Article pubs.acs.org/Biomac
Poly(glycerol sebacate urethane)−Cellulose Nanocomposites with Water-Active Shape-Memory Effects Tongfei Wu,†,‡ Martin Frydrych,†,‡ Kevin O’Kelly,§ and Biqiong Chen*,‡ ‡
Department of Materials Science and Engineering, University of Sheffield, Mappin Street, Sheffield, S1 3JD, United Kingdom Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, College Green, Dublin 2, Ireland
§
ABSTRACT: Biodegradable and biocompatible materials with shape-memory effects (SMEs) are attractive for use as minimally invasive medical devices. Nanocomposites with SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and renewable cellulose nanocrystals (CNCs). The effects of CNC content on the structure, water absorption, and mechanical properties of the PGSU were studied. The waterresponsive mechanically adaptive properties and shape-memory performance of PGSU-CNC nanocomposites were observed, which are dependent on the content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited the best SMEs among the nanocomposites investigated, with the stable shape fixing and shape recovery ratios being 98 and 99%, respectively, attributable to the formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In vitro degradation profiles of the nanocomposites were assessed with and without the presence of an enzyme.
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INTRODUCTION Materials with shape-memory effects (SMEs) have the capability of recovering their shape upon exposure to an external stimulus.1 Since the successful application of shapememory metal alloys (in particular, nickel−titanium alloys) in biomedical devices (e.g., venous filter, cardiac valves and stents),2,3 numerous structures with SMEs based on polymers (especially polyurethane-based polymers) have been developed4 and investigated for biomedical potentials such as catheters, orthopedic and dental surgeries, artificial skins, wound closures, and surgical sutures.5 Shape recovery can be activated by various stimuli, such as temperature changing,6−9 pH changing,10 light radiation,11−13 solvent absorption,14 and exposure to a specific chemical.4,15 Recently, research interest into materials with water-active SMEs has been growing,16 because they use body fluids (mainly water) as the stimulus rather than body temperature. Wateractive SMEs have been observed in polymers and elastomer composites filled with hydrophilic particles, such as polyurethane−poly(ethylene glycol) block copolymers,14 thermoplastic polyurethane (TPU)−cellulose nanocrystal (CNC) nanocomposites,17−22 TPU−clay composites,23 and TPU− particular poly(vinyl alcohol) composites.24 The ingredient to induce water-active SMEs in these materials is a resilient physically or chemically cross-linked network with a reversible switching transition of modulus triggered by water absorption or desorption,25 due to the plasticizing effect of water molecules.26 Cellulose is the most abundant polymer in nature.27 CNCs can be obtained by removing the amorphous phase from cellulose by hydrolysis under controlled acidic conditions.28,29 © 2014 American Chemical Society
The elastic modulus of CNCs is experimentally determined as 70−140 GPa.30−33 Cellulose is degradable by enzymes, yielding glucose,34 and has been used as in vivo supports for the growth and differentiation of stem cells.35,36 Due to their green sources, stiffness, and biocompatibility, CNCs have also been considered as a reinforcement material for biopolymers, and the resulting biocomposites have been studied as tissue scaffolds.34,37,38 According to previous research,29 CNCs are able to form a high-modulus and interconnected CNC network in the polymer matrix via hydrogen bonding. For instance, the modulus of the dry percolated CNC network is 1000 times higher than that of the TPU matrix.39 This huge difference in modulus guarantees the shape fixing ability of the TPU−CNC composite by resisting the resilient force of the deformed matrix. Upon wetting, water breaks down the hydrogen bonding between individual hydrophilic CNC fillers, leading to the softening of the filler network and hence the shape recovery under the resilient force of the deformed matrix.15,18,19,40 Since Lendlein and Langer reported a biodegradable polymer with thermoactive SMEs and demonstrated its potential in medical application in 2002,41 an increasing number of studies has focused on developing biodegradable polymers with SMEs.10,42 When used in a stimulus-responsive surgical tool or another implantable device for treatment of diseases, biodegradable polymers with SMEs allow for minimally invasive surgery for insertion of the device into the body41 and avoid a Received: April 7, 2014 Revised: May 28, 2014 Published: May 30, 2014 2663
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second surgery to remove the device from the body. In this work, we report a new type of nanocomposite with water-active SMEs that are prepared from CNCs and a poly(glycerol sebacate) (PGS) derivative. PGS is a biodegradable and biocompatible elastomer,43 which has been explored as a material for the construction of soft tissue scaffolds43−45 and has recently been investigated as a potential temperature-active shape-memory material.46 The conventional synthesis of PGS is composed of polycondensation of glycerol and sebacic acid to form a PGS prepolymer followed by the cross-linking of prepolymer chains at an elevated temperature and under vacuum.43 Because of the severe conditions required for the cross-linking step, the application of PGS is limited, and as a result, many studies have been carried out to modify the structure of PGS by, for example, attaching a functional group (e.g., acrylate for photocuring) to make the processing of PGS more cost-effective and versatile for biomedical applications.47,48 Recently, Pereira et al. reported that PGS prepolymer could be readily cross-linked by an isocyanate via the reaction with the hydroxyl groups from the prepolymer to form poly(glycerol sebacate urethane), denoted by PGSU, which demonstrated biodegradability and tunability in mechanical properties.49 Based on this development, PGSU−CNC nanocomposites with different contents of CNCs were prepared in this work and investigated as degradable water-active shapememory materials for potential uses as body-fluid responsive medical devices.
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Figure 1. Scanning electron microscopy images of cellulose nanocrystals. cooling, desired amounts of the DMF solution of PGSU prepolymer (pre-PGSU) and the CNC dioxane suspension were weighed and mixed under stirring for 5 h. The mixture was then cast onto a Teflon disk, which was kept in a fume cupboard for 3 days and subsequently in a vacuum oven at 30 °C for 2 days to evaporate the solvent and to further cross-link the pre-PGSU into PGSU.49 Then, the cast dry films were immersed in excess ethanol for 24 h at room temperature to remove the un-cross-linked components. PGSU−CNC nanocomposite films were obtained after drying in a vacuum oven for 8 h at 50 °C. The thicknesses of the final films were between 0.15 and 0.25 mm. Measurements. The weight percentages of the un-cross-linked components (Wun‑cross‑linked) for PGSU in PGSU−CNC nanocomposites were calculated by eq 1. Five specimens were tested for each sample.
EXPERIMENTAL SECTION
Materials. Cellulose microcrystals (Type 20), glycerol (>99%), sebacic acid (99%), hexamethylene diisocyanate (HDI, 99%), stannous 2-ethyl-hexanoate (95%), sulfuric acid (95−98%), 1,4-dioxane (anhydrous, 99.8%), dimethylformamide (DMF, anhydrous, 99.8%), phosphate buffered saline (PBS) tablets, and lipase enzyme from porcine pancreas (54 U mg−1) were purchased from Sigma-Aldrich and used as received, unless otherwise specified. Preparation of Cellulose Nanocrystals (CNCs). CNCs were prepared from cellulose microcrystals by acid hydrolysis following the procedure reported elsewhere.50−52 Briefly, 100 g of 64 wt % sulfuric acid and 5 g of cellulose microcrystals were mixed at 45 °C for 60 min with strong stirring. The mixture was diluted by 500 mL of distilled water, and CNCs were collected by centrifugation. CNCs were washed by centrifugation with distilled water until a neutral pH value was reached and then washed with 1,4-dioxane three times to remove water. CNCs were dispersed in 1,4-dioxane and kept for preparation of PGSU−CNC nanocomposites after ultrasonication (UP200S, Hielscher) at 200 W and 24 kHz for 2 min. Five grams of CNC 1,4-dioxane suspension were weighed and fully dried to determine the concentration of CNCs, which was 3.7 wt %. The CNCs prepared using this method have a length below 2 μm and a maximum width in the range of 200−300 nm (Figure 1, inset), giving an approximate average aspect ratio of 11.8. The dimensions of CNCs depend on the source of cellulose and acid hydrolysis conditions.50,53 CNCs in agglomerates are also depicted in Figure 1, showing the potential for CNCs to form a percolated network, as reported in the literature.17−22 Synthesis of Poly(glycerol sebacate urethane)−CNC Nanocomposites. Poly(glycerol sebacate urethane) was synthesized through two steps according to previous literature, with a modification.43,49,54 Briefly, PGS prepolymer was first synthesized through the polycondensation of equimolar amounts (0.05 mol) of glycerol and sebacic acid. The mixture was allowed for reaction at 120 °C under a nitrogen flow for 8 h and then at 120 °C in a vacuum oven for 16 h to yield a viscous prepolymer. After cooling, 10 g of PGS prepolymer was dissolved in 100 mL of DMF. The catalyst stannous 2ethyl-hexanoate (0.05% w/v) and cross-linking agent HDI (HDI: glycerol = 0.3:1) were added to the DMF solution. The reaction flask was purged with nitrogen, sealed, and kept at 55 °C for 5 h. After
Wun ‐ cross ‐ linked =
W1 − W2 × 100% Wpre ‐ PGSU
swelling degree =
Wwet − Wdry Wdry
(1)
× 100% (2)
Here, Wun‑cross‑linked for PGSU in the as-cast PGSU−CNC nanocomposites was determined by measuring their weights before ethanol extraction (W1) and weights after the extraction and drying (W2). Wpre‑PGSU is the feeding amount of pre-PGSU. The aqueous swelling degree of PGSU−CNC nanocomposites was determined by measuring their weights before immersion (Wdry) and weights after immersion in distilled water (Wwet) for a specific time period (e.g., 5 min, in this case) at room temperature (22 °C), given by eq 2. To minimize the error in measuring the water uptake, once the wet samples were taken out of water, they were placed on paper tissue to remove water from the surface, immediately put in a plastic container, and then weighed. Five specimens were tested for each material. Fourier transform infrared spectroscopy (FTIR) was carried out on a Spectrum 100 spectrophotometer (PerkinElmer) with attenuated total reflectance in the wavenumber region of 4000 to 400 cm−1, with a resolution of 1 cm−1. Scanning electron microscopy (SEM) was executed at an acceleration voltage of 10 kV (Inspect F, FEI). To observe the fracture surface of nanocomposites, the sample was fractured in liquid nitrogen in a direction perpendicular to the stretch direction, and the fracture surfaces were sputter-coated with gold using an SPI sputter coater for enhanced conductivity before SEM was conducted. For SEM observation of CNCs, a drop of CNC dioxane suspension was placed on a clean glass slide, which was sputter-coated with gold after evaporation of the solvent. 2664
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Tensile tests were carried out using a Lloyd universal testing machine (Ametek Inc.) at a speed of 50 mm·min−1. Samples for the tensile tests were cut from cast films in a rectangular shape (2.5 mm × 50 mm). A 50 N load cell was used and the distance between the sample grips was 30 mm. Five specimens were tested for each material. Dynamic mechanical analysis (DMA) of PGSU−CNC nanocomposites was conducted on a TA 800 dynamic mechanical analyzer (TA Instruments) in the tensile mode. The samples were tested from −50 to 30 °C with a temperature sweep of 2 °C·min−1 at a frequency of 1 Hz and a displacement of 0.05 mm (0.5% strain). For DMA with the presence of water, the samples were tested under isothermal conditions as a function of time at a frequency of 1 Hz and a displacement of 0.05 mm at ambient temperature (24 °C). Samples for DMA were cut from nancomposite films in a rectangular shape (2.5 mm × 50 mm). The shape-memory effects in two conditions (distilled water at ambient temperature (22 °C) and PBS solution (pH = 7.4) at 37 °C) were evaluated according to a method of wetting-stretching-drying cycles described by Zhu et al.40 Initially a straight strip of the film was immersed in the solution for 1 h. It was then removed from the solution and stretched to a strain εm (100%) at the corresponding temperature. After 100% strain being kept for 4 h to dry the sample, the residual strain εu(N) was measured in the stress-free state; N is the cycle number. The shape fixity ratio (Rf) was defined as eq 3. Finally, the strip was immersed in the solution again for 1 h to recover its original length and its residual strain εp(N) (εp(0) = 0) was measured in the stress-free state. The shape recovery ratio (Rr) was defined as eq 4. To start the next cycle, the strip was removed from the solution and stretched to 100% strain (based on the original length). Rf =
Rr =
εu(N ) × 100% εm
εm − εp(N ) εm − εp(N − 1)
Scheme 1. Synthesis of PGSU−CNC Nanocomposites
Table 1. Compositions of PGSU−CNC Nanocomposites
(3)
sample
pre-PGSU (g)
CNCs (g)
PGSU PGSU1 PGSU2 PGSU3 PGSU4 PGSU5 PGSU6
1.00 1.00 1.00 1.00 1.00 1.00 1.00
0 0.02 0.04 0.08 0.16 0.24 0.32
Wun‑cross‑linked (%)
WCNC (wt %)
ΦCNC (vol %)
± ± ± ± ± ± ±
0 2.51 4.89 9.29 16.8 23.3 28.6
0 1.90 3.72 7.15 13.2 18.6 23.2
23.6 22.7 23.0 23.6 24.3 25.7 26.7
2.5 1.9 3.1 2.8 3.3 2.9 2.3
has a statistically insignificant (p < 0.05) effect on the Wun‑cross‑linked, despite that the presence of −OH groups on the surface of CNCs may have competed with the −OH groups from PGS prepolymer to react with the isocyanate groups of HDI to form urethane linkages51,57 (Scheme 1). The weight percentages of CNCs (WCNC) in PGSU−CNC nanocomposites after the removal of the un-cross-linked components are listed in Table 1, column 5. Considering the values of density (ρ) to be 1.53 g·cm−3 for CNCs58 and 1.15 g·cm−3 for PGSU,47,59,60 the nominal volume percentages (ΦCNC) of CNCs in the PGSU−CNC nanocomposites are calculated according to eq 6 and summarized in Table 1, column 6. WCNC ΦCNC = × 100% WCNC + ρCNC (1 − WCNC)/ρPGSU (6)
× 100% (4)
In vitro degradation studies were performed on neat PGSU and PGSU−CNC nanocomposite with a CNC content of 28.6 wt % at 37 °C under a dynamic condition (100 rpm) in a shaker incubator (Stuart SI500) for up to 28 days in enzyme-free and enzyme-containing (110 U L−1; note: serum lipase in healthy adults is in the range of 30−190 U L−1)55,56 PBS solutions (pH = 7.4; 25 mL). The degradation medium was changed every day and after defined incubation days (1, 3, 7, 14, 21, and 28 days), all specimens were removed, washed with distilled water, and dried in a vacuum oven at 37 °C, until constant weight was achieved. The percentage of weight loss (wloss) was calculated by eq 5, w − wx wloss = 0 × 100% w0 (5) where w0 and wx are the initial weight before incubation and the weight measured at the given incubation day, respectively. Three specimens (thickness: 0.14−0.24 mm; width: 2−3.3 mm; length: 3.3−4.4 mm) were tested for each material. All specimens were first subjected to a sterilization procedure with pure ethanol and dried, before degradation studies were performed.
Figure 2 shows FTIR spectra of PGSU-CNC nanocomposites. As depicted in Figure 2a, the following typical cellulose bands are observed in CNCs in the range of 2000− 900 cm−1: O−H bending of absorbed water at 1643 cm−1; −CH2 wagging at 1315 cm−1; C−O−C asymmetric vibration at 1160 cm−1; glucose ring stretch (asymmetric) at 1107 cm−1; and C−O stretching in the range of 1083−947 cm−1.61,62 For neat PGSU, the peak near 1732 cm−1 is the carbonyl group stretching from ester and amide groups and peaks at 1618 and 1534 cm−1 are attributed to amide I and amide II of amide groups in urethane, the reaction product of HDI and hydroxyl groups. This indicates that the PGS prepolymer has been crosslinked with HDI to form PGSU, as previously reported.49 The peak at 1453 cm−1 is owing to −CH2 bending vibration.63 The presence of characteristic peaks of CNCs (1315 and 1083−947 cm−1) in the spectra PGSU−CNC nanocomposites evidence the successful incorporation of CNCs into PGSU. The effect of the incorporation of CNCs on the hydrogen bonding in PGSU
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RESULTS AND DISCUSSION Structural Characterization. The synthesis of PGSU employed in this study is a two-step process, that is, the condensation step and the cross-linking step (Scheme 1). CNCs were added in the second step for the formation of PGSU−CNC nanocomposites. The feeding amounts of PGSU and CNCs are shown in Table 1, columns 2 and 3, respectively. After the cross-linking step, the un-cross-linked components (including unreacted monomers, oligomers, and prepolymers) were removed following ethanol extraction, and their content Wun‑cross‑linked was determined and shown in Table 1, column 4. Wun‑cross‑linked is 23.6% for neat PGSU. The presence of CNCs 2665
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Figure 2. FTIR spectra of PGSU-CNC nanocomposites in the ranges of 2000−900 cm−1 (a) and 4000−2500 cm−1 (b).
is studied in the range of 4000−2500 cm−1 (Figure 2b). The bands at approximately 2920 and 2850 cm−1 arise from the asymmetric and symmetric −CH2 stretching.64 For CNCs, the wide peaks observed at 3333 and 3283 cm−1 are linked to the stretching O−H from the intramolecular and intermolecular hydrogen bonds. For PGSU, the wide peak at 3363 cm−1 is linked to the stretching O−H and N−H. This peak shifts to low wavenumbers (e.g., 3335 cm−1 for PGSU6) with increasing CNC content, indicating the formation of a strong interaction between PGSU and CNCs through hydrogen bonding.65 Successful incorporation of CNCs into PGSU can also be confirmed by SEM, from which ends of CNCs can be seen on the fracture surface of the PGSU−CNC nanocomposite (PGSU6) as white dots (Figure 3). These dots are present throughout the image, indicating CNCs are distributed throughout the PGSU matrix while possibly also forming a percolated network, as reported for TPU−CNC nanocomposites at the same filler content,19 due to the small size and high content of CNCs.
Figure 4. Typical tensile stress−strain curves (a) and tensile properties of PGSU−CNC: tensile strength and elongation at break (b), and Young’s modulus (c).
Tensile Properties. The effect of the addition of CNCs on tensile properties of PGSU is investigated by quasi-static mechanical testing. Figure 4a shows the typical stress−strain curves of PGSU−CNC nanocomposites, and the results are summarized in Figure 4b,c. The tensile strength, elongation at break, and Young’s modulus are 3.91 MPa, 493%, and 1.09 MPa for neat PGSU, respectively, which are, in general, close to the values (1.35 MPa, 516%, and 0.71 MPa, respectively) reported in the work of Pereira et al.49 The slight difference may be due to the tunable nature of PGSU; that is, the final cross-linked structure is sensitive to the reaction conditions. The presence of CNCs increases the tensile strength of PGSU up to 12.4 MPa (PGSU5), demonstrating the effective stress transfer from the matrix to the filler. When the CNC content is lower, the tensile strength increases with increasing CNC content while it decreases when the content increases further (from 18.6 vol % to 23.2 vol %). The drop in the strength may be because of the inferior network structure of CNCs arising from poorer dispersion and probably also the adverse effect of CNCs on the cross-linking reaction during the synthesis of PGSU. The elongation at break of PGSU−CNC nanocomposites decreases slightly with increasing content of CNCs. However, it remains at a relatively high level for all PGSU−CNC nanocomposites; for PGSU6, the elongation at break is 396%. Young’s modulus of PGSU−CNC nanocomposites increases with the content of CNCs. The improvements are 0.27, 0.36, 4.9, 21, 29, and 44 times for PGSU1, PGSU2, PGSU3, PGSU4, PGSU5, and PGSU6, respectively, in comparison with neat PGSU. Again, this is due to the effective reinforcement effect of CNCs on the elastomeric PGSU.
Figure 3. SEM image of the fracture surface of PGSU6. 2666
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be explained by the hydrodynamic effects of the filler in a viscoelastic medium and the mechanical restraint induced by the filler at the higher concentrations, which reduce the mobility and deformability of the matrix.69 In the rubbery region, E′ is improved by the incorporation of CNCs compared to neat PGSU and the improvement follows the same trend as occurred in the results of tensile tests. The α-relaxation of neat PGSU occurs mainly between −30 °C and −10 °C. The temperatures of α-relaxation (Tα) of the PGSU in nanocomposites are determined from the peak of tan δ in the curves shown in Figure 5b. They are −18.1, −16.7, −14.5, −5.9, −13.7, −17.3, and −20.3 °C for PGSU, PGSU1, PGSU2, PGSU3, PGSU4, PGSU5, and PGSU6, respectively. Tα of neat PGSU is lower than the glass transition temperature for the PGSU reported in the literature and investigated by differential scanning calorimetry (DSC), −11.8 °C.49 It is higher than or similar to the glass transition or α-relaxation temperatures reported for its base polymer PGS, namely, −37 °C measured by DSC in a study carried out by Cai and Liu,46 and between −30 °C and −40 °C measured by DSC and around −20 °C by DMA reported by Jaafar et al.69 The differences in these values may be attributed to different chemical structures, synthesis conditions, molecular weights of PGS prepolymers, and measurement techniques and conditions. The temperature of glass transition for cellulose is in the range of 200−250 °C.70,71 It can be seen from these results that Tα increases with the increasing content of CNCs initially and then decreases with a peak value at 7.15 vol %. With a CNC content lower than 7.15 vol %, the increasing trend of Tα is attributed to the limitation of the mobility of PGSU chains caused by stronger interactions with CNCs,72,73 in agreement with FTIR results. The decreasing trend of Tα with CNC content higher than 7.15 vol % can be interpreted by two factors. A higher content of CNCs may result in a lower cross-linking degree within PGSU due to the competition for the reaction with the isocyanate groups of HDI from the −OH groups on the surface of CNCs51,57 and, consequently, reduce Tα of PGSU.74 Moreover, the network structure of CNCs in PGSU may become poorer at the higher contents of CNCs, which can reduce the interface areas and weaken the interfacial interactions between PGSU and CNCs, thus, relieving the limitation on the mobility of PGSU chains. In the case of nanocomposites with lower contents (≤7.15 vol %), the stronger interfacial interactions prevail in comparison with the reduction in the cross-linking degree. Water-Responsive Mechanically Adaptive Properties. The softening effect of water on PGSU−CNC nanocomposites is investigated via DMA under isothermal conditions as a function of time at ambient temperature (24 °C), as shown in Figure 6a. The dry samples were tested for the first 10 min, after which, tests were continued with samples immersed in distilled water. It can be seen that PGSU does not exhibit detectable changes in its storage modulus, owing to its hydrophobicity. For PGSU−CNC nanocomposites, E′ starts decreasing upon wetting and reaches its equilibrium less than 20 min after immersion (t < 30 min), suggesting a relatively quick response rate75 to water under stretching. The nanocomposites with higher CNC contents reach their equilibrium slower than those with lower CNC contents. The reduction factors for modulus are 69, 74, 85, and 81% for PGSU3, PGSU4, PGSU5, and PGSU6, respectively.
The percolation model (eqs 7−9),66 which has been used to predict the reinforcement of CNCs in polymer nancomposites,29,39,40 is employed here to quantitatively analyze the change in Young’s modulus of PGSU−CNC nanocomposites and verify if CNCs indeed have formed a percolated network in the matrix. E=
with
(1 − 2ψ + ψ Φf )Ef Em + (1 − Φf )ψEf2 (1 − Φf )Ef + (Φf − ψ )Em
ψ=0
Φf < Φc
⎛ Φf − Φc ⎞0.4 ψ = Φf ⎜ ⎟ ⎝ 1 − Φc ⎠
Φf ≥ Φc
(7) (8)
(9)
Here, E, Ef, and Em are Young’s moduli of the composite, filler phase, and matrix, respectively. Φf is the volume percentage of filler in the composite, while Φc is the percolation threshold. Young’s modulus of the percolated network, that is, neat CNC films (Ef),28,29 was measured as 407 MPa in this case and Em = 1.09 MPa. Φc for CNCs is calculated by 0.7/A.67,68 A is the aspect ratio of CNCs and has a value of 11.8, as determined by SEM. Therefore, Φc for CNCs is 5.93 vol %. Figure 4c shows theoretical values predicted by the percolation model. It is evident from the data plots that the experimental moduli of PGSU−CNC nanocomposites above the percolation threshold match well with the values predicted by the percolation model. This suggests a percolation network indeed exists in these nanocomposites when their volume percentage is higher than 5.93 vol %, which accounts for the mechanical reinforcement, similar to those found in TPU−CNC nanocomposites.29,39 Dynamic Thermal Mechanical Properties. The temperature dependence of the storage modulus (E′) and loss factor (tan δ) of PGSU−CNC nanocomposites is shown in Figure 5. Figure 5a presents the evolution of E′ from the glassy region to glass/rubber transition region through to the rubbery region with respect to the increasing temperature. It can be seen that the reduction factor of E′ from the glassy region to rubbery region decreases with the content of CNCs, for example, 198 for neat PGSU, 21.3 for PGSU3, and 7.0 for PGSU6. This can
Figure 5. Dynamic mechanical analysis of PGSU-CNC nanocomposites: storage modulus (E′) (a) and loss factor (tan δ) (b). 2667
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Figure 7. Storage modulus (E′) as a function of time and exposure/ removal of water for PGSU−CNC nanocomposites. Water was removed at t = 30 min.
high-modulus CNC percolation network keeps the temporary shape fixed by counteracting the entropic recovery force of PGSU. Upon exposure to water, the CNC percolation network becomes softened, thus allowing the nanocomposite to recover its original shape as a result of the entropic recovery force from the elastomeric PGSU. Water-Active Shape-Memory Effects. Figure 8 shows the values of Rf and Rr for each nanocomposite for each cycle, which are two crucial parameters for the assessment of SMEs of a material. Neat PGSU is a hydrophobic elastomer, having no
Figure 6. Storage modulus (E′) (a) and swelling degree (b) as a function of water immersion time of PGSU−CNC nanocomposites at ambient temperature.
Figure 6b shows the swelling behaviors of PGSU−CNC nanocomposites in distilled water (at 22 °C) in parallel to DMA. The data show that all samples absorb water rapidly at the beginning of immersion and gradually level off at 20 min after immersion (t ≈ 30 min). The equilibrium swelling degree of neat PGSU is 3.8 wt %, in agreement with ∼4 wt % determined by Pereira et al. for immersion in phosphate buffered saline for 24 h.49 The equilibrium swelling degree increases with increasing content of CNCs, because of the hydrophilicity of CNCs. For instance, it increases to 17.4 wt % for PGSU6. By combining the modulus changing with the swelling behavior, it can be deduced that these two processes take place synchronously. Water plasticizes CNCs, breaking down strong hydrogen bonding between the CNCs and softens the percolated CNC network in the hydrophobic elastomer matrix. It is, however, noticeable that the modulus changing and the swelling degree do not reach their equilibrium synchronously; the former achieves equilibrium earlier than the latter. This might be caused by the periodic tensile load applied during the modulus-changing DMA test, which stretches the material and speeds up the process of water penetration, and by the small variation in ambient temperature. Figure 7 shows the modulus changing during the drying process after wetting. It can be seen that, for all nanocomposites, E′ starts to recover upon removal of water (t = 30 min) and gradually regains their high original value within 130 min (t < 160 min). It is noted that the results of this drying process are strongly influenced by sample dimensions, the drying condition and the material composition. The nanocomposites containing lower contents of CNCs absorb less water during water immersion and therefore their drying processes are faster than those with higher contents of CNCs. According to the mechanisms of water-active SMEs in elastomer-filler systems described in the Introduction, the rapid water absorption and the remarkable and reversible changes of modulus in response to water absorption/desorption are expected to render the PGSU−CNC nanocomposites SME effects. Wet PGSU−CNC nanocomposites are deformed and dried under force to generate a temporary distorted shape. The
Figure 8. Shape-memory properties of PGSU−CNC nanocomposites with distilled water as the stimulus at 22 °C (a, b) and with PBS (pH = 7.4) as the stimulus at 37 °C (c, d). 2668
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water-active SMEs. Rf values of PGSU are only around 10% for both stimuli (distilled water and PBS) caused by the plastic deformation during stretching. When water is used as the stimulus, Rf and Rr of the nanocomposites increase with the cycle number in the initial cycles and level off after three cycles (Figure 8a,b), which is presumably due to gradual elimination of the sample processing history76 and rearrangement of CNCs during stretching.23 This is similar to the cases in TPU−CNC nanocomposites,19,40 where prestretching is necessary for good and repeatable shape recovery. The Rf, once stable, increases with the content of CNCs from 72% for PGSU3 to 98% for PGSU6, while Rr increases from 95 to 99%. When the measurements were performed at body temperature (37 °C) using PBS as the stimulus to simulate body fluid conditions, Rf and Rr as a function of the cycle number of the nanocomposites are similar to those with distilled water as the stimulus and measured at 22 °C. The values of Rf and Rr for all the nanocomposite samples increase in the initial cycles and become relatively stable after several cycles. The final stable Rf and Rr increase with the increasing content of CNCs, reaching 98 and 99%, respectively, for PGSU6. The similarity in both sets of results involving either water or PBS as the stimulus indicates that the ionic strength of the medium has no substantial effect on the SME performance of PGSU−CNC nanocomposites. With these shape-memory performances, the PGSU−CNC nanocomposites have potential for use in bodyfluid responsive biomedical applications. Figure 9 demonstrates the SMEs of PGSU6 pretreated by two cycles of the wetting−stretching−drying process. The
Figure 10. Weight losses of PGSU and PGSU-CNC nanocomposite (PGSU6), incubated in enzyme-free and lipase enzyme-induced PBS solutions (pH = 7.4) in a shaker incubator (100 rpm) at 37 °C for up to 28 days.
time, respectively. These results indicate that the catalytic effect of the enzyme on hydrolytic degradation of the polymer49,77 is delayed in PGSU6 with the presence of CNCs. It is postulated that the enzymatic degradation of the ester groups from the PGS backbone in the PGSU is hindered by the formation of hydrogen bonds between the polymer and the CNCs, as well as by the barrier effects from CNCs.78,79 In comparison with TPU−CNC nanocomposites, the PGSU−CNC nanocomposites reported herein have a moderate water responsive rate, and higher/comparable Rf and Rr at similar filler contents. In this work, the final stable Rr and Rf values are 98 and 99% for the nanocomposite containing 23.2 vol % CNCs (PGSU6). Rf and Rr of the final cycle for TPU− CNC nanocomposites containing the same content of CNCs reported in the work of Zhu et al. are ∼95 and ∼95%.40 It is expected that by heating the nanocomposite at an elevated temperature, its water response rate will increase. Zhu et al.38 demonstrated that the wet TPU−CNC nanocomposites recovered their original modulus in about 20 min when heated up to and held at 75 °C. Different from conventional TPU, PGSU is a biodegradable elastomer.49 Thus, these PGSU− CNC nanocomposites with water-active SMEs will have potential in minimally invasive in vivo-degradable medical devices,1,41 such as body fluid-responsive surgical tools and selfdeployable medical devices. For example, the medical device may be packed and stored at dry state with the material at its fixed distorted shape before use. When inserted into the body, it responds to the body fluid and changes to the desired shape to exert its function.
Figure 9. Water-active shape-memory effects of pretreated PGSU6: the original shape (a, wet PGSU6 after immersed in distilled water for 1 h), the fixed deformed shape (b, dried PGSU6 after the wet PGSU6 was punched using a rod and distorted and subsequently dried at ambient temperature for 4 h), the deformed shape at the beginning of immersion in water (c), the recovered shape after a 1 h immersion in water (d), and the recovered shape after removal from water (e).
original shape of PGSU6 wetted in distilled water was a flat rectangle with a hole in the center (Figure 9a). The hole was distorted using a rod with a diameter larger than itself and dried at ambient temperature for 4 h. The deformed shape with a larger hole was obtained after the rod was removed from the film (Figure 9b). Finally, the deformed film was immersed in water again (Figure 9c), and the hole changed back to its original size after 1 h (Figure 9d,e), showing the water-induced shape-memory behavior and supporting the shape-memory results discussed above. In Vitro Degradation Behavior. Figure 10 presents the in vitro degradation behavior of PGSU and PGSU6 nanocomposite in enzyme-free and lipase enzyme-induced PBS solutions at 37 °C for up to 28 days under a dynamic condition. In the enzyme-free PBS solution, PGSU and PGSU6 specimens undergo similar weight losses of 7.7 and 8.4% in 28 days, while in lipase enzyme-induced PBS solution, both polymers exhibit enhanced weight losses of 27.0 and 17.5% in the same period of
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CONCLUSIONS We developed enzymatically degradable nanocomposites with water-active SMEs by using hydrophilic CNCs and hydrophobic poly(glycerol sebacate urethane). The presence of CNCs improved the tensile strength of PGSU, by up to 1040% for the PGSU-CNC nanocomposite containing 18.6 vol % CNCs, due to the strong interfacial interactions between CNCs and PGSU determined by FTIR. It also provided enhancements of Young’s modulus of PGSU, by up to 4400%, because of the formation of a strong percolation network of CNCs in the matrix, demonstrated by theoretical modeling. Furthermore, the elongation at break of all PGSU−CNC nanocomposites retained its high values at around 400%. Tα of PGSU determined by DMA was found to increase from −18.1 °C for neat PGSU up to −5.9 °C for the nanocomposite 2669
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containing 7.15 vol % CNCs, supporting the previous deduction of strong interfacial interactions. The modulus change triggered by water absorption or desorption was reversible and increased with increasing content of CNCs. This is because CNCs are hydrophilic and absorb an increasing amount of water at a higher content; the equilibrium water swelling degree increased from 3.8 wt % for neat PGSU to 17.4 wt % for the nanocomposite containing 23.2 vol % CNCs. As a result, the dry PGSU−CNC nanocomposites showed an increase of storage modulus by 120−470% compared to their wet counterparts. The incorporation of CNCs into PGSU endowed the PGSU−CNC nanocomposites with shape-memory effects. The shape fixity and shape recovery ratios became stable after the first three wetting−stretching−drying cycles, owing to the elimination of the sample processing history and alignment of CNCs. The stable shape fixity increased with increasing content of CNCs, from 72% in PGSU3 to 98% in PGSU6, while the shape recovery ratio maintains relatively high values, being 92− 99%, with either distilled water or PBS as the stimulus. In vitro degradation results showed the PGSU6 nanocomposite experienced a weight loss of 17.5% in 28 days in an enzymatic PBS condition, which is lower than that for neat PGSU but confirms hydrolytic degradability of the nanocomposite in the presence of an enzyme. This work provides an approach to the preparation of enzymatically degradable polymer nanocomposites with wateractive shape-memory effects and mechanically adaptive functions, which have potential in minimally invasive medical applications.
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AUTHOR INFORMATION
Corresponding Author
*E-mail: biqiong.chen@sheffield.ac.uk. Author Contributions †
These two authors contributed to the work equally (T.W. and M.F.). Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the Royal Society (Grant Number: RG120037), the University of Sheffield, and Irish Research Council for Science, Engineering and Technology for financial support.
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