Dual-Responsive Hydrogels for Direct-Write 3D Printing

Article pubs.acs.org/Macromolecules

Dual-Responsive Hydrogels for Direct-Write 3D Printing Musan Zhang,† Ankit Vora,*,† Wei Han,† Rudy J. Wojtecki,† Hareem Maune,*,† Alexander B. A. Le,† Leslie E. Thompson,† Gary M. McClelland,† Federico Ribet,† Amanda C. Engler,† and Alshakim Nelson*,†,‡ †

IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States Department of Chemistry, University of Washington, Seattle, Washington 98195, United States

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Downloaded by UNIV OF PENNSYLVANIA on August 31, 2015 | http://pubs.acs.org Publication Date (Web): August 31, 2015 | doi: 10.1021/acs.macromol.5b01550

S Supporting Information *

ABSTRACT: Direct-write 3D printing enables the fabrication of threedimensional objects via the extrusion from a nozzle. Stimuli responsive materials that shear-thin are well-suited as inks for these 3D printing systems. Poly(isopropyl glycidyl ether)-block-poly(ethylene oxide)-blockpoly(isopropyl glycidyl ether) ABA triblock copolymers were synthesized using controlled ring-opening polymerization to afford dual stimuliresponsive polymers that respond to both shear forces and temperature. These polymers were demonstrated to form hydrogels in water. The gels were observed to be thermoreversibledriven by the lower critical solution temperature of the poly(isopropyl glycidyl ether) block which helps facilitate loading of the ink into the printer syringe. Rheological studies demonstrated that the gels had a rapid and reversible modulus response to shear stress. Thus, these materials were suitable as inks for direct-write 3D printing, as they were easily extruded during printing and maintained sufficient mechanical integrity which was necessary to support the next printed layer. Printed structures of high aspect ratio pillars and stacked layers were successfully demonstrated. These types of 3D hydrogel structures may ultimately have an impact in the biomedical field for applications such as tissue engineering.

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INTRODUCTION Patterned hydrogels are of interest for a broad set of applications including drug delivery and tissue engineering.1−3 One emerging technology for patterning hydrogels is 3D printing, a form of additive manufacturing in which a threedimensional object is constructed one layer at a time. Although the engineering for 3D printers has matured since the 1980s, when it was first developed for industrial-scale rapid prototyping, there is an opportunity to explore new materials and expand the library of 3D printable inks.4 Furthermore, as 3D printing becomes more central to emerging biomedical technologies, there is also a need to create functional materials as inks.5−7 The ability to tune the chemical composition and tailor its thermal, rheological, and mechanical properties is also significant for adapting the material to existing 3D printers.8,9 These “drop-in” materials should conform to the current requirements for the inks used in these printers. Direct-write 3D printing is a method of 3D printing in which a syringe with a nozzle is rastered across a surface as it dispenses an ink. An ideal material for printing under ambient conditions (without thermal treatment as with traditional polymer extrusion) is a stimuli responsive material that responds to applied shear stress.10,11 A shear-thinning ink exists as a gel under ambient conditions but experiences a change in its viscosity as it is extruded through a nozzle and then immediately retains its shape after dispensation.12−14 Examples of shear-thinning inks include colloidal suspensions, waxes, polyelectrolyte gels, and hydrogels.15−17 The Lewis group reported the direct-write 3D printing of hydrogel © XXXX American Chemical Society

constructs using aqueous mixtures of Pluronic F127a commercially available ABA triblock copolymer of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO).18 In this case, the hydrogel is a temporary scaffold that can be removed afterward. Interestingly, these polymers possess a second stimulus response to temperature. The gels formed from F127 are thermoreversibledriven by the lower critical solution temperature (LCST) of the PPO block (∼20 °C). In a 25 wt % solution of F127, the polymers in water exist as soluble unimers at 5 °C and afford a viscous solution. However, as the temperature is increased, the solubility of PPO in water decreases which drives the formation of micelles comprised of a hydrophobic PPO core.19,20 The micelles pack into a facecentered-cubic structure in water resulting in a gel at 25 °C. Thus, these materials are dual stimuli-responsive. The shearthinning behavior of the gel enables the direct-write printing into 3D constructs. The thermoresponsive behavior of the gel is important for loading the ink into the syringe for the printer. Cooling the gel below the LCST of the PPO enables the fluid form of the mixture to be poured into the syringe of the printer in a very simple loading protocol. Furthermore, incorporation of heat sensitive drugs or hydrophobic additives can be easily formulated into a thermoresponsive ink.21 One challenge that exists for F127 is that the compositions available are not Received: July 13, 2015 Revised: August 20, 2015

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DOI: 10.1021/acs.macromol.5b01550 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

using polystyrene standards and a refractive index detector (1 mL/ min). UV−Vis Spectroscopy. UV measurements were performed on an 8453 UV−visible Measurement System. Temperature dependent absorbance measurements of all samples were performed at λ = 600 nm with measuring interval of 0.5 °C. The samples were dissolved and equilibrated at 5 °C in water to final concentrations of 0.5 wt %. Dynamic Light Scattering (DLS). Dynamic light scattering measurements were performed with a Malvern Zetasizer (Nano-ZS). The instrument was equipped with a He−Ne laser operating at 633 nm and an avalanche photodiode detector. A 0.5 wt % stock solution was prepared and allowed to fully dissolve and equilibrate at 5 °C. Serial dilutions were prepared of 0.1, 0.2, 0.3, and 0.4 wt % solutions, and the samples were passed through a 0.45 μm filter into low volume disposable cuvettes. The samples were heated in 5 °C increments from 5−35 °C and allowed to equilibrate for 10−20 min. Values obtained from DLS are presented as the average and standard deviation of at least three measurements. Polymer Synthesis. Triblock copolymers, PiPrGE-b-PEG-bPiPrGE, were polymerized in a glovebox. The following procedure for a 1.8−8.0−1.8k triblock serves as an example. Poly(ethylene glycol) (1 molar equiv, 10.0 g) was charged into a dry 100 mL roundbottomed flask, and toluene (33 mL) was subsequently added. The solution was heated and stirred until dissolved. Isopropylglycidyl ether (45 mol eq, 6.5 g) and tert-butyl-P4 catalyst (0.33 molar equiv/OH) was added was added, and the reaction was stirred at 45 °C for 8 h. Upon addition of the catalyst, the reaction turned yellow-orange. An aliquot was sampled at the end of the reaction to ensure no unreacted epoxide monomer remained. The solution was quenched with 3 mL of methanol and precipitated into diethyl ether. The polymer was collected via centrifugation (4.4 rpm, 4 °C, 10 min), and the supernatant was disposed. The polymer was redissolved in a minimal amount of dichloromethane and precipitated into diethyl ether (repeated twice). The polymer was redissolved into dichloromethane and passed through a 0.25 μm filter, concentrated, and dried at 40 °C under vacuum (10 mmHg). The 5, 10, and 15 wt % hydrogels were prepared by measuring the appropriate mass of polymer and dissolving it into deionized water at 5 °C for at least 2 days. NMR Measurement of the Spin−Lattice Relaxation Times (T1) To Approximate the Critical Micelle Concentration. T1 values were measured using the inverse recovery pulse sequence on a Bruker 300 MHz NMR spectrometer using D2O as the solvent at 300 K. Samples were serially diluted from a concentrated stock solution by the addition of D2O. Each sample was equilibrated for 10 min at reduced temperature (∼5 °C) upon mixing for the dilutions. This equilibration time was critical for these measurements as no trend was observed in T1 measurements if samples were prepared without equilibration. T1 values were calculated from the poly(ethylene glycol) resonance. The method approximating the critical micelle concentration (CMC) was based on a method developed by Lawson and Flautt29 where the CMC was observed at a maximum T1 value measured over a range of concentrations. Rheological Experiments. Dynamic oscillatory experiments were performed on a TA Instruments AR-2000ex equipped using a 25 mm parallel plate geometry. Samples, which were equilibrating in an ice bath for at least 10 min, were carefully loaded onto the Peltier plate at 5 °C. A preshear experiment was applied to ensure bubbles were eliminated from the sample cell, and a solvent trap was utilized to minimize solvent evaporation. The sample was equilibrated at 20 °C for 8 min. Strain sweep experiments were performed, and all experiments were conducted using a strain value in the linear viscoelastic regime. Temperature ramp experiments were performed at 1 Hz from 0−45 °C at 0.5 °C/min. Cyclic strain sweep experiments were conducted to investigate the shear-thinning and recovery behavior of the hydrogels. Samples were loaded on a 25 mm parallel plate geometry at 5 °C and a preshear experiment was performed to eliminate bubbles from the sample. Cyclic shear thinning tests (frequency 1 Hz) were performed at 20 °C using alternating strains of 1% for 2 min and 100% for 5 min per a cycle. Viscosity versus shear rate experiments were performed with a 40 mm cone and plate


suitable for addressing properties such as gelation temperature or the gel modulus. In particular, the gel modulus could potentially be important for applications related to tissue engineering, where the modulus can influence stem cell differentiation.22 Diblock (AB) and triblock (ABA) copolymers which possess at least one poly(alkyl glycidyl ether) block have been shown to form thermally responsive hydrogels as a consequence of the LCST behavior of the poly(alkyl glycidyl ether) block, although the shear-thinning behavior of these materials were not investigated.23−25 Herein, we report dual stimuli-responsive hydrogels comprised of poly(isopropyl glycidyl ether)-blockpoly(ethylene glycol)-block-poly(isopropyl glycidyl ether) (PiPrGE-b-PEG-b-PiPrGE) (Figure 1) for direct-write 3D

Figure 1. Chemical representations for F127 and PiPrGE-b-PEG-bPiPrGE triblock copolymers of this investigation which form thermoresponsive hydrogels. The pictures show a 15 wt % polymer 1 hydrogel at 5 and 20 °C in the sol and gel states, respectively.

printing. The polymers were synthesized via organocatalytic ring-opening polymerization of a glycidyl ether. The resulting polymers are similar to F127 in their thermal and shear response, but in contrast to F127, they possess thermoresponsive A blocks instead of the thermoresponsive B block present in F127. As a result, these polymers can form flowerlike micelles and bridged micelles in solvents selective for the B block,26 thereby promoting an extended and well-percolated physical network.27,28 The thermal and shear thinning behaviors of the polymer hydrogels were evaluated using rheology, and the results were correlated with the 3D printing of these materials using a direct-write 3D printer.

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EXPERIMENTAL SECTION

Materials and Instrumentation. Isopropyl glycidyl ether (iPrGE), poly(ethylene glycol) (PEG) (Mn 8000 g/mol), phosphazene base P4-t-Bu solution (0.8 M in hexane), and anhydrous toluene (99%) were purchased from Sigma-Aldrich. Pluronic F127 was purchased from BASF. Isopropylglycidyl ether was distilled from calcium hydride and stored under nitrogen. Poly(ethylene glycol) was dried twice azeotropically using toluene and further dried under vacuum for 2 d at 25 °C. 1H NMR Spectroscopy was performed on a Bruker Avance 400 MHz spectrometer, and referenced to residual solvent. Gel permeation chromatography was performed using a Waters chromatograph equipped with four 5 μm Waters columns (300 mm × 7.7 mm) connected in series with increasing pore size (10, 100, 1000, 105, 106 Å, using THF as the eluant, and calibrated with polystyrene standards (750−106 g/mol). Relative molecular weights were measured in THF B


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Macromolecules geometry at 25 °C. Gel yield stresses were measured under oscillatory stress (frequency 1 Hz, 25 °C) starting with an initial stress of 1 Pa. SEM Characterization of Hydrogel. SEM images were acquired on an FEI Helios Nanolab 400S FIB/SEM at 2.0 kV and 86pA. A 15 wt % gel of polymer 1 was freeze-dried, and the sample was coated with 5 nm carbon in a Cressington 208C evaporator. 3D Printing of Hydrogels. A direct-write printer was assembled from a three stepper motor stage which enabled the printer to translate in the x, y, and z directions at 10 μm resolution. The pressure was supplied using a Nordson fluid dispenser and the stepper motor stage was controlled by a Galil controller. The printer was controlled using a Matlab software. The 3D printable ink, which as a liquid at 5 °C, was poured into a Nordson Optimum 3 cc fluid dispensing barrel equipped with a conical (100 μm diameter) precision tip nozzle. The loaded barrel was capped and centrifuged at 4.4 rpm, 4 °C, and 5 min to eliminate any bubbles that were trapped during ink loading.


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RESULTS AND DISCUSSION Triblock copolymers of PiPrGE-b-PEG-b-PiPrGE were polymerized using anionic ring-opening polymerization with a tertbutylphosphazene catalyst.30−32 Two compositions with different outer block molecular weights were synthesized by varying the molar ratio of isopropyl glycidyl ether monomer to PEG macroinitiator. 1H NMR spectroscopy confirmed the monomers were completely consumed after 8 h of polymerization. Size exclusion chromatography (SEC) of the purified triblock copolymers displayed a monomodal shift to higher molecular weights compared to the PEG macroinitiator. The polymer composition was determined using the integration values of the ethylene oxide backbone (3.4−3.6 ppm) and the dimethyl protons at 1.15 ppm from the isopropyl glycidyl ether unit in the 1H NMR spectrum (see Supporting Information). The resulting Mn for polymers 1 and 2 were 1.8k-b-8.0k-b-1.8K g/ mol and 2.4k-b-8.0k-b-2.4K g/mol, respectively (Figure 1). The degree of polymerization was slightly less than the theoretical value suggesting there may have been homopolymer impurities in the initial crude product, which was removed after purification by precipitation.33,34 The self-assembly and micellization behavior of these block copolymers are dependent on both the solution concentration and temperature. In order to characterize the micellization process, a temperature-dependent UV−vis absorbance study and a concentration-dependent 1H NMR spectroscopic study were used to estimate the critical micelle temperature (CMT) and the critical micelle concentration (CMC), respectively. A temperature ramp experiment using UV−vis spectroscopy showed the CMT shifted from 28 to 22 °C as the size of the glycidyl ether block was increased (see Supporting Information). There are several established methods using NMR spectroscopy to evaluate a range of detailed information about the self-assembly of polymers into micelles in water.For instance, Lacelle and colleagues were able to extract the free energy, enthalpy, entropy of micellization as well as critical micelle temperatures and concentrations for a PEO−PPO− PEO triblock copolymer.35 Spin−lattice relaxation times (T1) obtained by 1H NMR spectroscopy determined that the approximate CMC at 27 °C for polymer 1 and polymer 2 were 0.8 and 0.22 wt %, respectively (Figure 2). We further investigated the sizes of the particles at various temperatures using dynamic light scattering (DLS) and compared these results to F127 controls of the same solution concentrations. It is important to note that unlike F127, polymers 1 and 2 showed scattering intensity curves that reflect several aggregate size populations within the temperature range

Figure 2. 1H NMR T1 study for the approximation of critical micelle concentration (CMC) of polymers 1 and 2 in D2O at 27 °C.

tested. In contrast, F127 displayed two separate aggregate sizes at ∼9 and ∼45 nm below 35 °C, which eventually converged into a single peak of ∼25 nm at higher temperatures (see Supporting Information). This behavior for F127 in water is attributed to the unimer to core−shell micelle transition.19,36 For polymers that form flower-like micelles, the solution structures are more complex and may not display a welldefined, one-step unimer-to-micelle transition since several mechanisms can occur simultaneously leading to a distribution of multiple aggregate populations.37 We investigated the relationship between hydrodynamic diameter size as a function of temperature using DLS (see Supporting Information). Polymer 2, with a larger molecular weight hydrophobic block, displayed an inflection point and increase in the hydrodynamic diameter between 10 and 15 °C. In contrast, polymer 1 showed a broader temperature inflection point that was highly dependent on the solution concentration. The results demonstrate that the micellization temperature is dictated by hydrophobic interactions, which are tuned by the molecular weight of the hydrophobic outer block and the polymer concentration. At polymer concentrations above 15 and 10 wt %, polymers 1 and 2 formed room temperature hydrogels, respectively (see Supporting Information). The mechanical and thermoresponsive behavior of the hydrogels at varying weight percentages in water were further probed using rheology. Figure 3 compares the dynamic elastic (G′) and viscous (G″) moduli for 15 wt % concentrations of polymers 1 and 2, as well as a 20 wt % solution of F127. These hydrogels all displayed thermoresponsive gelation below room temperature. As shown in Table 1, polymers 1 and 2 have gelation temperatures (Tgel(G′ = G″)), at 14.3 and 9.5 °C, respectively. Both polymers 1 and 2 have a lower Tgel compared to F127 (Tgel = 34 °C) at 15 wt % concentrations suggesting the polymer triblock structure and composition play a significant role in determining the mechanical properties of the hydrogels. Furthermore, the hydrogels derived from polymers 1 and 2 demonstrated a higher gel modulus compared to F127 at identical hydrogel weight percentages. Polymers 1 and 2 at 15 wt % have G′ (T = 25 °C) values of 20.6 and 24.5 kPa, respectively, compared to a 15 wt % F127 solution, which remains a liquid. In order to obtain comparable room temperature G′ values of F127, a C


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Figure 3. Dynamic oscillatory temperature ramp experiments showing storage (solid) and loss (dash) moduli for 20 wt % F127 (green), 15 wt % polymer 1 (red), and 15 wt % polymer 2 (blue) hydrogels.

Table 1. Summary of Gel Point Temperatures and Storage Moduli (G′) at 25 °C at Varying Weight Percentage Concentration Hydrogels of Polymer 1, 2, and F127 composition

wt % gel

gel point tempa,b (°C)

G′ (T = 25 °C)b (kPa)

polymer 1

10 15 10 15 15 20 30

37.0 14.3 21.6 9.5 34.4 17.2 10.3

1.6 20.6 16.0 24.5 liquid 15.1 35.0

polymer 2 F127

Figure 4. Temperature−concentration phase diagrams summarizing the solution and hydrogel properties of polymers (a) 1 and (b) 2.

a

Gel point identified as G′ = G″ during a temperature sweep. b Determined by rheology.

which has larger isopropyl glycidyl ether blocks, also existed as a free-flowing solution across all temperatures at 1 wt %. At 5 wt % concentration of polymer 2, the mixture was a clear liquid at 5 and 10 °C. At 15 °C, the solution became more viscous, and above 20 °C, the solution remained an opaque gel. The 10 wt % concentration of polymer 2 afforded a gel across all of the temperatures tested above 10 °C. The polymer persisted only as a transparent gel when the concentration was increased to 15 wt % at all temperatures above 5 °C. Interestingly, most of the solutions and gels derived from polymer 2 possessed an opaque appearance. We attribute this phenomenon to the presence of larger assemblies of polymer 2 relative to polymer 1. These polymers are expected to form flower micelles in water that can also form aggregates of flower micelles bridged by polymer chains that span two micelles. Investigations are currently being conducted to elucidate the morphologies of the structures being formed in solution. The SEM images of lyophilized hydrogels showed porous, mesh-like morphology (Figure 5). Similar porous morphologies were observed in SEM images of other injectable supramolecular hydrogels.38 An ideal material for extrusion through a small diameter nozzle in direct-write 3D printing is a shear-thinning polymer ink. Therefore, we investigated the shear-thinning behavior and the gel yield stress at 25 °C. Figure 6 shows the three gels obtained from F127, polymer 1 and 2 have linearly decreasing shear viscosities as the shear rate increases. The viscosity versus shear rate trend increased from 20 wt % F127 to 15 wt % polymer 1, and 15 wt % polymer 2 as expected based on the storage moduli of the gels at room temperature. These results indicate the gels are non-Newtonian fluids and shear-thinning.

higher weight percent gel was necessary. For example, a 20 wt % solution of F127 has a G′ (T = 25 °C) of 15.1 kPa. Our results suggest that the gelation mechanism and mechanical structure of the hydrogels derived from polymers 1 and 2 are dictated by the composition and block architecture of the polymers that drive the formation of flower micelles in solution. The PiPrGE-b-PEG-b-PiPrGE triblock structure demonstrated improved mechanical properties compared to F127 and formed hydrogels at lower concentrations. Furthermore, the lower gelation temperatures of polymers 1 and 2 reduced the potential variability in the gel mechanical properties which enabled more consistent printing at room temperatures. In contrast, a 20 wt % F127 hydrogel, which exhibited a gel point at 17.2 °C may encounter more variabilities with small room temperature fluctuations. The physical network of our gels reached the percolation threshold at lower concentrations and temperatures compared to F127. This result is attributed to both the physical entanglements and reinforcing bridged loops between micelles. Temperature−concentration phase diagrams were constructed to summarize the physical properties of the polymer solutions at temperatures ranging from 5 to 50 °C and concentrations between 1 and 15 wt %. As shown in Figure 4, polymer 1 in water remained as a clear solution from 5 to 50 °C at 1 and 5 wt % concentrations. At 10 wt %, the aqueous mixture remained as a clear solution from 5 to 20 °C, but became viscous as the temperature increased up to 35 °C. At 40 °C, the mixture became an opaque gel. At 15 wt %, the gelation temperature of polymer 1 decreased to ∼10 °C and remained as a transparent gel at the higher temperatures. Polymer 2, D


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Figure 7. Storage modulus versus stress showing the corresponding yield stress for 20 wt % F127, 15 wt % polymer 1, and 15 wt % polymer 2.

Figure 5. SEM micrographs of 15 wt % polymer 1 hydrogel showing three-dimensional porous network.

Figure 8. Cyclic shear-thinning experiment of 15 wt % polymers 1 and 2 and 20 wt % F127 gels showing G′, storage modulus, response and instantaneous recovery to high (100%) and low (1%) oscillatory strains. Red, blue, and green lines show storage modulus for polymers 1, 2, and F127 respectively, and the dotted line represents the corresponding strain applied to the gel. Figure 6. Viscosity versus shear rate profile of 20 wt % F127, 15 wt % polymer 1, and 15 wt % polymer 2 at 25 °C showing non-Newtonian behavior and shear-thinning properties.

hydrogels from F127 were subjected to four cycles of low (1%) and high (100%) strains for 2 and 5 min, respectively. All the hydrogels exhibited a marked decrease in the G′ moduli at high strains and immediate recovery at low strains for each cyclic testing. F127, the weakest gel, had G′ moduli of ∼1.5 and 0.004 kPa at 1% and 100% strains, respectively. Polymer 1 had G′ moduli of ∼7 kPa and ∼0.14 kPa at 1% and 100% strains, respectively. Polymer 2, being a stronger gel, had G′ moduli of ∼10 kPa and ∼0.7 kPa at 1% and 100% strains, respectively. Polymer 2, having larger isopropyl glycidyl ether blocks, had stronger hydrophobic interactions, which afforded a higher G′ even at higher strains. All the hydrogels demonstrated the G′ response to high and low strains occurred in less than 15 s. This rapid and reversible shear-thinning behavior is attributed to the disruption of the physical network under large shear deformations while the recovery was due to the rapid reformation of the transient network, which was promoted by hydrophobic interaction.14 Furthermore, our hydrogels displayed minimal mechanical hysteresis between strain cycles, a desirable property for direct-write 3D printing. The small degree of hysteresis between the first and second cycles was likely due to the initial equilibration at 0% strain for 8 min leading to the observed higher G′ in the first cycle. This rapid and reversible modulus response to shear stress renders these

We further investigated the gel yield stress, an important parameter that implies the force necessary for gel extrusion. The gel yield stress also provides an indirect indication of the gel strength as it supports subsequent stacked layers during 3D printing. In other words, a gel with a higher yield stress will be capable of supporting more stacked layers without printing defects such as sagging than a gel with a low yield stress. Figure 7 suggests that the combination of composition and architecture of polymers 1 and 2 contributed not only to the increased storage moduli, but also significantly increased the yield stress relative to F127. Hydrogels of polymers 1 and 2 at 15 wt % afforded a yield stress of 0.72 and 3.47 kPa, respectively, compared to 0.85 kPa for the F127 gel at 20 wt %. These results strongly suggest that polymers 1 and 2 will have a better printing performance and enhanced printing quality than F127. The reversible (and self-healing) nature of the physical crosslinks that exist within these hydrogel networks manifests itself in the instantaneous response of the gel modulus to changes in the applied strain as illustrated in Figure 8. In this experiment, 15 wt % hydrogels derived from polymer 1 and 2 and 20 wt % E


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Figure 9. 3D printed structures: (a) unsuccessful pillar printing using 23 wt % F127, (b) successful printing of 14 wt % polymer 2 pillar, and (c) eight-layered stacked structure using 14 wt % polymer 2 and (d) a depiction of a direct-write printer showing layer-by-layer ink deposition. Free standing pillar height was ∼2400 μm and all structures were printed from a direct-write printer with a 100-μm diameter nozzle (scale bar 1 mm).

(glycidyl ether) triblock copolymers were synthesized using a controlled ring-opening polymerization, and the corresponding hydrogels were investigated for direct-write 3D printing. Similar to F127, these polymers were dual stimuli-responsivehaving both a temperature and shear response. However, the resulting hydrogels also proved to have a higher gel modulus and yield stress when compared to F127 hydrogels. These parameters are important for printing hydrogel constructs that are able to withstand its own weight, and an 8-layer stack of “IBM” was printed without the structure losing its shape or flattening over time. We expect that the versatility of the synthetic approach will enable the formation of functional structures that may serve as interesting materials for tissue engineering scaffolds and other biomaterial applications.

materials suitable as inks for direct-write 3D printing because they can be easily extruded during printing while maintaining sufficient mechanical integrity necessary to support the next printed layer. We demonstrated the ability to 3D print the hydrogels into free-standing patterned structures. The hydrogel inks were transferred into the printer syringe by cooling the gel to 5 °C and pouring the solution. Upon warming to ambient temperature, the ink became a gel which could be printed via extrusion through a 100 μm diameter nozzle. Figure 9 shows that the 3D printing of pillar structures (aspect ratio ∼21) was successful using 14 wt % polymer 2 but not for 23 wt % F127. The ability to print these high aspect ratio features was attributed to the enhanced gel properties arising from the composition and block architecture of our polymers that afforded a higher gel yield stress for polymer 2, which was 2 orders of magnitude greater compared to F127 (Figure 7). Additionally, we were able to 3D print “IBM” comprised of eight stacked layers. The printed structures exhibited good resolution (∼100 μm line width), and the printedlayers showed adequate structural consistency throughout printing. The width of the printed features corresponded to the nozzle diameter and exhibited good structural integrity. Printing defects such as buckling and sagging of the stacked structures were not observed in our materials, which was attributed to the superior gel mechanical properties.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.5b01550. Details of characterization methods, dynamic light scattering, results, and rheological characterization (PDF)

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AUTHOR INFORMATION

Corresponding Authors

CONCLUSION Additive manufacturing, including 3D printing is rapidly becoming a viable technology which will require materials innovations to meet the emerging demands. While F127 based hydrogels are commercially available and useful for direct-write 3D printing, these materials are limited in some of their properties, such as modulus and yield stress, which would enable the printing of more complex 3D structures. Poly-

*(A.V.) E-mail [email protected]. *(H.M.) E-mail [email protected]. *(A.N.) E-mail [email protected]. Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. F


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Macromolecules Notes

(30) Misaka, H.; Tamura, E.; Makiguchi, K.; Kamoshida, K.; Sakai, R.; Satoh, T.; Kakuchi, T. J. Polym. Sci., Part A: Polym. Chem. 2012, 50 (10), 1941−1952. (31) Isono, T.; Satoh, Y.; Miyachi, K.; Chen, Y.; Sato, S.; Tajima, K.; Satoh, T.; Kakuchi, T. Macromolecules 2014, 47 (9), 2853−2863. (32) Zhao, J.; Pahovnik, D.; Gnanou, Y.; Hadjichristidis, N. Macromolecules 2014, 47 (5), 1693−1698. (33) Zhao, J.; Mountrichas, G.; Zhang, G.; Pispas, S. Macromolecules 2009, 42 (22), 8661−8668. (34) Zhao, J.; Mountrichas, G.; Zhang, G.; Pispas, S. Macromolecules 2010, 43 (4), 1771−1777. (35) Cau, F.; Lacelle, S. Macromolecules 1996, 29 (1), 170−178. (36) Mortensen, K.; Pedersen, J. S. Macromolecules 1993, 26 (4), 805−812. (37) Mortensen, K. Macromolecules 1997, 30 (3), 503−507. (38) Tan, H.; Xiao, C.; Sun, J.; Xiong, D.; Hu, X. Chem. Commun. 2012, 48 (83), 10289−10291.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors acknowledge IBM for funding support. REFERENCES

(1) Peppas, N. A.; Hilt, J. Z.; Khademhosseini, A.; Langer, R. Adv. Mater. 2006, 18 (11), 1345−1360. (2) Polizzotti, B. D.; Fairbanks, B. D.; Anseth, K. S. Biomacromolecules 2008, 9 (4), 1084−1087. (3) Guillame-Gentil, O.; Semenov, O.; Roca, A. S.; Groth, T.; Zahn, R.; Vörös, J.; Zenobi-Wong, M. Adv. Mater. 2010, 22 (48), 5443− 5462. (4) Lipson, H.; Kurman, M. Fabricated: The new world of 3D printing; John Wiley & Sons: New York, 2013. (5) Lewis, J. a. Adv. Funct. Mater. 2006, 16, 2193−2204. (6) Calvert, P. Chem. Mater. 2001, 13, 3299−3305. (7) Schultz, A. R.; Lambert, P. M.; Chartrain, N. A.; Ruohoniemi, D. M.; Zhang, Z.; Jangu, C.; Zhang, M.; Williams, C. B.; Long, T. E. ACS Macro Lett. 2014, 3 (11), 1205−1209. (8) Tumbleston, J. R.; Shirvanyants, D.; Ermoshkin, N.; Janusziewicz, R.; Johnson, A. R.; Kelly, D.; Chen, K.; Pinschmidt, R.; Rolland, J. P.; Ermoshkin, A.; Samulski, E. T.; DeSimone, J. M. Science 2015, 347 (6228), 1349−1352. (9) Hofmann, M. ACS Macro Lett. 2014, 3 (4), 382−386. (10) Guvendiren, M.; Lu, H. D.; Burdick, J. A. Soft Matter 2012, 8 (2), 260−272. (11) Peterson, G. I.; Larsen, M. B.; Ganter, M. A.; Storti, D. W.; Boydston, A. J. ACS Appl. Mater. Interfaces 2015, 7, 577−583. (12) Pawar, G. M.; Koenigs, M.; Fahimi, Z.; Cox, M.; Voets, I. K.; Wyss, H. M.; Sijbesma, R. P. Biomacromolecules 2012, 13 (12), 3966− 3976. (13) Butler, P. Curr. Opin. Colloid Interface Sci. 1999, 4 (3), 214−221. (14) Winnik, M. A.; Yekta, A. Curr. Opin. Colloid Interface Sci. 1997, 2, 424−436. (15) Lewis, J. A.; Gratson, G. M. Mater. Today 2004, 7 (7−8), 32− 39. (16) Lewis, J. A. Curr. Opin. Solid State Mater. Sci. 2002, 6 (3), 245− 250. (17) Hansen, C. J.; Saksena, R.; Kolesky, D. B.; Vericella, J. J.; Kranz, S. J.; Muldowney, G. P.; Christensen, K. T.; Lewis, J. a. Adv. Mater. 2013, 25, 96−102. (18) Kolesky, D. B.; Truby, R. L.; Gladman, a. S.; Busbee, T. a.; Homan, K. a.; Lewis, J. a. Adv. Mater. 2014, 26, 3124−3130. (19) Mortensen, K. J. Phys.: Condens. Matter 1996, 8, A103−A124. (20) Mortensen, K.; Talmon, Y. Macromolecules 1995, 28, 8829− 8834. (21) Jones, M.-C.; Leroux, J.-C. Eur. J. Pharm. Biopharm. 1999, 48 (2), 101−111. (22) Engler, A. J.; Sen, S.; Sweeney, H. L.; Discher, D. E. Cell 2006, 126, 677−689. (23) Ogura, M.; Tokuda, H.; Imabayashi, S.; Watanabe, M. Langmuir 2007, 23 (18), 9429−9434. (24) Labbé, A.; Carlotti, S.; Deffieux, A.; Hirao, A. Macromol. Symp. 2007, 249−250, 392−397. (25) Lee, B. F.; Kade, M. J.; Chute, J. a.; Gupta, N.; Campos, L. M.; Fredrickson, G. H.; Kramer, E. J.; Lynd, N. a.; Hawker, C. J. J. Polym. Sci., Part A: Polym. Chem. 2011, 49 (20), 4498−4504. (26) Yang, J.; Zheng, X.; Zhang, B.; Fu, R.; Chen, X. Macromolecules 2011, 44 (4), 1026−1033. (27) Zhou, Z.; Chu, B.; Nace, V. M.; Yang, Y.-W.; Booth, C. Macromolecules 1996, 29 (10), 3663−3664. (28) Liu, T.; Zhou, Z.; Wu, C.; Chu, B.; Schneider, D. K.; Nace, V. M. J. Phys. Chem. B 1997, 101 (43), 8808−8815. (29) Lawson, K. D.; Flautt, T. J. J. Phys. Chem. 1965, 69 (9), 3204− 3205. G


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