Control of PLA Stereoisomers-Based Polyurethane Elastomers as

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Control of PLA Stereoisomers-Based Polyurethane Elastomers as Highly Efficient Shape Memory Materials Xiaoshan Fan, Beng H. Tan, Zibiao Li, and Xian Jun Loh ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.6b02652 • Publication Date (Web): 06 Dec 2016 Downloaded from http://pubs.acs.org on December 7, 2016

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ACS Sustainable Chemistry & Engineering

Control of PLA Stereoisomers-Based Polyurethane Elastomers as Highly Efficient Shape Memory Materials

Xiaoshan Fan1, Beng Hoon Tan2, Zibiao Li2*, Xian Jun Loh2,3

1

School of Chemistry and Chemical Engineering, Henan Normal University, China

2

Institute of Materials Research and Engineering (IMRE), A*STAR, 2 Fusionopolis

Way, Innovis, #08-03, 138634 Singapore 3

Department of Materials Science and Engineering, National University of Singapore,

9 Engineering Drive 1, Singapore 117576, Singapore

Correspondence: Z. Li ([email protected]) Tel: +65-63194767

1 ACS Paragon Plus Environment


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Abstract:

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Poly(lactic acid) (PLA) has received increasing attention in the

development of shape memory polymers (SMPs) due to its excellent physical properties and good biocompatibility. However, the intrinsically increased crystallinity of PLA at higher deformation ratios still remains as a significant challenge, which remarkably restricts the chain mobility and reduces shape recovery efficiency. Being different from other types of biodegradable polymers, the diverse isomeric forms of PLA have provided great opportunities for modulation of PLA towards a favourable property by incorporating different PLA stereoisomers in one macromolecular architecture. In this paper, we report a completely amorphous PLA poly(ester urethane) elastomer that exhibits excellent shape fixity (>99%) and shape recovery (>99%) in a time frame of seconds. By means of adjusting the stereoisomeric ratios and control over architecture, the resultant poly(PLLA/PDLLA urethane)s (PLDU) elastomers show a single glass transition temperature (Tg), as the only thermal event, in the range of 38 – 46 °C in a predictable manner. The elastic moduli of PLDU elastomers display a 100-fold loss during the sharp transition from glassy to rubbery state with temperature alternation across their corresponding Tg, indicating a successful manipulation of the thermo-mechanical properties by temperature as required in thermally induced SMPs. In addition, all samples display a typical elastomeric behavior with elongation at break (εb) greater than 400%. The effect of the stereoisomer content on the tensile modulus and elastic mechanical behavior were also systematically investigated. Together with the prominent degradation property, the new PLDU elastomers developed in this study show great potential for biomedical applications as shape memory implants. Keywords:

Biodegradable

Poly(lactic

acid),

Sustainability,

Amorphous, Shape Memory 2 ACS Paragon Plus Environment

Polyurethane,

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1. Introduction Shape memory polymers (SMPs) are a class of emerging smart materials that can be elastically deformed to programmed temporary shapes and recover their original shape upon application of an external stimulus, such as temperature, light, chemicals and magnetic field.1-3 Comparing with shape memory alloys, SMPs have larger deformation strain, low density and exhibit highly complex shape transformations in an easier process.4 These unique characteristics have made SMPs promising for a myriad of applications in actuators, sensors, microfluidic systems and biomedical applications.5 In general, SMPs consist of two components: cross-links determining the permanent shape and switching segments fixing the temporary shape below a critical transition temperature (Ttrans).6 Cross-linkage can be formed by either chemical bonds or physical interactions in SMPs. For thermal-responsive SMPs, the Ttrans is either glass transition temperature (Tg) or melting temperature (Tm), known as the Tgbased and Tm-dependent shape memory polymeric system, respectively.7 In thermalresponsive SMPs systems, the permanent shape is formed at the elastic state of the materials without external stress. It can be deformed to a desired temporary shape by external force at temperature above Ttrans, and this strained configuration can be fixed as the temperature cools below Ttrans. However, the permanent shape is retained during the cooling process of temporary shape fixing. When it is re-heated at above the Ttrans, the stored strain energy is released and SMPs return to the original permanent shape.8 Recently,

aliphatic

polyesters

such

as

poly(ε-caprolactone)

(PCL)9-11,

polyhydroxyalkanoate (PHA)12-15 and polylactic acid (PLA)16-20 are at the frontier of biodegradable polymer research due to their promising potential for biomedical applications, especially in the area of minimally invasive surgeries. Since the first



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demonstration of biodegradable SMPs in tissue engineering applications, many SMPs derived from biomass-based or biodegradable polymers have been developed and they are still in high demand.21-26 For example, Langer et al reported the synthesis of a series of biodegradable SMPs by coupling PCL and poly(p-dioxanone) (PPDO) using 1,6-diisocyanato-2,2,4-trimethylhexane.25 The shape-memory capability of these multiblock copolymers could enable the as-fabricated sutures to close an incision or open lumen at elevated temperature above Ttrans. PLA is a semicrystalline thermoplastic material exhibiting Tg and Tm in the ranges of 60 – 70 °C and 150 – 170 °C, respectively.27 Due to the excellent physical property and good biocompatibility, PLA has received increasing attention in the development of SMPs.28 The crystalline domains in PLA act as net points, whereas molecules in the amorphous phase works as switching segments with the Ttrans slightly higher than Tg. However, the permanent shape was only able to be recovered when the deformation ratio was low in the programming procedure. Higher deformation of PLA leads to an increased crystallinity, whereby the recovery ratio was remarkably reduced by the restricted chain mobility in the amorphous phase.29 In addition, the efficiency of the recovery process decreased significantly with increasing number of shape memory cycles. This is because some of the physical cross-links orientated from the crystalline phase of PLA were destroyed until steady state was reached.30 The slow crystallization rate and inadequate crystallization ability of PLA are also prone to cause cold crystallization at temperature above their Tg, which in turn prominently affects amorphous chains mobility in the shape recovery.31 To overcome these problems, various strategies have been explored to modulate the crystallinity and thermal mechanical behavior of PLA by controlling both architecture and compositions in shape memory applications, including plasticization, spinning into filament, and forming cross-linked networks of


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PLA homopolymers or copolymerizing PLA with other functional segments such as PCL, PGA and PEG etc.23, 29, 32, 33 Among these, completely amorphous PLA-based shape memory polymer networks are of particular interests due to their unique characteristics. The absence of crystalline phase in these networks results in high optical transparency, which is required for applications like replacement of ocular tissue.34,

35

Moreover, the materials show a more homogenous degradation feature

than crystallizable polymer networks since hydrolytic degradation occurs faster in amorphous regions than in crystalline ones. In contrast, the slow degradation of high crystalline oligomer particles at the end of process could lead to the formation of fibrous capsules in vivo.25, 36 The homogenous degradation behavior is advantageous for applications of this type of SMPs as implant materials. In addition, the reversible viscous flow in these covalently cross-linked systems could exhibit superior dimensional shape stability and retard the possible creep phenomena compared to the physically cross-linked PLA polymer networks.37 However, completely amorphous PLA polymers with thermally induced shape memory effect have not been extensively explored. Recently, Peter Ma et. al reported the synthesis of amorphous electroactive SMPs by copolymerization of star-shaped PLA and aniline trimer (AT).33 The initiator inositol was used in the ring opening polymerization (ROP) of six-arm PLA macromolecules and further acted as chemical net points as required for SMPs. The presence of AT in the chemically cross-linked networks greatly restricted the movement of the PLA chains, thus leading to the disappearance of crystal phase and high shape recovery ratio.33 In another example, multi-arm PLA and PLGA oligomers were coupled by different junction units to obtain completely amorphous copolyesterurethane networks.6 In this case, the functionalities of the crosslinks were defined by the branch points of the telechelic prepolymers, and the switching phases were formed



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by the amorphous segment chains. Macroscopic shape memory effect showed that that complex transformation from the temporary shape to the permanent shape took approximately 5 min at 70 °C. However, the Ttrans values of these resulting amorphous SMPs are based on the glass transition temperature Tg, which are between 55 – 60 °C. For biomedical applications the Tg values of the networks should be adjusted around body temperature while other thermal mechanical and shape memory properties of the SMPs are not compromised. Being different from other types of aliphatic polyesters, the constitutional unit of PLA is a chiral molecule containing two enantiomers known as L- and D- lactic acid. Polymerization of different forms of stereoisomeric monomers could therefore lead to a multitude of PLA chains and crystal structures.38 For instance, both isotactic poly(Llactic acid) (PLLA) and poly(D-lactic acid) (PDLA) are highly crystalline polymers, while the atactic poly(D,L-lactic acid) (PDLLA) is a completely amorphous polymer.39,

40

The polymorphism of PLA could allow one to modulate PLA

crystallinity simply by copolymerizing different PLA stereoisomers and adjusting their compositional ratios towards a favourable property for specific application.41 In this contribution, a series of completely amorphous PLA stereoisomers based poly(ester urethane) elastomers were synthesized by coupling PLLA-diol and PDLLA-diol oligomers using hexamethylene diisocyanate (HMDI). The secondary reaction between urethane and excess amount of isocyanate, which results in allophanate linkages were utilized to create a partially cross-linked architecture to facilitate shape memory behavior. By means of adjusting the stereoisomers contents in the materials, the resultant poly(PLLA/PDLLA urethane)s (PLDU) elastomers with transition temperature in the range of 38 – 46 °C could be obtained, which is significantly lower than the previously reported amorphous PLA networks (55 – 60 6 ACS Paragon Plus Environment

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°C). The effect of the macrodiols content on the tensile modulus and elastic mechanical behavior were also symmetrically investigated. The ductile PLDU elastomers demonstrated one-way shape memory effect with excellent shape fixing and recovery capabilities. Together with the prominent degradation property, PLDU elastomers show great potential for application in intelligent medical devices.

2. Experimental Section 2.1. Materials Dibutyltindilaurate (DBTL) (95%), stannous octoate [Sn(Oct)2] (95%), 1,6hexamethylene diisocyanate (HMDI) (98%), 1,4-Butanediol (99%), hexane, methanol (anhydrous, 99.8%), 1,2-dichloroethane (DCE) (99.8%), Butylamine (99.5%), Dichloromethane (DCM), Bromophenol Blue, and anhydrous toluene (99.8%) were purchased from Sigma-Aldrich. 1,2-Dichloroethane and 1,4-butanediol were distilled over CaH2 before use. L-Lactide (L-LA) and meso-lactide (DL-LA) were purchased from Purac Biochem and used as received.

2.2. Synthesis of PLLA and PDLLA Macrodiols by Ring Opening Polymerization (ROP) PLLA-diol and PDLLA-diol were synthesized through ring opening polymerization (ROP) of respective L- and meso-lactide using 1,4-butandiol as initiator and Sn(Oct)2 as catalyst (Scheme 1).17, 20 Typically, 0.9 g of 1,4-butandiol, 25 g of lactide monomer and 160 µl of Sn(Oct)2 were introduced into a 250 mL round bottom flask in a glovebox. 100 mL of anhydrous toluene was then added to the reactants under



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nitrogen atmosphere, and the mixture was stirred at 130 °C for 24 h under reflux. Purified products were obtained by precipitation of the reaction mixture into excess cold hexane/methanol (85/15, v/v) twice, followed by overnight vacuum drying at 65 °C (yield, >80%).

2.3. Synthesis of Poly(PLLA/PDLLA urethane) (PLDU) Elastomers and Film Casting PLA stereoisomers-based poly(PLLA/PDLLA urethane) elastomers are denoted as PLDU, where P represents poly, L is for PLLA, D for PDLLA, and U is for urethane. During the synthesis, PLLA-diol and PDLLA-diol prepolymers at different feed weight ratios were applied to finely tune the Tg close the physiological temperature. HMDI was used as a coupling reagent and the amount added was fixed at –OH/–NCO ratio of 1:1.2 in all reactions to facilitate the allophanate branching or crosslinking structure.42, 43 As a representative example, 2.0 g of PLLA-diol (Mn = 2300, 8.7×10-4 mol) and 2.0 g of PDLLA-diol (Mn = 2400, 8.3×10-4 mol) were mixed in a flask at 85 °C under high vacuum overnight. 30 mL of anhydrous DCE was then added to the flask, and any trace of water in the system was removed by azeotropic distillation leaving behind approximately 15 mL of DCE. After that, 0.34 g of HMDI (2.04 × 10−3 mol) and two drops of DBTL (∼8 × 10−3 g) were added sequentially and stirred at 85 °C under a nitrogen atmosphere for 24 h. The resultant mixture was then poured into a Teflon dish and the solvent was evaporated for 24 h in an oven at 60 °C. Smooth films were obtained after further drying of the samples under vacuum for 24 h. A series of PLDU elastomers were prepared through this method. The polymer compositions and molecular characteristic are listed in Table 1.


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2.4. Characterization The gel fractions of PLDU elastomers were determined by extraction with chloroform in a Soxhlet extraction apparatus until the weight of insoluble polymers did not change. After drying the insoluble parts at 60 °C for 12 h, the gel fraction was calculated according to the following equation: Gel fraction (%) = Wg/W0 × 100% (1), where W0 and Wg are the weights of the initial polymer and dried insoluble part of the sample, respectively.44 The crosslinking density of PLDU elastomers were determined by previously reported titration method.43 Typically, a known amount of PLDU elastomer was placed in butylamine (BuNH2)/CHCl2 solution (2.0 × 10-5 mol/g), and refluxed at 50 °C for 24 h. The unreacted BuNH2 was back-titrated with HCl/ethanol (0.01 mol/L) solution with bromophenol blue as an indicator. Since PLDU elastomers were partially cross-linked, the soluble fraction as extracted by chloroform was subject for further molecular analysis. 1H and

13

C Nuclear

Magnetic Resonance (NMR) spectra were recorded on a Bruker AV-400 NMR spectrometer at room temperature. Chemical shift at 7.3 ppm were referred to the solvent peaks CHCl3. Gel Permeation Chromatography (GPC) analysis was carried out with a Shimadzu SCL-10A and LC-8A system equipped with a Shimadzu RID10A refractive index detector. THF was used as the eluent at a flow rate of 1.0 mL/min at 40 °C. The molecular weights and the polydispersities of the soluble PLDU fractions used in this study are summarized in Table 1. Fourier Transform Infrared Spectroscopy (FT-IR) was performed using PerkinElmer Spectrum 2000. The data were collected in the range of 400 to 4000 cm-1 with a resolution of 4 cm-1 and a scan number of 64 at room temperature. Wide Angle X-ray Scattering (WAXS) was carried out on Bruker GADDS X-ray diffractometer with an area detector, operating under Cu Kα (1.5418 Å) radiation (40 kV, 40 mA) at room temperature.



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Thermogravimetric analysis (TGA) measurements were performed on a TA Q500. All samples were heated at 20 °C/min to 800 °C under nitrogen at a flow rate of 60 mL/min. Differential Scanning Calorimetry (DSC) were performed on TA Instruments 2920 differential scanning calorimeter with an auto-refrigerated cooling system and calibrated using

indium. Each sample was tested by the following

protocol: heating from room temperature to 200 °C at 10 °C/min, holding at 200 °C for 2 min, cooling from 200 to -80 °C at 10 °C/min, and reheating from -80 to 200 °C at 5 °C/min. Glass transition temperatures (Tg) were taken as the midpoint of the stepwise decrease of the re-heating flow trace.45, 46

2.5. Thermomechanical Properties Viscoelastic thermomechanical properties of PLDU elastomers were conducted in a tensile mode using dynamic mechanical analyzer (DMA Q800, TA Instruments, USA).46 Samples were cut from the casted films to feature dimensions of 30 mm × 5 mm × 0.8 mm. The samples were loaded on a clamp and measured at a heating rate of 3 °C/min from -30 to 100 °C. A frequency of 1 Hz was used for all measurements. The same samples were also subject to tensile test at a controlled force rate of 0.2 N/min at room temperature.

2.6. Shape Memory Properties Shape memory properties of PLDU elastomers were investigated by DMA. The same samples used in thermomechanical property were applied in shape memory behavior measurements. The typical thermocyclic run consisted of four steps: (A) each sample was first equilibrated at 60 °C and elongated to a force of 3 N at a rate of 0.2 N/min, (B) cooled to 0 °C at a rate of 3 °C/min with an isothermal period of 5 min, (C)


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unloaded to 0.001 N at a rate of 0.2 N/min, and (D) reheated to 60 °C at a rate of 3 °C/min with an isothermal period of 5 min. This process was repeated multiple cycles to determine the shape fixing ratio (Rf) and shape recovery ratio (Rr).22, 47-49

=

− ( ) ( ) (2) = (3) − ( − 1)

Where (N) is the strain of the sample after the stress is released in the Nth cycle, is the maximum strain the specimen experiences when it is stretched and fixed at 0 °C and (N-1) and (N) is the strain in the unloaded specimens in two successively passed cycles before a tensile stress is applied. The shape memory recovery process was also recorded by a series of photographs.

3. Results and Discussion 3.1. Synthesis and Characterization of PLDU Elastomers The diverse isomeric forms of PLA have led to a multitude of polymer chains and crystal structures, which provided great opportunities for enhancement of material properties through the combination of various PLA stereoisomers.16, 18 Previously, we reported the synthesis of amphiphilic copolymers by copolymerizing hydrophobic enantiomeric PLLA or PDLA with different hydrophilic components such as poly(acrylic acid) (PAA), poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide) (PNIPAAm) and poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) in various architectures, and investigated their PLA stereocomplexation induced selfassemblies in aqueous solutions.17, 20, 50-52 However, in the present study, we described the design of amorphous PLA stereoisomers-based poly(PLLA/PDLLA urethane) (PLDU) elastomers and investigated their structure-property relationship in shape



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memory applications. PLDU elastomers were synthesized from polyurethane reaction between –OH on telechelic PLLA and PDLLA macrodiols and –NCO on HMDI. The synthetic route of this type of main reaction is presented in Scheme 1. However, allophanate branching or the partially cross-linked structure was also created in PLDU by the secondary reaction between the urethane linkage and slightly excess amount of isocyanate, as indicated in Figure S1.42 This unique architecture was deliberately designed as the branch points, which is requisite to facilitate shape memory effect in amorphous polymer networks.6 At predetermined –NCO/–OH ratio of 1.2:1, the crosslinking density in the range of 4.7 – 5.2 mol/m3 was obtained (Table 1). As the cross-linked networks restricted the chain mobility, a gelation process occurred during the chain-extension reaction. The degree of gelation was reflected by the gel fraction in PLDU elastomers. In this study, the gel fraction was found to be 3.4 – 4.3 wt%, which is relatively lower than previously reported poly(butylene succinate) (PBS) and poly(1,2-propylene succinate) (PPSu) polyurethane networks prepared at higher – NCO/–OH ratios (20 – 58 wt%).44 This can be explained as that the apparent but still low crosslink density can just form a slightly cross-linked or branched structure, which is not compact enough to accommodate the solvent. Similar behavior has been also reported in polyurethanes based on hydroxyl terminated polybutadiene and toluene diisocyanate.53, 54


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Scheme 1. Synthetic procedure of PLA stereoisomers-based poly(PLLA/PDLLA urethane) (PLDU) elastomers

A series of PLDU elastomers containing various PLA stereoisomers were synthesized. Since PLDU elastomers were partially cross-linked, the soluble fraction as extracted by chloroform was further analysed and the molecular characteristics are summarized in Table 1. The relative molecular weight and polydispersity of the soluble fractions of the PLDU elastomers as extracted by chloroform were determined from GPC and the results are presented in Table 1. As a typical example shown in Figure 1, PLDU-1 shows a nearly symmetrical and unimodal peak of the molecular weight distribution and non-overlapping nature of the plot with those of corresponding precursors, indicating a complete reaction with no unreacted precursor remaining. In addition, PLDU-1 experiences a shorter elution time as compared to PLLA-diol and PDLLAdiol traces. This confirmed the successful chain-extension reaction between the



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bifunctional compounds which led to the formation of a polymer with high molecular weight.19, 55

Figure 1. GPC profiles of (A) Poly(PLLA/PDLLA urethane), PLDU-1, and its precursors (B) PLLA-diol and (C) PDLLA-diol.

The chemical structure of PLDU elastomers was verified by NMR spectroscopy. Figure 2 shows the 1H NMR spectra of extracted PLDU-2 in CDCl3. The peaks associated with the methyl and methine protons of PLA stereoisomers were identified at δ 1.57 and 5.16 ppm, respectively.56 The chemical shift at δ 4.32 ppm is assigned to the urethane group generated from the reaction between hydroxyl groups and isocyanate groups in of HMDI, and the methylene protons adjacent to the urethane group were also detected at δ 3.14 ppm, as reported previously.10, 57 For 13C NMR, the signals corresponding to carbonyl carbon peak of HMDI were observed at 122.89 ppm.58 After polymerization, the 13C peak of the carbonyl carbon of the newly formed urethane linkage was observed at 156.0 ppm as presented in Figure 3. 14 ACS Paragon Plus Environment

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Figure 2. 1H NMR spectra of Poly(PLLA/PDLLA urethane), PLDU-2 in CDCl3.

Figure 3. 13C NMR spectra of Poly(PLLA/PDLLA urethane), PLDU-2 in CDCl3.

This shift was attributed to the attachment of the hydroxyl groups to the isocyanate functional groups in the formation of the urethane linkage.58 Due to the low fraction of allophanate linkage in solvent extracted component of PLDU and its overlapping 15 ACS Paragon Plus Environment


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with urethane linkage, the signal for carbonyl carbon of allophanate linkage was not well resolved in NMR spectra. However, the rest of the signals ascribed to respective urethane linkages and PLA stereoisomers were found in a well-split state, as labelled in Figure 2 and 3. This observation, together with the concomitant increase in the molecular weight of the polymers, indicates the successful polymerization reaction.

Table 1. Molecular characteristics of Poly(PLLA/PDLLA urethane) elastomers and their prepolymers

Samples

a

Compositions in Elastomer ν [Mn]/kDa c PDI c Gel Fraction (wt %) b (wt %) e (mol/m3) f PLLA PDLLA

PLLA-diol

-

-

2.3

1.1

-

-

PDLLA-diol PLDU-1

10

90

2.4 86.2

1.2 1.7

3.8

5.0

PLDU-2

20

80

92.7

1.8

4.3

5.2

PLDU-3

30

70

82.4

1.6

3.4

4.7

PLDU-4

50

50

93.5

1.8

3.6

4.9

a

Poly(PLLA/PDLLA urethane)s are denoted PLDU, where P represents poly, L is

for PLLA, D for PDLLA, and U is for urethane.

b

Feed ratios as put in the samples

preparation at isocynate/hydroxyl (NCO/OH) equivalent ratio of 1.2:1. c Determined by gel permeation chromatography (GPC) measurements of the soluble fractions of PLDU elastomer.

e

Gel fraction (Wt%) = 100*Wg/W0, Where W0 and Wg are the

weights of the initial polymer and dried insoluble part of sample, respectively. Crosslinking density determined by the amine-decomposition method.


f

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Figure 4. FTIR spectra of (A) Poly(PLLA/PDLLA urethane), PLDU-2, and its precursors (B) PDLLA-diol and (C) PLLA-diol.

FTIR is a useful tool in the characterization of the functional groups present in the polymer. As a typical example, Figure 4 shows FTIR spectra of PLDU-2 and its PLLA-diol and PDLLA-diol precursors. One can see that PLDU-2 shows a strong characteristic band near 1755 cm-1 due to the C = O stretching vibration. An accompanying weak band at 2950 – 3000 cm-1 was attributed to the vibration of C–H in methine and methyl groups.18 In addition, the two new absorption bands at 1530 and 3410 cm-1 were the indication of NH deformation and stretching modes of the urethane link.59 Together, the FTIR, GPC and NMR results provide a solid justification for the successful synthesis of PLDU elastomers.

3.2. Thermal and Mechanical Properties of PLDU Elastomers Thermal stability of PLDU elastomers were evaluated using TGA. A typical TGA curve for PLDU-1 is presented in Figure 5 together with the two telechelic precursors PLLA-diol and PDLLA-diol. As presented in Figure 5, both precursors showed a 17 ACS Paragon Plus Environment


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single-step degradation profile. The onset temperatures that led to 5.0 wt% weight loss were 204.5 and 200.9 °C for PLLA-diol and PDLLA-diol, respectively. On the other hand, the presence of polyurethane formation in PLDU elastomers showed a two-phase degradation in a stepwise process. The thermal degradation temperature was shown to have increased by 40 – 45 °C for the PLDU elastomers compared with that of PLA stereoisomers, implying that the polymerization of PLA stereoisomers in urethane formation would make PLDU elastomers more thermally stable than the parent precursors.57

Figure 5. TGA curves for (A) Poly(PLLA/PDLLA urethane), PLDU-1, and its precursors (B) PLLA-diol and (C) PDLLA-diol.

DSC was used to determine the glass transition temperature (Tg) and crystallization property of PLDU elastomers. Figure 6 shows the DSC thermogram of the as-casted PLDU elastomer films and their precursors. Numerical values corresponding to the thermal transition are tabulated in Table 2. The stereopure PLLA-diol prepolymer 18 ACS Paragon Plus Environment

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exhibits Tg and Tm of 35.1 °C and 112.0 °C, respectively, which is about 35 °C and 60 °C lower than the previously reported high molecular PLLA.27 In a similar molecular weight range, no crystallization and melting behavior were detected for PDLLA-diol. This is because of the heterochiral carbon configurations in the polymer chains which disordered the crystallinity structure.60 In addition, the disordered chains allowed for more motion even at lower temperatures that manifested itself by lower Tg. In this study, the Tg of PDLLA-diol is about 16 °C lower than for the PLLA-diol. Since the thermal properties of PLA depend strongly on molar mass and proportion of stereoisomers in polymer chains, it became a motivation to modulate the Tg of PLDU elastomers close to physiological range by combining different PLA stereoisomers and adjusting their constitutional ratios in a polyurethane network. This strategy could have the potential to reduce the high transition temperature reported in previously developed Tg-dependent PLA shape memory polymeric system.6, 33

Figure 6. DSC curves of Poly(PLLA/PDLLA urethane)s and its precursors. (A) PDLLA-diol, (B) PLLA-diol, (C) PLDU-1, (D) PLDU-2, (E) PLDU-3 and (F) PLDU4. 19 ACS Paragon Plus Environment


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Table 2. Thermal-mechanical properties of Poly(PLLA/PDLLA urethane) elastomers

Samples

a

Tg DSC (°C) a

E′ 0°C (MPa) b

E′ 60°C (MPa) c

f g e Tα (°C) d E (MPa) σb (MPa) εb (%)

Td h

ρ (MJ/m3) i

PLLA-diol

35.1

-

-

-

-

-

-

204.5

-

PDLLA-diol PLDU-1 PLDU-2 PLDU-3 PLDU-4

19.0 38.9 40.5 44.3 46.8

1547.0 1802.6 2039.1 2040.0

9.2 12.1 22.4 13.7

42.1 43.5 44.6 45.2

4.97 8.17 8.24 39.40

1.53 2.09 2.88 4.34

414.0 427.8 439.3 417.8

200.9 244.1 241.8 246.2 243.4

0.23 0.56 0.64 0.79

Glass transition temperatures as determined from the DSC runs. b Storage moduli of the glassy state determined at 0 °C. c Storage moduli of the

elastic state determined at 60 °C. d Maximum α relaxation temperature obtained on the Tanδ-temperature curves. e Elastic modulus. f Stress at break.

g

Strain at break. h Decomposition temperature recorded at 5% weight loss at the TGA thermograms. i Energy density calculated from

stress-strain curve.

20

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As shown in Figure 6, all the synthesized PLDU elastomers exhibit a single Tg with no melting endotherm. The presence of only a single Tg confirmed the good miscibility between PLLA and PDLLA in PLDU elastomers.13 In addition, the lack of melting peaks in DSC traces suggested that PLDU elastomer films were amorphous with no crystalline regions, even with the incorporation of crystalline PLLA up to 50 wt%. This is probably due to the urethane formation and allophanate linkages that act as branch points in PLDU networks rather than creating a regular multiblock copolymer structure containing PLLA and PDLLA chains. The presence of the branch points in the partially cross-linked PLDU elastomers could inhibit the chain segment mobility and hinder regular packing orientation as required for a crystalline structure.42,

43

The amorphous characteristics of PLDU elastomers were also

investigated by wide-angle X-ray diffraction (WAXD). As shown in Figure S2, PLLA macrodiol exhibits diffraction peaks at 2θ values of 14.7°, 16.6°, 19.1°, and 22.5°, corresponding to the α-form homocrystallites,61 while these peaks are not present in PLDU elastomers, even with the incorporation of crystalline PLLA at 50 wt% in PLDU-4 (Figure S2, curve C). WAXD study confirmed the completely amorphous behavior of PLDU elastomer. Moreover, the Tg of the amorphous PLDU elastomers shifted to a high temperature with increasing PLLA content (Table 2). This shift in Tg was taken as an indication for the differences encountered in PLLA/PDLLA phase mixing in PLDU elastomers.59 The higher the content of the hard component, the more restrictive the chain mobility would become which leads to a higher Tg.62 For example, when the PLLA content was increased from 10 to 50 wt% in PLDU elastomers, the corresponding Tg was found in an increasing trend from 38.9 to 46.8 °C (Figure 6 and Table 2). The Tg obtained in this study is significantly lower (~ 15 °C) than previously reported amorphous PLA shape memory polymer networks,



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indicating the successful modulation of the thermal transition temperature by designing PLA stereoisomers in polyurethane formation.6,

33

Unlike linear high

molecular weight PDLLA (Tg ~ 54 °C) and PLLA (Tg 60 – 70 °C), the Tg exhibited by PLDU elastomers are more suitable for biomedical applications.63

Figure 7. Storage modulus (E′) of Poly(PLLA/PDLLA urethane) elastomers. (A) PLDU-1, (B) PLDU-2, (C) PLDU-3 and (D) PLDU-4.

To function as a thermally responsive SMP, of paramount importance is the control of thermo-mechanical properties, particularly PLDU elastic moduli and transition temperatures. As such the PLDU elastomers at various PLA stereoisomer ratios were compared with one another using DMA in tensile mode. The storage modulus (E′) and loss tangent (tan δ) are shown in Figure 7. For the elastic modulus curves, it was found that all the investigated PLDU elastomers were in glassy state with almost unchanged tensile storage modulus in the temperature range of T < Tg. The E′ of


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PLDU elastomers is dependent on PLA stereoisomer compositions, showing an increment of the storage moduli at higher PLLA content. For example, the storage moduli determined at 0 °C increased from 1547.0 to 2040.0 MPa when the PLLA increased from 10 to 50 wt% (Table 2 and Figure S3). This could be explained by the more prominently reduced chain mobility at higher content of hard component. This result is in accordance with that obtained from DSC measurements. When the temperature is higher than Tg, the E′ of all PLDU elastomers displays a sharp decrease due to the increased molecular mobility, which could allow for the stored elastic energy to be released as a mechanical restoring force and for the material to recover its permanent original shape.41, 64 For instance, comparing to the E′ greater than 1500 MPa at 0 °C, the E′ dramatically dropped to a value of about 9.2 – 22.4 MPa at 60 °C, suggesting the thermal transition from glassy to rubbery state of PLDU elastomers during the heating (Table 2). It was previously reported that the large modulus loss at the transition temperature is a prerequisite for the material to exhibit shape memory effect and the higher storage modulus in the glassy state would be beneficial to the shape fixation of PLDU elastomers at low temperature.65 In correspondence to the modulus step, the variation of tan δ with temperature for all PLDU elastomers was also shown in Figure 7.

The loss tangent exhibits a α

relaxation peak near the glass transition temperature. The maximum α relaxation temperature (Tα) recorded on the tan δ-T curves did not correlate well with the Tg data obtained by DSC analysis due to the well-known frequency effect.66 However, tan δ-T curves corresponded with the E′ and all the PLDU elastomers featured a softening transition breadth over the physiological to tissue-burning temperature range, indicating the shape recovery of these samples in a temperature range ideal for



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implantable medical devices and surgical tools.46 In addition, both Tα and Tg followed a common trend with changing the PLA stereoisomer composition, indicating the miscibility of the components in PLDU elastomers.41, 66

Figure 8. Strain-stress curves of Poly(PLLA/PDLLA urethane) elastomers. (A) PLDU-1, (B) PLDU-2, (C) PLDU-3 and (D) PLDU-4.

Figure 8 shows the stress – strain curves of PLDU elastomers with different PLA stereoisomer composition at room temperature. It was noted that all the samples display a typical elastomeric behavior having an elongation at break (εb) greater than 400% and no yield point. In addition, the elastic moduli (E) and stress at break (σb) were found to be in the range of 4.97 – 39.4 MPa and 1.53 – 4.34 MPa, respectively. Due to the completely amorphous behavior of PLDU elastomers, these values are markedly lower than the previously reported semi-crystalline PLLA/1,4-butanediol (BDO) polyurethane SMPs.67 On the other hand, both E and σb increased with the


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increasing amount of PLLA and they can be easily controlled by adjusting the different PLA stereoisomer composition in PLDU elastomers (Table 2 and Figure S3). The differences in chain interactions between PLA stereoisomers, as reflected by the Tg in DSC results, may cause the different mechanical behavior of PLDU elastomers.66 For example, PLDU-4, having Tg well above the other three samples, is characterized by having the highest elastic modulus and stress at break (Table 2). Hence, it is the toughest and most ductile among the PLDU elastomers (Figure 8).

3.3. Shape Memory Behavior of PLDU Elastomers The shape memory behavior of PLDU was quantitatively assessed by dynamic mechanical analysis (DMA), in which the changes of strain (ε), stress (σ), and temperature (T) were measured. Figure 10 shows the results of a typical shape memory experiment performed on PLDU-2, in a three-dimensional graph. The initial position marked as asterisk represents the permanent shape at 60 °C with no strain and no stress applied. Path A is a stress – strain curve (σ vs ε) at a constant temperature of 60 °C. At this temperature, the deformation process was carried out by ramping to a load of 3.0 N to create a strained strip with a temporary shape. Such a temporary deformation was then fixed by cooling the sample to 0 °C, during which the load was maintained (Figure 9, Path B). Next, the load was removed in Path C to allow for evaluation of shape fixity (Rf) by measuring the extent of strain difference. Shape recovery process is represented by Path D in Figure 9, carried out at a constant heating rate of 3.0 °C/min to 60 °C. The ability of the sample to recover to its permanent shape after each deformation cycle was quantified by the shape recovery ratio (Rr). The results of shape fixity and recovery ratio of PLDU elastomers calculated by the thermocyclic measurements are tabulated in Table 3. Elastic work energy density is an increasingly important parameter

of shape memory polymers. In this study, the elastic energy density of PLDU elastomers was calculated according to the previously reported method, as detailed in 25 ACS Paragon Plus Environment


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section S1.68, 69 As shown in Table 2, the energy density of PLDU elastomers were found to be adjustable, following an increasing trend from 0.23 – 0.79 MJ/m3 when the PLLA increased from 10 to 50 wt%. It has been mentioned that an ideal elastic energy storage materials is stiff yet can be elongated to high levels of the strain and can effectively fix and maintain imposed strain upon cooling.69 However, it is noted that there is no strong correlation between the energy density and shape recovery.

Figure 9. Typical stress–strain–temperature diagram for Poly(PLLA/PDLLA urethane), PLDU-2, in a three-cycle thermocyclic measurement. The asterisk marks the beginning of the cycle and the arrows denote the various stages, specifically (A) deformation, (B) cooling, (C) unloading and (D) recovery.

From the thermocyclic curves in Figure 9, the Path B for PLDU-2 shows a ∼ 7% creep which was occurred between the elongation and fixing step. Excellent shape 26 ACS Paragon Plus Environment

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fixing Rf > 99% was observed for the first and each subsequent cycles, indicating that all the induced strain was completely preserved once the applied load is removed.46 Good shape fixity is of great importance for applications such as medical devices as it is crucial for the material to be able to maintain its temporary shape well.5 As presented in Table 3, all the PLDU elastomers show good shape fixity ratios > 99%. Figure 9 also shows that the shape recovery for PLDU-2 is not complete for the first cycle and a residual strain of 8.0% is detected. However, an excellent shape recovery ratio Rr close to 100% was observed after one complete cycle of the shape memory experiment and it showed very similar and stable behavior in the subsequent thermocyclic measurements. This is due to the segment-chain orientation and relaxation effects in the as-cast film and an initial conditioning is required before ideal properties are obtained.5, 6, 70 From Table 3, it is evident that in all other cases the shape recovery effect is also good after one deformation cycle, with general shape recovery ratios of 70.9 to 95.1% for cycle two and three, respectively. As discussed in the DMA studies, the good shape recovery effect may result from the remarkably altered elastic modulus of PLDU elastomers from glassy state to rubbery state at different temperatures (Table 2).71 In addition, no diffraction peaks were observed in the specimen before and after stretching, indicating the completely amorphous nature of the film during the measurement (Figure S2). This result suggests that the shape memory behavior of the PLDU films is mainly due to the branched structure and chain interactions in PLDU elastomers rather than crystallization induced shape memory effect in Tm-dependent SMPs.7 To further elaborate the structure-property correlation, thermocyclic measurement of linear poly(PLLA/PDLLA urethane) specimen with similar composition to PLDU-2 was conducted for comparison. As presented in Figure S4, the shape recovery is not complete even at lower deformation



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ratio of 32% and a residual strain of 17% is detected in the first cycle. In addition, the recovery efficiency decreased significantly with increasing number of shape memory cycles (

Control of PLA Stereoisomers-Based Polyurethane Elastomers as

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