with solely urethane and/or urea groups.Some diamide−diol molecules [HO−R1−CONH−R2−

NHCO−R1−OH (where R1 and R2 are alkyl groups)] havebeen used in the synthesis of poly(ester−amide)s23−25 andpoly(amide−urethane)s,26 and they have also been proposed aschain extenders in segmented PUs.27 In the case of thepoly(amide−urethane)s, the final polymer was intended to beused as film or in textiles with resistance to light and solvents.In the case of the segmented PUs, the chain extenders werederived from γ-butyrolactone or ε-caprolactone and ethanol-amine or short aliphatic diamines, and the PUs were formulatedfor castable preparations with MDI-based prepolymers.In the work presented here, we have prepared three

diamide−diol chain extenders (DCE) based on ε-caprolactoneand ethane-, butane-, and hexanediamine. These chainextenders were reacted with three different aliphatic diisocya-natesLDI, HDI and BDIto obtain nine model polyur-ethane hard segments, and their crystallization ability wasevaluated. It must be noted that two of these models have beenalready described in ref 26. One diisocyanate, HDI, was chosento synthesize 27 new poly(ester−urethane−amide)s (PEUAs)based on PCL diol of three different molecular weights andwith different molar ratios of the reactants (or different hardsegment contents). None of the chain extenders used in thiswork was used in ref 27, and therefore they have not beenpreviously described as components of segmented PUs. ThePEUAs chemical structure, physical properties, and hydrolyticdegradation were characterized. The results were related to thelength of the PCL, the length of the chain extender, and thehard segment content on the PEUA.

■ EXPERIMENTAL SECTIONMaterials. ε-Caprolactone (CL), tin(II) 2-ethylhexanoate Sn-

(Oct)2, 1,6-diisocyanatohexane (HDI), 1,4-butane diisocyanate(BDI), 1,4-butylenediamine (BDA), and 1,6-hexamethylenediamine(HDA) were purchased from Aldrich Chemical Co. and used asreceived. L-Lysine diisocyanate (LDI, diisocyanate of the L-lysinemethyl ester or methyl 2,6-diisocyanatohexanoate) was kindly donatedby Kyowa Hakko Kogyo Co., Ltd., Japan, and used as received. α,ω-Telechelic poly(ε-caprolactone) diols (HOPCLOH) [Mn(NMR) =539, 1243, and 1923], purchased from Aldrich, were dried at 70 °Cand under vacuum for at least 5 h, and stored at ambient temperaturein a desiccator at vacuum until used. 1,2-Ethylenediamine (EDA),purchased from Aldrich, was blended with potassium hydroxide anddistilled before use. N,N-Dimethylacetamide, purchased from Scharlau,was vacuum-distilled from isocyanates (commercial polymeric MDI)in order to eliminate residual water and amines that would unbalancethe stoichiometry on the synthesis of the polymers. Distillationtemperature was kept below 60 °C to avoid solvent decomposition,and the distilled solvent was stored in an amber flask blanketed withnitrogen for not more than a week before use.Synthesis of Diamide−Diol Chain Extenders. Reaction was

carried out in a 100 mL round-bottom flask previously dried. In areaction example, 1,6-hexamethylenediamine (HDA) (3 g, 25.8 mmol)and ε-caprolactone (CL) (44.1 g, 387 mmol) were charged and heatedin a reflux system by stirring them in an oil bath a 70 °C for 2 h (CL/HDA molar ratio ≈15). After cooling the reaction mixture at roomtemperature a white precipitate was obtained. The precipitate was

filtered and washed with acetone and chloroform. The resultant whitesolid was then dried under vacuum.

N,N ′ -Hexamethylenebis (6-hydroxycaproamide) [HO-(CH2)5CONHCH2CH2CH2]2 (HDA-2CL). The product HDA-2CL(theoretical molecular weight = 344.3 g/mol) is a white powder.Yield: 66%. IR (cm−1): 3306 (ν, N−H), 3054 (νs‑trans, N−H), 2935(νas, CH2), 2860 (νs, CH2), 1630 (ν, CO), 1532 (δ, N−H), 1050(ν, C−OH), 728 (ρ, CH2), 685 (ω, N−H). 1H NMR data for HDA-2CL (400 MHz, DMSO-d6, ppm) (Figure 1): 7.72 (t, 1H, [NH]), 4.35

(s, 1H, [OH]), 3.35 (t, 2H, [CH2OH]), 2.99 (q, 2H, [HN−CH2]),2.02 (t, 2H, [CH2CO]), 1.46 (q, 2H, [CH2CH2OH]), 1.37 (q, 2H,[CH2CH2CO]), 1.37 (t, 2H, [HN−CH2−CH2]), 1.22 (q, 2H,[CH2(CH2)2CO]), 1.22 (t, 2H, [HN−(CH2)2−CH2]).

13C NMR(100 MHz, DMSO-d6, ppm): 171.9 (CO), 60.6 (CH2OH), 38.3(CH2NH), 35 .5 (CH2CO), 32 .3 (CH2CH2OH), 29 .1(CH2(CH2)2NH), 26.1 (CH2CH2NH), 25.3 (CH2(CH2)2CO), 25.2(CH2CH2CO). Tm (DSC) = 134 °C.

N , N ′ - B u t y l e n e b i s ( 6 - h y d r o x y c a p r o am i d e ) [ H O -(CH2)5CONHCH2CH2]2 (BDA-2CL). The product BDA-2CL (theoreticalmolecular weight = 316.2 g/mol) is a white powder. Yield: 55%. IR(cm−1): 3302 (ν, N−H), 3058 (νs‑trans, N−H), 2942 (νas, CH2), 2866(νs, CH2), 1630 (ν, CO), 1535 (δ, N−H), 1050 (ν, C−OH), 740(ρ, CH2), 689 (ω, N−H). 1H NMR data for BDA-2CL (400 MHz,DMSO-d6, ppm): 7.73 (t, 1H, [NH]), 4.34 (s, 1H, [OH]), 3.36 (t, 2H,[CH2OH]), 2.99 (t, 2H, [HN−CH2]), 2.02 (t, 2H, [CH2CO]), 1.46(q, 2H, [CH2CH2OH]), 1.35 (q, 2H, [CH2CH2CO]), 1.35 (t, 2H,[HN−CH2−CH2]), 1.23 (q, 2H, [CH2(CH2)2CO]).

13C NMR (100MHz, DMSO-d6, ppm): 172.0 (CO), 60.6 (CH2OH), 38.1(CH2NH), 35.5 (CH2CO), 32.3 (CH2CH2OH), 26.7 (CH2CH2NH),25.3 (CH2(CH2)2CO), 25.2 (CH2CH2CO). Tm (DSC) = 140 °C.

N,N′-Ethylenebis(6-hydroxycaproamide) [HO(CH2)5CONHCH2]2(EDA-2CL). The product EDA-2CL (theoretical molecular weight =288.2 g/mol) is a white powder. Yield: 36%. IR (cm−1): 3297 (ν, N−H), 3083 (νs‑trans, N−H), 2939 (νas, CH2), 2858 (νs, CH2), 1637 (ν,CO), 1556 (δ, N−H), 1047 (ν, C−OH), 768 (ρ, CH2), 718 (ω,N−H). 1H NMR data for EDA-2CL (400 MHz, DMSO-d6, ppm):7.79 (t, 1H, [NH]), 4.34 (s, 1H, [OH]), 3.36 (t, 2H, [CH2OH]), 3.06(t, 4H, [HN−(CH2)2−NH]), 2.02 (t, 2H, [CH2CO]), 1.46 (q, 2H,[CH2CH2OH]), 1.38 (q, 2H, [CH2CH2CO]), 1.23 (q, 2H,[CH2(CH2)2CO]).

13C NMR (100 MHz, DMSO-d6, ppm): 172.5(CO), 60.7 (CH2OH), 38.4 (CH2NH), 35.6 (CH2CO), 32.3(CH2CH2OH), 25.3 (CH2(CH2)2CO), 25.2 (CH2CH2CO). Tm(DSC) = 156 °C.

Synthesis of Poly(urethane−amide) Hard Segment Models.Reaction was carried out in a 50 mL round-bottom flask previously

Figure 1. 1H NMR (400 MHz) spectrum for HDA-2CL diamide−diolchain extender in DMSO-d6. Oligomeric species of PCL are indicatedby an asterisk.

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dried. In a reaction example, HDA-2CL diamide−diol chain extender(0.500 g, 1.4 mmol), 1,6-diisocyanatohexane (HDI) (0.235 g, 1.4mmol), and 5.3 mL of dry N,N-dimethylacetamide (DMA) (20% w/v)as solvent were charged and heated in a reflux system with stirring at80 °C. After dissolution of the monomers, tin(II) 2-ethylhexanoate(12 mg, one drop) was added, and the reaction mixture was stirred forfurther 12 h at 80 °C. The crude reaction was poured over an excess ofcool water, and a white solid was precipitated, filtered, and dried undervacuum. Yield was quantitative.Poly(urethane−amide) (PUA1) Derived from EDA-2CL and HDI.

The product PUA1 is a white powder. IR (cm−1): 3304 (ν, N−H),3075 (νs‑trans, N−H), 2938 (νas, CH2), 2861 (νs, CH2), 1680 (ν, CO, urethane), 1638 (ν, CO, amide), 1534 (δ, N−H), 1262 (δ, C−N−H), 1052 (ν, C−O, urethane), 729 (ρ, CH2). Tm (DSC) = 205 °C.Poly(urethane−amide) (PUA2) Derived from BDA-2CL and HDI.

The product PUA2 is a light yellow powder. IR (cm−1): 3298 (ν, N−H), 3061 (νs‑trans, N−H), 2934 (νas, CH2), 2858 (νs, CH2), 1677 (ν,CO, urethane), 1632 (ν, CO, amide), 1534 (δ, N−H), 1260 (δ,C−N−H), 1050 (ν, C−O, urethane), 733 (ρ, CH2). Tm (DSC) = 188°C.Poly(urethane−amide) (PUA3) Derived from HDA-2CL and HDI.

The product PUA3 is a light yellow powder. IR (cm−1): 3305 (ν, N−H), 3061 (νs‑trans, N−H), 2932 (νas, CH2), 2856 (νs, CH2), 1675 (ν,CO, urethane), 1616 (ν, CO, amide), 1572 (δ, N−H), 1536 (δ,N−H), 1262 (δ, C−N−H), 1050 (ν, C−O, urethane), 732 (ρ, CH2).Tm (DSC) = 168 °C.Poly(urethane−amide) (PUA4) Derived from EDA-2CL and BDI.

The product PUA4 is a white powder. IR (cm−1): 3305 (ν, N−H),2941 (νas, CH2), 1681 (ν, CO, urethane), 1639 (ν, CO, amide),1537 (δ, N−H), 1281 (δ, C−N−H), 1048 (ν, C−O, urethane). Tm(DSC) = 213 °C.Poly(urethane−amide) (PUA5) Derived from BDA-2CL and BDI.

The product PUA5 is a white powder. IR (cm−1): 3302 (ν, N−H),2943 (νas, CH2), 1681 (ν, CO, urethane), 1636 (ν, CO, amide),1534 (δ, N−H), 1281 (δ, C−N−H), 1049 (ν, C−O, urethane). Tm(DSC) = 211 °C.Poly(urethane−amide) (PUA6) Derived from HDA-2CL and BDI.

The product PUA6 is a white powder. IR (cm−1): 3302 (ν, N−H),2934 (νas, CH2), 1682 (ν, CO, urethane), 1632 (ν, CO, amide),1532 (δ, N−H), 1044 (ν, C−O, urethane). Tm (DSC) = 192 °C.Poly(urethane−amide) (PUA7) Derived from EDA-2CL and LDI.

The product PUA7 is a light yellow powder. IR (cm−1): 3296 (ν, N−H), 2941 (νas, CH2), 1688 (ν, CO, urethane), 1640 (ν, CO,amide), 1538 (δ, N−H), 1048 (ν, C−O, urethane). Tm (DSC) = 125°C.Poly(urethane−amide) (PUA8) Derived from BDA-2CL and LDI.

The product PUA8 is an off-white powder. IR (cm−1): 3295 (ν, N−H), 2941 (νas, CH2), 1687 (ν, CO, urethane), 1633 (ν, CO,amide), 1537 (δ, N−H), 1048 (ν, C−O, urethane). Tm (DSC) = 115°C.Poly(urethane−amide) (PUA9) Derived from HDA-2CL and LDI.

The product PUA9 is a white powder. IR (cm−1): 3297 (ν, N−H),2934 (νas, CH2), 1689 (ν, CO, urethane), 1633 (ν, CO, amide),1536 (δ, N−H), 1049 (ν, C−O, urethane). Tm (DSC) = 97 °C.Synthesis of a Poly(ester−urethane−amide)s (PEUA). A

typical reaction was carried out in a 50 mL round-bottom flaskpreviously dried by using the prepolymer method. As an example, thereaction procedure for polymer PU-2H-26 will be described.First step [prepolymer]: α,ω-telechelic poly(ε-caprolactone) diol

(HOPCLOH, Mn(NMR) = 1243) (1.545 g, 1.243 mmol), 1,6-diisocyanatohexane (HDI) (0.313 g, 1.864 mmol), tin(II) 2-ethyl-hexanoate (24 mg, two drops), and 3.7 mL of dry N,N-dimethylacetamide (DMA) (50% w/v) as solvent were charged andheated in a reflux system with stirring at 80 °C for 3 h. Second step[chain extension]: after prepolymerization, diamide−diol chainextender (DCE) N,N′-hexamethylenebis(6-hydroxycaproamide)(HDA-2CL) (731 mg, 2.0595 mmol) and 3.2 mL of DMA (30% w/v final concentration) were added, and the reaction mixture was stirredfor a further 3 h at 80 °C and then left overnight at room temperature(HOPCLOH:HDI:HDA-2CL molar ratio = 1:1.5:0.5). A poly(ester−

urethane−amide) (PEUA) film was obtained by casting in a leveledglass within a fume cupboard. The cast solution was covered with aconical funnel to protect it from dust and to avoid an excessively fastsolvent evaporation and allowed to stand at 80 °C for 12−15 h. Afterthis time, the PEUA film was released and dried for further 12−24 h invacuum.

Three different molar ratios HOPCLOH:HDI:DCE (1:1.5:0.5,1:2.5:1.5, and 1:3.5:2.5) were used in this work for each one of thechain extenders (EDA-2CL, BDA-2CL, and HDA-2CL) and macro-diols HO-PCL-OH (Mn(NMR) = 539, 1243, and 1923). In Table S1(Supporting Information) all the synthesized polymers are detailed.The poly(ester−urethane−amide)s (PEUA)s were named PU-XY-ZZfollowing this code: PU refers to poly(ester−urethane−amide); Xrefers to the Mn(RMN) of poly(ε-caprolactone) diol (1 = 1923, 2 =1243, 3 = 539); Y refers to the chain extender type (E = EDA-2CL, B= BDA-2CL, H = HDA-2CL), and ZZ refers to the hard segmentcontent of the polymer (wt %), defined as [(weight HDI + weightchain extender)/total polymer weight]. Finally, by this method 27different PEUAs were synthesized.

Spectrometric data for PU-2B-42: IR (cm−1): 3312 (ν, N−H,amide), 2935 (νas, CH2), 2862 (νs, CH2), 1726 (ν, CO, ester), 1660(ν, CO, urethane), 1631 (ν, CO, amide), 1536 (δ, N−H, amide),1237 (δ, C−N−H), 1161 (δ, O−CO, ester), 732 (ρ, CH2).

1HNMR data (400 MHz, DMSO-d6, ppm): 7.72 (t, 1H, [NH], amide),7.15 (1H, [NH], urethane), 7.00 (1H, [NH], urethane), 5.70 (1H,[NH], urethane), 4.34 (t, 2H, [CH2OH]), 4.10 (2H, a, [O−CH2]),3.97 (t, 2H, g, [CH2−OCO]), 3.88 (t, 2H, D, [CH2−OCONH]), 3.59(2H, b, [OCH2CH2OCO]), 3.36 (t, 2H, [CH2OH]), 2.99 (t, 2H, J,[CH2NHCO]), 2.92 (2H, A, [CH2NHCOO]), 2.26 (t, 2H, c,[CH2COO]), 2.02 (t, 2H, I, [CH2CONH]), 1.52 (2H, d,E, f,[CH2]), 1.28 (2H, e,B,C,G,K, [CH2]), 1.22 (2H, F,L, [CH2]).

13CNMR (100 MHz,DMSO-d6, ppm): 172.7 (CO, ester), 171.9 (CO, amide), 156.2 (CO, urethane).

Methods. Solution 1H and 13C NMR spectra were recorded atroom temperature on a Varian Inova 400 (400 MHz 1H and 100 MHz13C). DMSO-d6 was used as solvent. Spectra were referenced to theresidual solvent [δ (ppm) 2.50 (1H) and 39.51 (13C)].

DSC was performed in a Mettler Toledo DSC822e instrument. Twoscans (25−210 and −90−210 °C) were performed by using a heatingrate of 10 °C/min and cooling (210 to −90 °C, 10 °C/min) theinstrument between runs under nitrogen purge. The melting points(Tm) are given as the maximum of the endothermic transition, and thedata reported are taken from the second scan unless otherwise statedin the text. The degree of crystallinity (xi) for the PCL soft segmentwas calculated from the endothermic peak area ΔHi by xi = ΔHi/ΔHi

0,where ΔHi

0 is the heat of fusion for perfect PCL crystals (135.3 J/g).28

Thermogravimetric analysis (TGA) was carried out in a TA Q500instrument. Samples weighing between 10 and 20 mg were scanned inHi-Resolution mode with an initial heating rate of 10 °C/min under aflux of nitrogen.

SAXS measurements were taken at beamline BM16 at the EuropeanSynchrotron Radiation Facility (Grenoble, France). Samples wereplaced in between aluminum foils within a Linkam hot stage andheated at 10 °C/min while the SAXS spectra were recorded.Calibration of temperature gave a difference of ∼7 °C between thetemperature reading at the hot stage display and the real temperatureat the sample.

FT-IR spectra of the polymer films were obtained with anattenuated total reflectance spectroscopy (ATR) accessory in aPerkin-Elmer Spectrum One FT-IR spectrometer.

Tensile properties were measured in a MTS Synergie 200 testingmachine equipped with a 100 N load cell. Type 3 dumbbell test pieces(according to ISO 37) were cut from the films. A crosshead speed of200 mm/min was used. Strain was measured from crossheadseparation and referred to 12 mm initial length. Five samples wereevaluated for each PEUA.

GPC measurements were determined using a PerkinElmer gelpermeation chromatograph (Series 200 LC pump) equipped with arefractive index detector (IR 200a). A set of ResiPore columns(Polymer Laboratories) conditioned at 70 °C were used to elute

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samples at the flow rate of 0.3 mL/min of HPLC-grade N,N-dimethylformamide (DMF) with LiBr (0.1 wt %). Poly(methylmethacrylate) standards (Polymer Laboratories) were used forcalibration.In vitro degradation of the polymers was evaluated by measuring the

weight change of the hydrated polymer film in a phosphate buffersolution at 37 °C without solution renovation. A certain amount offilm was put into a vial of 20 mL capacity, filled with buffer solution,closed, and deposited in an incubator at 37 °C. At selected timeintervals the films were extracted, blotted with tissue paper,immediately weighed, and returned to the vial. The water uptakepercentage was calculated as follows: weight change (%) = [(Wm −W0)/W0] × 100 where Wm is the weight of hydrated specimen and W0is the initial weight of the specimen. Polymers were tested in duplicate.Scanning electron microscopy (SEM) photographs were taken in a

Philips XL30 environmental scanning electron microscope at highvacuum operated at 25 kV.

■ RESULTS AND DISCUSSION

Synthesis of Diamide−Diol Chain Extenders (DCE). Inprevious works, we have prepared biodegradable nontoxicpolyurethanes based on an amino acid disocyanate, LDI, andamino acid chain extenders.13 Because of the asymmetry ofthese reactants, the hard segments of the final segmentedpolyurethanes were amorphous and mixed with soft segments.As a result, the main contribution to the mechanical propertiesof the resulting materials came from the crystallization of thesoft segments. In this work, we try to prepare new segmentedpolyurethanes with crystalline hard segments that will promotea phase-separated morphology. This morphology will influenceall the physical properties including the mechanical.Three diamide−diol chain extenders [HO(CH2)5CONH-

(CH2)nNHCO(CH2)5OH, where n = 2 (EDA-2CL), 4 (BDA-2CL), and 6 (HDA-2CL)] derived from ε-caprolactone (CL)and three different aliphatic diamines [HN2−(CH2)n−NH2, n =2, 4, 6] were synthesized by ring-opening of ε-CL (Scheme 1).The starting diamines were chosen because of their relativelylow toxicity, which makes them good candidates for thepreparation of biodegradable materials, and for their symmetricstructure, that will favor the crystallization of the correspondingsynthesized chain extenders. In addition, the introduction ofamide groups in the chain extender structure is expected tofacilitate the hydrolysis of the hard segments by acidic or basicconditions and by the assistance of enzymes respect to hardsegments bearing only urethane functional groups. Thesynthesis of the chain extenders was carried out in a greatexcess of ε-CL at moderate temperature without presence ofcatalyst in order to avoid the propagation reaction of the ε-CL.Chemical structures were corroborated by 1H NMR and FT-IR.For the case of HDA-2CL chain extender, 1H NMR spectrum isshown in Figure 1. Signals corresponding to amide group[CONH, f, δ 7.72], methylenes close to hydroxyl group[CH2OH, a, δ 3.35], and methylenes close to amide group[CH2NHCO, h, δ 2.99] were observed. A minimum amount of

PCL oligomers [CH2O, δ 3.97 and CH2CO, δ 2.26] (∼3%)was detected in all samples, marked by an asterisk in Figure 1.This result demonstrates that propagation was almostcompletely avoided with this synthetic procedure. The FT-IRspectrum confirmed the structure of the reaction products, andtwo bands related to the vibrations of amide group at 1630 (ν,CO, amide I) and 1532 cm−1 (δ, N−H amide II) weredetected.Diamide−diols were analyzed by DSC (Table 1, entries 1−

3), and the melting temperature (Tm) was found to be inversely

proportional to the number of methylenes between diamidegroups. This result was expected because the density of amidegroups increases when the chain extender length decreases. Themeasured melting points for diamide−diol were generallyhigher than values reported in the literature, but a higher purityof our monomers cannot be concluded because the measure-ment method was not detailed29,30 or was different fromours.24,27 Thus, Tm = 156−157 °C27 (similar to the valuemeasured by us), 143 °C,29 126 °C,24 and 116−117 °C30 havebeen reported for EDA-2CL; 140 °C30 (140 °C measured by

Scheme 1. Synthesis of Diamide−Diol (DCE) Chain Extenders

Table 1. Thermal Properties of Diamide−Diol ChainExtenders (DCE) and Model Hard Segment Poly(urethane−amide)s (PUA)s Obtained by DSC

run 1 run 2

no. sample compositionTm(°C)

ΔHm(J/g)

Tm(°C)

ΔHm(J/g)

1 chainextender

EDA-2CL 156 167.0

2 chainextender

BDA-2CL 140 156.4

3 chainextender

HDA-2CL 134 154.4

4 PUA1 EDA-2CL +HDI

205 91.1 192 73.6

5 PUA2 BDA-2CL +HDI

188 88.7 175 66.8

6 PUA3 HDA-2CL +HDI

168 84.1 136 6.1

7 PUA4 EDA-2CL +BDI

213 104.0 207 78.8

8 PUA5 BDA-2CL +BDI

211 101.8 208 79.5

9 PUA6 HDA-2CL +BDI

192 92.9 178 53.7

10 PUA7 EDA-2CL +LDI

125 44.2 113a 4.2

11 PUA8 BDA-2CL +LDI

115 41.0 110a 3.0

12 PUA9 HDA-2CL +LDI

97 53.2 −a −

aFor LDI-based poly(urethane−amide)s, a Tg is found in the secondrun with a value of 28, 25, and 22 °C for PUA7, PUA8, and PUA9,respectively.

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us), 95 °C,29 and 88 °C24 for BDA-2CL; and 135−136°C27(134 °C measured by us), 135 °C,29 129 °C,30 and 95 °C24

for HDA-2CL.Synthesis of Model Poly(urethane−amide)s (PUA)s

Hard Segments. In the synthesis of poly(ester−urethane−amide)s PEUAs, the hard segment is built up by the reaction ofthe diamide−diol chain extender (DCE) and a diisocyanate.Consequently, as part of a sequential study, poly(urethane−amide)s (PUA)s hard segment models were synthesized byreacting, in equimolar proportions, the diamide−diols speciespreviously obtained and several diisocyanates, namely HDI,BDI, and LDI. These diisocyanates were chosen because theirresulting hydrolysis products, L-lysine, 1,4-butanediamine, and1,6-hexanediamine, are nontoxic or have a relatively lowtoxicity, especially if compared to the commonly used aromaticdiisocyanates, most of them producing carcinogenic diaminesafter hydrolysis. LDI has an asymmetric structure, and thecrystallinity of the derived poly(urethane−amide)s wasexpected to be low. On the other hand, BDI and HDI aresymmetrical, and highly crystalline poly(urethane−amide)swere expected.The reaction proceeded with quantitative yields at 80 °C for

12 h. FT-IR spectra for all PUAs samples presentedcharacteristic stretching vibrations for carbonyl group (CO) of urethane and amide at 1675−1680 and 1616−1638cm−1, respectively. DSC results shown in Table 1 (entries 4−

12) demonstrated that model hard segments were crystalline.Melting temperatures for BDI- and HDI-based modelsprecipitated from solution (run 1) were high, slightly higherfor BDI based models where the density of urethane groups ishigher. Melting temperature for PUA1 was similar to the valuereported in the literature (192−204 °C), and for PUA3 it wasslightly lower to reported (178−187 °C).27 Surprisingly, LDI-based materials were also crystalline, although with meltingtemperatures much lower than for the other models. Afterrecrystallization (run 2), melting temperatures for BDI- andHDI-based models decreased, with a larger decrease for HDI-based models, although in all cases the melting temperature waswell above ambient temperature. The amount of crystallinitywas also reduced as seen in the melting enthalpy values, verystrongly for PUA3, based on HDI and HDA-2CL. Thisdecrease was expected because the ordering of the chains forcrystallization is more difficult in the melt than whenprecipitated from solution. For LDI-based models, the materialwas amorphous after cooling from the melt, and a clear Tg wasobtained at values around ambient temperature, with a slightdecrease on the value when the length of the diamine increased.After Tg was reached, for polymers PUA7 and PUA8, acrystallization exotherm appeared followed by a meltingendotherm with a low enthalpy value; thus, crystallization wasvery strongly reduced, and for polymer PUA9, crystallinity wascompletely lost.

Table 2. Composition, Solubility, and Number-Average Molecular Weight (Mn) for the Synthesized Poly(ester−urethane−amide)s (PEUA)s

PEUAaMn(NMR)

HOPCLOHbdiamide−diol chain extender

(DCE)cmolar ratio HOPCLOH:

HDI:DCEhard segment(wt %)d

solubility DMF(LiBr 0.1%)f Mn(GPC)

e Mw/Mne

PU-1E-17 1923 EDA-2CL 1:1.5:0.5 17 +g 34 100 1.67PU-1E-31 1923 EDA-2CL 1:2.5:1.5 31 +h 22 900 1.52PU-1E-41 1923 EDA-2CL 1:3.5:2.5 41 −h

PU-2E-24 1243 EDA-2CL 1:1.5:0.5 24 +g 49 600 2.11PU-2E-41 1243 EDA-2CL 1:2.5:1.5 41 +h 20 400 1.56PU-2E-52 1243 EDA-2CL 1:3.5:2.5 52 −h

PU-3E-43 539 EDA-2CL 1:1.5:0.5 43 −h

PU-3E-62 539 EDA-2CL 1:2.5:1.5 62 −h

PU-3E-71 539 EDA-2CL 1:3.5:2.5 71 −h

PU-1B-18 1923 BDA-2CL 1:1.5:0.5 18 +g 26 800 1.67PU-1B-32 1923 BDA-2CL 1:2.5:1.5 32 +h 20 800 1.52PU-1B-42 1923 BDA-2CL 1:3.5:2.5 42 −h

PU-2B-25 1243 BDA-2CL 1:1.5:0.5 25 +g 27 600 1.86PU-2B-42 1243 BDA-2CL 1:2.5:1.5 42 +h 15 500 1.50PU-2B-53 1243 BDA-2CL 1:3.5:2.5 53 −h

PU-3B-43 539 BDA-2CL 1:1.5:0.5 43 +h 18 900 1.68PU-3B-63 539 BDA-2CL 1:2.5:1.5 63 −h

PU-3B-72 539 BDA-2CL 1:3.5:2.5 72 −h

PU-1H-18 1923 HDA-2CL 1:1.5:0.5 18 +g 32 400 1.64PU-1H-33 1923 HDA-2CL 1:2.5:1.5 33 +h 20 100 1.54PU-1H-43 1923 HDA-2CL 1:3.5:2.5 43 −h

PU-2H-26 1243 HDA-2CL 1:1.5:0.5 26 +h 44 900 1.79PU-2H-43 1243 HDA-2CL 1:2.5:1.5 43 +h 14 600 1.44PU-2H-54 1243 HDA-2CL 1:3.5:2.5 54 −h

PU-3H-44 539 HDA-2CL 1:1.5:0.5 44 +h 32 700 1.70PU-3H-64 539 HDA-2CL 1:2.5:1.5 64 −h

PU-3H-73 539 HDA-2CL 1:3.5:2.5 73 −haPU-XY-ZZ where PU is poly(ester−urethane−amide), X is the Mn(RMN) of poly(ε-caprolactone) diol (1 = 1923, 2 = 1243, 3 = 539), Y is thechain extender type (E = EDA-2CL, B = BDA-2CL, H = HDA-2CL), and ZZ is the hard segment content (wt %). bObtained by 1H NMR. cEDA-2CL = [HO(CH2)5CONHCH2]2, BDA-2CL = [HO(CH2)5CONHCH2CH2]2, and HDA-2CL = [HO(CH2)5CONHCH2CH2CH2]2.

dHardsegment (%) = (weight of HDI + weight of chain extender)/total weight of monomers × 100. eDetermined by gel permeation chromatography(GPC). f(+) Soluble, (−) insoluble, and (±) partially soluble. gAt room temperature (rt). hAt room temperature after heating at 190 °C.

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There exists an evident relationship between meltingtemperature of the model polymers and the length of thechain extender. Melting temperature decreased when chainextender length increased. This is due to the decrease in thedensity of polar groups in the polymer. For BDI- and HDI-based models, there is an increase in Tm value respect to thediamide−diol precursors (entries1−3). This increase can beexplained by the stronger intermolecular hydrogen bonding ofthe urethane groups respect to the amide groups. However, forLDI-based models, the asymmetry of the LDI diisocyanateprobably results in low order crystals that melt at even lowertemperatures than the corresponding diamide−diol precursors.For the synthesis of the segmented poly(ester−urethane−

amide)s, LDI was rejected because of the low crystallinity foundin the models. It was expected that crystallinity was even lowerin the segmented poly(ester−urethane−amide)s, where thelength of the hard segment moiety would be reduced withrespect to the hard segment model homopolymers. In the caseof BDI and HDI diisocyanates, both produced hard segmentsmodels with relatively high crystallinity and high meltingtemperatures. They have been used in the preparation ofbiodegradable polyurethanes, but for the preparation of thesegmented poly(ester−urethane−amide)s in this work, HDIwas chosen because of its much lower cost, commercialavailability in large quantities, and lower volatility. HDI derivedhard segments have and additional advantage respect to theBDI derived hard segment models; that is, their lower meltingtemperature will reduce the processing temperature ifprocessed from the melt, reducing the possibility of thermaldegradation.Synthesis of Poly(ester−urethane−amide)s (PEUA)s.

Three molar ratios of the reactants PCL:HDI:DCE werechosen for the synthesis of the PEUAs: 1:1.5:0.5, 1:2.5:1.5, and1:3.5:2.5. It is accepted that, in general, for linear polyurethanesit is necessary a minimum molar ratio of 1:2:1 in order toachieve a phase-separated morphology. The three molar ratiostested in this study are below this ratio, above this ratio, andwell above this ratio, in order to check the thermodynamicalincompatibility of these new chain extenders.After casting from the reaction solution and drying, the

resulting polymeric films were very insoluble (Table S2). Onlya few polymers, with the lower PCL:HDI:DCE molar ratio,were soluble at room temperature in polar solvents (DMSO,DMF, or DMF with 0.1 wt % LiBr). Heating the polymers inDMF with 0.1 wt % LiBr at 190 °C dissolved the polymers with1:1.5:0.5 and 1:2.5:1.5 molar ratio, except for the polymer PU-3E-43. In this particular case, a gel was formed during reaction,probably due to cross-linking through allophanate reaction(reaction of isocyanate with urethane groups) or even N-acylurea reaction (reaction of isocyanate with amide groups).For polymers with the highest molar ratio, 1:3.5:2.5, only a fewdissolved but reprecipitated on cooling. For these series, also agel was formed for polymers PU-3E-71 and PU-3B-72 duringthe synthesis. It is therefore clear that lower solubility of thepolymers was obtained by using higher molar ratios (longerhard segments). For the polymers with the lower molar ratio,1:1.5:0.5, with a hard segment content in between 17 and 44 wt%, the polymers remained soluble on cooling. For theintermediate ratio, 1:2.5:1.5, hard segment content limitedtheir solubility; thus, up to 43% hard segment weight remainedsoluble on cooling, whereas at 62−64% hard segment weightthe polymers reprecipitated on cooling.

The measured molecular weights of the polymers that weresoluble at 70 °C (Table 2) are typical for these segmentedpolymers, with a relatively broad polydispersity index inbetween 1.5 and 2.1 and values for molecular weight (Mn) inbetween Mn = 15 000 and 50 000 g/mol.13 The only noticeabletrend is the decrease in molecular weight when the molar ratioincreases (hard segment content increases) for polymers withthe same chemical structure.

Characterization of Poly(ester−urethane−amide)s(PEUA)s. Nuclear Magnetic Resonance (NMR). In Figure 2,

the 1H NMR spectrum of poly(ester−urethane−amide) (PU-2H-26) derived from the reaction of HOPCLOH, HDI, andHDA-2CL (Table 2) is shown. The characteristics signals ofmethylenes close to ester [−CH2−O−(CO)−, δ 3.97],urethane [−CH2−NH−(CO)−O−, δ 2.92], and amide[−CH2−NH−(CO)−, δ 2.99] functional groups demon-strated that the HDA-2CL diamide−diol chain extender couldbe introduced in the main chain of the PEUA. The isocyanategroup was not detected, indicating its complete reaction. Therest of the peaks were assigned in base to references in thearea.12,13,31 Complementary, 13C NMR spectrum in Figure 3shows the peaks for the carbonyl zone for three differentsamples: (a) α,ω-telechelic poly(ε-caprolactone) diol HOP-CLOH [−(CO)−O−, δ 172.7], (b) HDA-2CL diamide−diol chain extender [−(CO)−NH−, δ 171.9], and (c)poly(ester−urethane−amide) PU-2H-26. For the latter, threedifferent signals corresponding to ester, amide, and urethane[−O−(CO)−NH, δ 156.2] groups were observed. Thisevidence corroborated the presence of the functional groupsattributed to PU-2H-26 and observed by 1H NMR (Figure 2).

Infrared Analysis. FT-IR spectroscopy resulted very usefulfor the characterization of the carbonyl groups present in thesynthesized PEUAs. The sequential assignation of carbonylsgroups with different environments is shown in Figure 4. In thecase of α,ω-telechelic poly(ε-caprolactone) diol (HOPCLOH)(Figure 4a) a single band of carbonyl stretching vibrations at1722 cm−1 corresponding to ester group [−(CO)−O−] wasobserved. On the other hand, HDA-2CL diamide−diol chainextender (Figure 4b) showed the characteristic bands of amideI from CO stretching vibration and amide II from N−Hbending with C−N stretching vibration at 1630 and 1532 cm−1,

Figure 2. 1H NMR (400 MHz) spectrum for poly(ester−urethane−amide) PU-2H-26 in DMSO-d6.

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respectively. A similar pattern was observed in the other twoEDA-2CL and BDA-2CL diamide−diol chain extenders. InFigure 4c, a model poly(urethane−amide) (PUA3, Table 1)derived from HDA-2CL and HDI is shown. Two pairs of bandscan be seen: (a) the first assigned to urethane group at 1675and 1572 cm−1 due to carbonyl CO stretching vibration andN−H bending with C−N stretching vibration, respectively, and(b) the second pair corresponding to amide I (1616 cm−1) andII (1536 cm−1) previously assigned for HDA-2CL. It isinteresting to note that in PUA3 the IR bands tended tobroaden, probably because of amide−urethane interactions byhydrogen bonding. Finally, PEUA PU-2H-26 derived fromHOPCLOH, HDI, and HDA-2CL showed bands previouslyattributed at ester, urethane, and amide groups (see Figure 4d).Additionally, in PU-2H-26, other important vibrations could bedetected in the spectrum, e.g., N−H stretching, CH2 asym-metrical stretching, and CH2 symmetrical stretching at 3312,2935, and 2862 cm−1, respectively. Similar signals were alsofound in all PEUAs samples.Thermogravimetric Analysis (TGA). It is known that

polyurethanes are thermally unstable at high temperature. Inthe thermogravimetric analysis (TGA) for all PEUAs samples,three steps in the curve (Figure 5 and Table 3) were observed.It has been reported that the first weight loss during thermal

degradation of segmented polyurethanes is due to thedegradation of the hard segment as a consequence of therelatively low thermal stability of the urethane groups whereasthe second weight loss has been associated with soft segmentdecomposition.32 Similar behavior has been found forsegmented poly(urethane−urea)s.13,33 In those cases, duringhard segment degradation, the parent diisocyanate and chainextender were released, and the weight percentage of the losswas roughly the weight percentage of diisocyanate plus chainextender in the feed. In our PEUAs, the first weight loss, Td1 at258−277 °C, did not correspond in weight to the hard segmentcontent of the polymers. In fact, the first weight loss was above

the soft segment content of the polymers and close to it forPEUAs with hard segment based on HDA-2CL (see Table 3).However, the degradation temperature of this step decreasedwhen the hard segment content increased, as seen in Figure 5and Table 3. It demonstrated the lower stability of the urethanebonds respect to the amide and ester groups present in thePEUAs structure. This behavior is not contradictory and is dueto the structure of the chain extender. When the temperature ofdegradation for urethane groups was reached, the diisocyanateunits were released, but not the chain extender diamide units,because they are less volatile than usual chain extenders, e.g.,

Figure 3. 13C NMR (100 MHz) spectra of the carbonyl zone: (a) α,ω-hydroxypoly(ε-caprolactone) diol (HOPCLOH, Mn(NMR) = 1923),(b) N,N′-hexamethylenebis(6-hydroxycaproylamide) (HDA-2CL),and (c) poly(ester−urethane−amide) PU-2H-26.

Figure 4. FT-IR spectra of the carbonyl zone: (a) α,ω telechelicpoly(ε-caprolactone) diol (HO-PCL-OH) (Mn(NMR) = 1243), (b)amide diol (HDA-2CL) chain extender, (c) poly(urethane−amide)derived from HDI and HDA-2CL, and (d) poly(ester−urethane−amide) (PEUA) derived from PCL:HDI:HDA-2CL (molar ratio1:1.5:0.5).

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butanediol. The release of the diisocyanate was followed by thedegradation of the polycaprolactone chains, giving all togetherthe first weight loss in the thermogravimetric curve. This is thereason why the weight change was higher than thepolycaprolactone content in the polymer. Following thisreasoning, the second weight change in these PEUAs, Td2,was assigned to the degradation of the chain extender enteringthe hard segment. This weight loss took place at 282−315 °C,in the range of degradation temperatures reported by Katayamaet al. for PUA1 and PUA3 (305 °C),27 supporting theassumption that it was related to the diamide−diol chainextender degradation. In addition, the weight change in thisstep increased with the increase in hard segment content(Figure 5), and for the PEUAs based on HDA-2CL itapproached the diamide−diol content in the polymer (Table3). For PEUAs based on BDA-2CL and EDA-2CL, the firstweight loss was much higher than the PCL content in thepolymer, and the second weight loss was much lower than thediamide−diol content in the polymer. It seems that for thesepolymers part of the chain extender was released with the PCLin the first weight loss. It could be probably due to the jointeffect of higher volatility because of the shorter chain of theextender and the higher onset of decomposition. From the datain Table 3 it can be deduced that the onset of degradation isslightly dependent on the chain extender length following thetrend HDA-2CL < BDA-2CL < EDA-2CL. The third weightloss, Td3 (418−438 °C), was related to the graphitization of theremaining organic structures, leaving a very small carbonaceousresidue at temperatures above 450 °C.For all the prepared PEUAs, the onset of degradation was

more than 50 °C above the melting point of the corresponding

hard segment models, leaving a wide window for meltprocessing of these polymers.

Differential Scanning Calorimetry (DSC). Both PCL andhards segments based on diamide−diol chain extenders (DCE)used in this work were semicrystalline. Therefore, a phasesegregation with two different crystalline phases could bepresent in the PEUAs. Table 4 shows the thermal propertiesfrom PEUAs obtained by DSC in the second heating step, andFigure 6 displays some curves for PEUAs with different hardsegment content (17−43%) derived from EDA-CL, as anexample.In all PEUA samples the hard segment (HS) was crystalline

with a melting temperature (Tm2) from 88 to 179 °C. It isimportant to note that even at a molar ratio 1:1.5:0.5, below theratio 1:2:1 generally accepted to be the minimum to achievephase separation, these PEUAs showed phase segregation. Itindicates the strong thermodynamical incompatibility of thehard segments derived from HDI and these diamide−diol chainextenders. Moreover, PEUAs derived from PCL withMn(NMR) = 1923 (PU-1Y-ZZ) and 1243 (PU-2Y-ZZ) showedcrystallizable soft segment (SS) (Tm1 = 7−40 °C), whereas forPEUAs synthesized from PCL with Mn(NMR) = 539 (PU-3Y-ZZ) the soft segment always remained amorphous.Tg values for the soft segment were in between −52 and −55

°C for PEUAs based on PCL of molecular weight 1923 and1243 g/mol independent of the HS content and the chainextender structure. This value was 5−8 °C higher than for PCLhomopolymer of similar molecular weight34 due to the mobilityrestrictions imposed by the HS on the chain ends. These resultsdemonstrate that soft segments are well separated in an almostpure phase or at least in a phase with a very limited hardsegment mixing. For PEUAs based on short PCL, 539 g/mol,Tg values were much higher, as expected, increasing when HScontent increased due to the increase in the rigidity of thepolymer, with very high HS contents (43−73%). The differencein Tg values for some polymers of this series (PU-3E-43, PU-3E-71, and PU-3B-72) with the same HS content and differentchain extender structure was unexpected. These differences inTg are due to the cross-link produced during polymerization, asmentioned in the discussion of the synthesis of these PEUAs.Thus, polymer PU-3E-43 had a Tg of −35 °C, 5 °C higher thanPU-3B-43 and PU-3H-44, whereas PU-3E-71 and PU-3B-72had a Tg of −16 and −18 °C, respectively, very high comparedto the Tg of −30 °C for PU-3H-73. In segmented poly-(urethane−urea)s previously synthesized by us, based on lysinediisocyanate and lysine or ornithine chain extender, where thePCL soft segment was partially segregated and partially mixedwith the hard segments, Tg values for polymers based on PCLof 539 g/mol were −6.9 and −10 °C, respectively.13 These

Figure 5. TGA of PEUAs derived from HDA-2CL with molar ratio1:1.5:0.5 and different PCL diol length.

Table 3. Thermal Degradation of Some Selected PEUAs Determined by TGA

PEUA chain extender Td1 (°C)a % weight loss Td2 (°C)

a % weight loss Td3 (°C)a

PU-1H-18 HDA-2CL 269 85 (82)b 289 9 (12)c 436PU-2H-26 HDA-2CL 265 75 (74)b 315 15 (17)c 432PU-3H-44 HDA-2CL 257 65 (56)b 303 23 (29)c 434PU-3H-64 HDA-2CL 268 38 (36)b 306 38 (43)c 432PU-3H-73 HDA-2CL 264 30 (27)b 302 47 (49)c 424PU-3B-72 BDA-2CL 272 36 (28)b 297 34 (47)c 418PU-3E-71 EDA-2CL 277 64 (29)b 297 17 (45)c 428

aCalculated from the value of the maximum in the derivative of weight. bCalculated from weight feed of PCL. cCalculated from weight feed ofdiamide−diol chain extender.

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values are much higher than for polymers PU-3E-62, PU-3B-63,and PU-3H-64 (−29 to −34 °C). This demonstrates that phaseseparation was enhanced in the PEUAs synthesized in thiswork, providing a much better defined phase-separatedmorphology.Melting point of the crystallized SS was always higher for

PEUAs with PCL of 1923 g/mol than for PEUAs based onPCL of 1243 g/mol. In general, also the SS crystallinity was

higher, as expected, with a decrease on the SS crystallinity whenHS content increased due to the increase on the rigidity of thematerial (see Figure 7). Even for the PEUAs with the lowestHS content, SS crystallinity was well below 65% and themelting point below 48−52 °C, the values reached for PCL

Table 4. Thermal Properties of the Synthesized Poly(ester−urethane−amide)s (PEUAs)

PEUA chain extender HS (wt %) Tg (°C)a Tm1 (°C)

a ΔH1 (J/g)a xi(PCL) (%)

b Tm2 (°C)a ΔH2 (J/g)

a ΔH2 (J/gHS)c

PU-1E-17 EDA-2CL 17 −53 40 25.4 22.6 88 4.1 24.1PU-1E-31 EDA-2CL 31 −53 28 17.6 18.8 160 19.0 61.3PU-1E-41 EDA-2CL 41 −54 22 13.9 17.4 176 23.2 56.6PU-2E-24 EDA-2CL 24 −53 20 13.4 13.0 134 12.6 52.5PU-2E-41 EDA-2CL 41 −52 15 7.1 8.9 161 24.9 60.7PU-2E-52 EDA-2CL 52 −54 12 3.9 6.0 168 30.0 57.7PU-3E-43 EDA-2CL 43 −35 136 19.3 44.9PU-3E-62 EDA-2CL 62 −29 167 38.1 61.4PU-3E-71 EDA-2CL 71 −16 179 33.0 46.5PU-1B-18 BDA-2CL 18 −53 40 26.4 23.8 89 6.0 33.3PU-1B-32 BDA-2CL 32 −54 31 17.9 19.4 153 19.8 61.9PU-1B-42 BDA-2CL 42 −55 29 13.6 17.3 162 26.7 63.6PU-2B-25 BDA-2CL 25 −53 26 16.4 16.2 124 11.6 46.4PU-2B-42 BDA-2CL 42 −53 16 6.7 8.5 147 23.7 56.4PU-2B-53 BDA-2CL 53 −53 13 3.7 5.8 167 34.2 64.5PU-3B-43 BDA-2CL 43 −40 128 22.6 52.6PU-3B-63 BDA-2CL 63 −31 150 38.3 60.8PU-3B-72 BDA-2CL 72 −18 152 36.0 50.0PU-1H-18 HDA-2CL 18 −53 38 23.8 21.4 92 2.5 13.9PU-1H-33 HDA-2CL 33 −54 25 13.4 14.5 122 14.4 43.6PU-1H-43 HDA-2CL 43 −55 22 11.1 14.4 154 31.9 74.2PU-2H-26 HDA-2CL 26 −53 22 15.1 15.1 125 12.6 48.5PU-2H-43 HDA-2CL 43 −54 9 4.1 5.3 124 20.2 47.0PU-2H-54 HDA-2CL 54 −53 7 3.0 4.8 157 41.2 76.3PU-3H-44 HDA-2CL 44 −40 109 19.6 44.5PU-3H-64 HDA-2CL 64 −34 130 34.0 53.1PU-3H-73 HDA-2CL 73 −30 138 42.0 57.5

aDetermined by DSC. bCalculated from ΔH1.cCalculated from ΔH2

Figure 6. DSC thermograms (second scan) of PEUAs derived fromEDA-2CL with molar ratio 1:1.5:0.5 and different PCL diol length.

Figure 7. Effect of HS content on the crystallinity of PCL for PEUAsbased on PCL of 1923 g/mol (open symbols) and 1243 g/mol (filledsymbols) and EDA-2CL (circles), BDA-2CL (squares), and HDA-2CL(triangles).

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homopolymers of different length.34 It is the consequence ofthe mobility restrictions at the PCL chain ends. From the graphit seems that SS crystallinity for PEUAs based on EDA-2CLand BDA-2CL reaches similar values at the same HS content,whereas PEUAs based on HDA-2CL tend to have slightly lowerSS crystallinity.In Figures 8 and 9, the values for HS melting point and HS

melting enthalpy (corrected for the HS content in the

polymers) are represented. For both sets of data, the scatteringwas very pronounced because it was difficult to properlyanalyze the endotherm peak assigned to HS melting. It usuallypresented several peaks (see Figure 6), and the listed value wascalculated from the peak maximum, but sometimes it did notcorrespond with the peak at the highest temperature (see

Figure 6, top curve). In addition, the HS melting peak wasbroad, and sometimes it slightly merged with the SS meltingpeak. These facts made difficult to calculate precisely the area ofthe peak. Nevertheless, some trends could be identified.For PEUAs with the same chemical structure (the same PCL

length and the same chain extender) HS melting point tendedto increase with the increase in HS content (increase in molarratio), for example PU-2B-25 < PU-2B-42 < PU-2B-53(continuous line in Figure 8). This is due to the increase inthe length of the hard segments. When the data were related tothe chemical structure of the PEUAs, other trends were found.Thus, for PEUAs with the same HS content and the same PCLlength, HS melting point decreased when the length of thechain extender increased, for example PU-1E-31 > PU-1B-32 >PU-1H-33 (dotted line in Figure 8). It is the same trend foundfor the HS models, and it is due to the lower concentration ofhydrogen bonds when the length of the chain extenderincreases. And for PEUAs with the same HS content and thesame chain extender (the series with ∼41% HS content), HSmelting point decreased when the length of the PCL decreased,for example, PU-1E-41 > PU-2E-41 > PU-3E-43 (broken line inFigure 8). This tendency was expected because the length ofthe hard segment should increase according to thestoichiometry.Compared to the HS models, the maximum melting point

reached in the synthesized PEUAs was always below themelting point of the HS models (see Table 1, run 1). This isrelated to the lower length of the HS in the PEUAs respect tothe HS models, although the difference decreased when thelength of the chain extender increased (for HDA-2CL chainextender the difference is lower).The analysis of the HS melting enthalpy (Figure 9) allowed

for the clear differentiation between the PEUAs with HScontent below 20%, with enthalpy values below 33 J/gHS andPEUAs with HS content above 20%, with high enthalpy valuesin between 44 and 76 J/gHS. The PEUAs with less than 20%hard segment and the PEUAs with the lowest HS melting pointhave the shortest length of the HS, and it is not enough for agood crystallization of the HS. No trend was found in the datarespect to any of the variables. For PEUAs based on EDA-2CLand BDA-2CL chain extenders, the maximum enthalpy reachedfor any polymer was below the melting enthalpy of the HSmodel (see Table 1), calculated either in the first run or in thesecond run. Nevertheless, the values were not far from themelting enthalpy of the HS model on the second run for thepolymers with the highest values of enthalpy. Surprisingly, thePEUAs based on HDA-2CL chain extender also exhibited highvalues of HS melting enthalpy, in contrast with the very lowvalue found in the second run for the corresponding HS model.We have not explanation for this behavior. If the reason was thelower mobility of the long chains in the HS model forrecrystallization from the melt respect to the shorter HS chainsin the PEUAs, the same should hold for EDA-2CL- and BDA-2CL-based HS models, but these two models were able torecrystallize from the melt in a very high extent.

Small-Angle X-ray Scattering (SAXS). A broad single peakwas observed in SAXS, as usually found in multiblockcopolymers such as these PEUAs. When the samples wereheated, the same behavior was always found, and the peakdisappeared when the HS melted, leaving a homogeneous melt.On cooling, a broad single peak appeared again, demonstratingthe reversibility of the phase-separated structure. The curves for

Figure 8. Effect of HS content on the HS melting point for thesynthesized PEUAs. Symbols as in Figure 7 and for the PEUAs basedon PCL of 539 g/mol: EDA-2CL (plus sign), BDA-2CL (diamond),and HDA-2CL (right-pointing triangle).

Figure 9. Effect of HS content on the HS melting enthalpy for thesynthesized PEUAs. Symbols as in Figure 8.

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PU-2H-43 are given in Figure S1 of the SupportingInformation.Two parameters were calculated over the scattering curve: (i)

the relative invariant, Q′, as the integral below the curve Iq2 vs qin between the detector limits, which is related to the extent ofthe phase separation, and (ii) the maximum on the scatteringcurve, qmax, related to the size scale of the separated phases,calculated also from the curve Iq2 vs q. It is well-known that forlamellar systems the length scale (L) of the phase separationcan be calculated directly from the curve Iq2 vs q, while forother morphologies a calculation of L from the I vs q curvegives more realistic results. For the current copolymers, we donot know if a lamellar morphology is present, but we are moreinterested on the changes with temperature than on theabsolute values, and the representation Iq2 vs q highlights themaximum and makes it easier to detect, especially when usingautomated macros for the processing of the high amount ofdata generated in a synchrotron experiment. Therefore, this willbe the criterion used here to get information on L.In Figure 10, the changes in Q′ and qmax during the heating

cycle are represented for polymer PU-2E-52. Initially, Q′

slightly increased with temperature due to a thermal effect, andwhen HS started to melt, Q′ decreased until complete melting.For some of the prepared PEUAs, with high soft segmentcontent and partially crystallized PCL, a small drop in Q′ wasseen when the PCL melted. The melting range for HS wasquite wide, as already observed by DSC. In the other hand, qmaxdid not vary much until complete melting approached and theSAXS peak disappeared.The long spacing (L) for the prepared PEUAs was measured

at 50 °C and listed in Table S3 of the Supporting Informationand represented in Figure 11. In general terms, it can be seenthat L value lies in between 11 and 13 nm up to a HS contentof 54%. From this value, L decreases when HS contentincreases. This change in the trend could be related to a changein the material morphology, from probably cocontinuous

morphology for the phases below 54% to a dispersed softsegment phase in a continuous HS matrix above 54%. No othertrends were evident from the data, except for the linear increaseon L with HS content for PEUAs based on the longer PCL diol(circles in Figure 11) in the HS interval studied here (17−43%).

Mechanical Properties. The mechanical properties of theprepared PEUAs are listed in Table 5. Polymers that formed agel during reaction, PU-3E-43, PU-3E-71, and PU-3B-72, andpolymer PU-3H-73, were too fragile, and their properties couldnot be measured. All polymers behaved as tough materials witha fast increase in stress at low strains followed, depending onthe polymer, by a slower increase in stress when strain increasesuntil failure (Figure S2 in the Supporting Information).Polymers with the lowest HS content, PU-1E-17, PU-1B-18,and PU-1H-18, presented a significant amount of crystallizedSS, and a clear yield point could be detected on the stress−strain curve.In Figure 12, the results for stress at break, strain at break,

and modulus are represented. The modulus increased and thestrain at break decreased when the HS content on the polymerincreased. The exception for these trends was the threepolymers with the lowest HS content. These polymers showeda slightly higher value for the modulus and smaller values forstrain at break than expected due to the crystalline PCL presentin these polymers. The trend for the rest of the polymers was asexpected for materials that increase their rigidity when the HScontent on the material increases. The values of stress at breakincreased steadily with the HS content for contents above 30%,but for lower HS contents, measured values were scattered. Thestress at break values span from 8 to 24 MPa, thus it can be saidthat these polymers have good mechanical properties.No other noticeable trend related to the length of the PCL

diol or to the structure of the chain extender was found in thedata. It can be concluded that HS content is the main

Figure 10. Changes in the relative invariant, Q′ (circles), and themaximum of the scattering curve, qmax (squares), during the heatingcycle for PEUA PU-2E-52.

Figure 11. Effect of HS content on the size scale (L) of the phase-separated morphology in the PEUAs based on PCL of 1923 g/mol(open circles), 1243 g/mol (filled squares), and 539 g/mol (opentriangles).

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parameter that governs the mechanical properties of thesePEUAs.Water Uptake and Degradation. Some samples of PEUAs

were immersed in a phosphate buffer solution at 37 °C, andtheir weight change was monitored at certain time intervals. InFigure 13 weight change (%) vs time (h) is plotted for eightdifferent PEUAs with different PCL chain length and hardsegment type.In general, all PEUAs derived from PCL with 1923 g/mol

molecular weight, e.g., PU-1B-18, PU-1B-32, and PU-1B-42,showed a negligible water absorption and swelling. The smallinitial loss at short times is probably due to the release ofoligomers, as found for polymers with hard segments based inamino acids13 and aliphatic segmented poly(ester−amide)sbased on poly(butylene adipate) and EDA + 2CL or BDA +2CL.35 The increase in HS content could increase thehydrophilic environment in the PEUA inducing polymerswelling. However, this fact was not observed because thecrystallinity of the HS acted as a barrier to water penetration.The rate of degradation after the initial loss was very slow, andalmost not weight change was produced after 2 months, thelongest time of measurements for these materials. Similarresults were obtained for aliphatic poly(ester−urethane)s basedon poly(butylene adipate) of 2000 g/mol molecular weight.36

These polyurethanes showed essentially no degradation afterimmersion in seawater for 160 days. It is known that PCL, usedin our PEUAs, hydrolyzes more slowly than poly(butyleneadipate), and therefore, slower degradation rates are expectedfor our PEUAs compared to the polyurethanes in this reference.Also, poly(ester−amide)s based on poly(butylene adipate) andEDA + 2CL or BDA + 2CL showed minimal weight losses of

maximum 3.4 wt % after immersion in phosphate buffersolution at 37 °C for 7 months.35 In this work, it wasdemonstrated that degradation took place preferentiallythrough ester bond cleavage.For PEUAs derived from PCL with 1243 g/mol molecular

weight, e.g. PU-2E-52, PU-2B-25, and PU-2B-42, the initial lossat short times was slightly higher than for the polymers basedon PCL with 1923 g/mol molecular weight. This was probablybecause of the shorter length of the hard segments (due to thestoichiometry) which lead to a higher fraction of low molecularweight species. After the initial step, the rate of degradation wassimilar, for these samples, with all the curves running practicallyparallel.A different behavior was found for PEUAs based on PCL

with 539 g/mol molecular weight. Swelling of these sampleswas clearly observed as an increase in weight at short times,followed by weight decay due to the extraction of lowmolecular weight species (see PU-3B-43 in Figure 13). Whenthe polymer was cross-linked, e.g. PU-3E-72 in Figure 13, thedecay at short times did not take place. In that samplemaximum swelling was reached at longer times followed by theslow decay produced by the hydrolytic degradation. Thisdifference in swelling behavior for samples based on theshortest PCL respect to samples based in longer PCL diols wasalready found in polymers with HS based on amino acids.13 Forthose polymers, the HS was mixed with the PCL soft segments,increasing the hydrophilicity of the material. As a consequence,the level of swelling was much higher than for the materialsdescribed in this work, for which the hard segment is phase-separated and crystalline. Although the swelling of polymersbased on PCL of 539 g/mol allows for the exposure of more

Table 5. Mechanical Properties of the Poly(ester−urethane−amide)s (PEUA)s

PEUA stress at yield (MPa) strain at yield (%) stress at break (MPa) strain at break (%) modulus (MPa)

PU-1E-17 5.2 ± 0.2 35 ± 4 12.3 ± 1.0 1010 ± 190 37 ± 3PU-1E-31 10.4 ± 1.3 370 ± 180 45 ± 3PU-1E-41 10.6 ± 0.9 190 ± 60 69 ± 5PU-2E-24 24 ± 4 1500 ± 200 36 ± 4PU-2E-41 10.0 ± 0.4 77 ± 17 94 ± 6PU-2E-52 11.4 ± 0.3 37 ± 9 129 ± 6PU-3E-43a

PU-3E-62 17 ± 4 80 ± 30 210 ± 30PU-3E-71a

PU-1B-18 6.1 ± 0.2 26 ± 4 9.7 ± 0.5 560 ± 90 65 ± 4PU-1B-32 10.0 ± 0.3 220 ± 30 73 ± 2PU-1B-42 10.7 ± 0.3 100 ± 20 127 ± 5PU-2B-25 10.5 ± 0.2 680 ± 70 30 ± 2PU-2B-42 9.9 ± 0.4 60 ± 10 89 ± 2PU-2B-53 13.3 ± 0.4 80 ± 30 148 ± 10PU-3B-43 9.7 ± 0.7 200 ± 70 81 ± 4PU-3B-63 15.3 ± 0.6 34 ± 5 165 ± 9PU-3B-72a

PU-1H-18 4.8 ± 0.2 46 ± 5 11.4 ± 0.7 880 ± 80 37 ± 2PU-1H-33 8.4 ± 0.2 174 ± 16 66 ± 3PU-1H-43 12 ± 4 110 ± 40 120 ± 6PU-2H-26 18.3 ± 1.2 1080 ± 70 20 ± 2PU-2H-43 10.2 ± 0.7 40 ± 4 104 ± 5PU-2H-54 15.2 ± 0.8 58 ± 15 230 ± 20PU-3H-44 13.5 ± 0.6 410 ± 40 90 ± 7PU-3H-64 15 ± 3 20 ± 7 210 ± 30PU-3H-73b

aGel was formed during reaction and properties could not be measured. bThe material was too fragile and properties could not be measured.

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material to hydrolysis, the rate of degradation was still veryslow, similar to the polymers based on longer PCL diols.Some PEUA samples were analyzed by SEM after 2 months

degradation in phosphate buffer at 37 °C. In Figure 14, threedifferent films derived from PU-2B-42, PU-3B-43, and PU-2H-43 are shown. Slight erosion on the surface of the film wasappreciated in these PEUA samples. Similar eroded surfaceswere seen for the rest of degraded PEUAs. The same superficialerosion pattern has been reported for other polyester-basedsegmented polymers.13,35

■ CONCLUSIONSThree diamide−diol chain extenders (DCE) derived fromlinear aliphatic diamines of different length (n = 2, 4, 6) and ε-

CL were prepared in high purity and used in the synthesis ofmodel poly(urethane−amide)s hard segments and newsegmented poly(ester−urethane−amide)s (PEUAs).Hard segments (HS) derived from these DCE and 1,6-

diisocyanatohexane (HDI) or 1,4-diisocyanatobutane werehighly crystalline with high melting points. HS derived fromL-lysine diisocyanate showed lower melting points with a muchlower crystallinity.PEUAs derived from PCL diols of molecular weight 539,

1243, or 1923 g/mol, HDI, and these three DCE presented aphase-separated morphology as proved by DSC and SAXS,even at a HS content as low as 17%.HS melting point in the PEUAs was lower than for the

corresponding HS models due to the shorter length of thesegments and increased when HS content increased. ForPEUAs of the same HS content and the same PCL length, HSmelting point decreased when the length of DCE increased dueto the lower concentration of hydrogen bonds. For PEUAs ofthe same HS content and the same DCE, HS melting pointdecreased when the length of the PCL decreased because thelength of the HS increased.Thermal degradation of these PEUAs was well above the

melting point of the HS, allowing for the melt processing ofthese materials. HS was thermally less stable than PCL softsegment, with a slight dependence on chain extender length.SAXS analysis demonstrated that at temperatures above the

melting of the HS the PEUAs became a homogeneous materialthat separated again in phases on cooling. The length scale ofthe phase-separated structure was fairly constant and decreasedwhen HS content was above 54%, probably due to a change inmorphology.Mechanical properties were good and were mainly affected

by the HS content.Water uptake was negligible for PEUAs with the longer PCL

diols and very small for PEUAs with the shortest PCL diol dueto the crystallinity of the hard segment. Degradation rate wasvery slow, and the degradation mechanism was proven to be bysurface erosion.The PEUAs described in this work are materials of good

processability and good mechanical properties with a potentialuse as biodegradable materials for applications requiring longdegradation times.

Figure 12.Mechanical properties of the synthesized PEUAs. From topto bottom: stress at break, strain at break, and modulus. Symbols as inFigure 11.

Figure 13. Weight change with time of immersion in phosphate buffersolution at 37 °C for hydrated PEUAs.

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■ ASSOCIATED CONTENT*S Supporting InformationSeries of the synthesized poly(ester−urethane−amide)s;solubility and long spacing of the polymers; real time SAXScurves and stress−strain curves. This material is available free ofcharge via the Internet at http://pubs.acs.org.

■ AUTHOR INFORMATIONCorresponding Author*E-mail amarcos@ictp.csic.es; Tel (+34) 912 587 555; Fax(+34) 915 644 853.

NotesThe authors declare no competing financial interest.

■ ACKNOWLEDGMENTSWe are indebted to the Ministry of Science and Innovation(MICINN) in Spain for their economic support of the work(MAT2008-00619 and MAT 2011-25513) and the access tothe synchrotron radiation source (experiments 16-2-87 and 16-2-94) in the European Synchrotron Radiation Facility (ESRF)in Grenoble, France. We are grateful to Dr. Ana Labrador andDr. Francois Fauth for their help at BM16 station at the ESRF.J.L.V. thanks Secretaria de Estado de Investigacion, Desarrollo eInnovacion (Spain) for his Ramon y Cajal contract. J.E.B. ismuch indebted to Consejo Nacional de Ciencia y Tecnologia(CONACYT, Mexico) for a postdoctoral fellowship (Exp.94112).

■ REFERENCES(1) Dieterich, D.; Grigat, E.; Hahn, W.; Hespe, H.; Schmelzer, H. G.In Polyurethane Handbook, 2nd ed.; Oertel, G., Ed.; Hanser: Munich,1993; Chapter 2, pp 11−53.(2) Szycher, M. In Scycher’s Handbook of Polyurethanes; CRC Press:Boca Raton, FL, 1999; Chapter 22, pp 1−12.(3) de Groot, J. H. Porous polymeric elastomers for repair andreplacement of the knee joint meniscus. Ph.D. Thesis, University ofGroningen, The Netherlands, 1995.(4) Skarja, G. A.; Woodhouse, K. A. J. Biomater. Sci., Polym. Ed. 1998,9, 271−295.(5) Flodin, P. (Artimplant, Sweden). U.S. Patent 6,220,441 B1, 2001.(6) Zhang, J.-Y.; Beckman, E. J.; Hu, J.; Yang, G.-G.; Agarwal, S.;Hollinger, J. O. Tissue Eng. 2002, 8, 771−785.(7) Caracciolo, P. C.; Buffa, F.; Abraham, G. A. J. Mater. Sci.: Mater.Med. 2009, 20, 145−155.

(8) Siparsky, G. L.; Voorhees, K. J.; Miao, F. J. Environ. Polym.Degrad. 1998, 6, 31−41.(9) Li, S. M.; Chen, X. H.; Groos, R. A.; McCarthy, S. P. J. Mater. Sci.:Mater. Med. 2000, 11, 227−233.(10) Bogdanov, B.; Toncheva, V.; Schacht, E.; Finelli, L.; Sarti, B.;Scandola, M. Polymer 1999, 40, 3171−3182.(11) Gorna, K.; Gogolewski, S. Polym. Degrad. Stab. 2002, 75, 113−122.(12) Baez, J. E.; Marcos-Fernandez, A.; Lebron-Aguilar, R.; Martínez-Richa, A. Polymer 2006, 47, 8420−8429.(13) Marcos-Fernandez, A.; Abraham, G. A.; Valentín, J. L.; SanRoman, J. Polymer 2006, 47, 785−798.(14) Ding, M.; Li, J.; Fu, X.; Zhou, J.; Tan, H.; Gu, Q.; Fu, Q.Biomacromolecules 2009, 10, 2857−2865.(15) Abraham, G. A.; Marcos-Fernandez, A.; San Roman, J. J. Biomed.Mater. Res. 2006, 76A, 729−736.(16) Hassan, M. K.; Mauritz, K. A.; Storey, R. F.; Wiggins, J. S. J.Polym. Sci., Polym. Chem. 2006, 44, 2990−3000.(17) Tatai, L.; Moore, T. G.; Adhikari, R.; Malherbe, F.; Jayasekara,R.; Griffiths, I.; Gunatillake, P. A. Biomaterials 2007, 28, 5407−5417.(18) Fernandez-dArlas, B.; Rueda, L.; de la Caba, K.; Mondragon, I.;Eceiza, A. Polym. Eng. Sci. 2008, 48, 519−529.(19) Heijkants, R. G. J. C. Polyurethane scaffolds as meniscusreconstruction materials. Ph.D. Thesis, University of Groningen, TheNetherlands, 2004.(20) Sarkar, D.; Yang, J.-C.; Lopina, S. T. J. Appl. Polym. Sci. 2008,108, 2345−2355.(21) Stapert, H. R.; Dijkstra, P. J.; Feijen, J. (University of Twente,The Netherlands). W.O. Patent 00454 A1, 1998.(22) Caracciolo, P. C.; de Queiroz, A. A. A.; Higa, O. Z.; Buffa, F.;Abraham, G. A. Acta Biomater. 2008, 4, 976−988.(23) Katayama, S.; Murakami, T.; Takahashi, Y.; Serita, H.; Obuchi,Y.; Ito, T. J. Appl. Polym. Sci. 1976, 20, 975−994.(24) Sudha, J. D. J. Polym. Sci., Polym. Chem. 2000, 38, 2469−2486.(25) Lips, P. A. M.; Broos, R.; van Heeringen, M. J. M.; Dijkstra, P. J.;Feijen, J. Polymer 2005, 46, 7834−7842.(26) Lin, I. S.; Gromelski Jr., S. J. Plastics Compounding 1985, March/April, 24−30.(27) Katayama, S.; Horikawa, H.; Ito, T.; Gomyo, N.; Obuchi, Y. J.Appl. Polym. Sci. 1971, 15, 775−796.(28) Crescenzi, V.; Manzini, G.; Calzolari, G.; Borri, C. Eur. Polym. J.1972, 8, 449−463.(29) Rose, J. K.; Schulz, H. W. (Union Carbide). U.S. Patent3,025,323, 1962.(30) Stapert, H. R.; Dijkstra, P. J.; Feijen, J. Macromol. Symp. 1998,130, 91−102.(31) Furukawa, M.; Mitsui, Y.; Fukumaru, T.; Kojio, K. Polymer2005, 46, 10817−10822.

Figure 14. SEM micrographs for PEUAs films surfaces degraded by hydrolysis in a phosphate buffer solution at 37 °C after 2 months: (a, b) PU-2B-25; (c, d) PU-3B-43; (e, f) PU-2H-43.

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(32) Petrovic, Z.; Zavargo, Z.; Flynn, J. H.; Macknight, W. J. J. Appl.Polym. Sci. 1994, 51, 1087−95.(33) Cervantes-Uc, J. M.; Moo Espinosa, J. I.; Cauich-Rodríguez, J.V.; Avila-Ortega, A.; Vazquez-Torres, H.; Marcos-Fernandez, A.; SanRoman, J. Polym. Degrad. Stab. 2009, 94, 1666−1677.(34) Baez, J. E.; Marcos-Fernandez, A.; Galindo-Iranzo, P. Polym.-Plast. Technol. Eng. 2011, 50 (8), 839−850.(35) Lips, P. A. M.; van Luyn, M. J. A.; Chiellini, F.; Brouwer, L. A.;Velthoen, I. W.; Dijkstra, P. J.; Feijen, J. J. Biomed. Mater. Res. 2006,76A, 699−710.(36) Moravek, S. J.; Hassan, M. K.; Drake, D. J.; Cooper, T. R.;Wiggins, J. S.; Mauritz, K. A.; Storey, R. F. J. Appl. Polym. Sci. 2010,115, 1873−1880.

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