Highly Stretchable and Instantly Recoverable Slide-Ring Gels

Publication Date (Web): July 17, 2018. Copyright © 2018 American Chemical ... Chemistry of Materials. Cao, Huang, Chang, and Cheng. 0 (0),. Abstract:...
0 downloads 0 Views 1MB Size
Subscriber access provided by Kaohsiung Medical University

Article

Highly Stretchable and Instantly Recoverable Slide-Ring Gels Consisting of Enzymatically Synthesized Polyrotaxane with Low Host Coverage Lan Jiang, Chang Liu, Koichi Mayumi, Kazuaki Kato, Hideaki Yokoyama, and Kohzo Ito Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.8b01208 • Publication Date (Web): 17 Jul 2018 Downloaded from http://pubs.acs.org on July 29, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials

Highly Stretchable and Instantly Recoverable Slidelide-Ring Gels ConsistConsisting of Enzymatically Synthesized Polyrotaxane with Low Host Coveroverage Lan Jiang1*, Chang Liu1, Koichi Mayumi1, Kazuaki Kato1, 2, Hideaki Yokoyama1 and Kohzo Ito1* 1Department

of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan. 2Research Center for Structural Materials, National Institute for Materials Science, 1-2-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan. ABSTRACT: Gels with high mechanical performance have attracted great interests because of their potential biomedical applications. Tough gels reported thus far usually contain sacrificial species to dissipate energy, and thus compromising the fatigue resistance. In this study, highly stretchable and recoverable gels can be achieved by crosslinking cyclodextrin (CD)based polyrotaxane with a low host coverage, synthesized via a one-pot enzymatic end-capping reaction with 90% yield and ~2% CD coverage (PR02). The low coverage allows the CD cross-links to freely slip on the axis over large distance (~2/3 of the axis length), and thus, allows the PR02 slide-ring network keep intact under large deformation via pulley effect. The PR02 hydrogel can be stretched up to ~1600% long, withstand ~1 MPa stress, and fully recover instantly. PR02 DMSO gels exhibit a shape memory behavior withstood large deformation. As the first research to control the final property of the network by precisely controlling the slide distance of the cross-links, this work not only push the performance envelope of soft matters, but also opens new opportunities for designing tough materials.

Introduction Gels are three-dimensional polymer networks containing large amount of solvent, which have great potential to be utilized in tissue engineering,1 drug delivery,2 actuators3 and so on. Practical applications of gels, however, are restricted because of their low mechanical strength, which is a result of the inhomogeneous structure created by crosslinking.4 One common strategy to improve the strength of gels is through the dissipation of energy under deformation, e.g. double-network hydrogels5-6, dual-crosslinked hydrogel7-8 or nanocomposite gels.9-10 Although energydissipating gels can provide remarkable stress or stretchability, they generally cannot recover to their initial state instantly in loading-unloading processes, and exhibit large hysteresis loops even after small deformations, owing to the permanent rupture of the network. Some efforts were achieved by introducing reversible sacrifice bonds11-12 or nanoparticles13-14 in the system, but the gel recovery was still time-consuming and only functioned for relatively small deformations and strains, which poses great obstacle to applications such as artificial cartilage or force sensors that required both stretchability and recoverability. Currently, tough gels with high fatigue resistance that can withstand consecutive, high-level loading-unloading processes are still long-pursued yet largely unmet. “Slide-ring gel”,15 a typical “slide-ring material”16 based on polyrotaxane (PR), can provide a peculiar mechanical property which is different from conventional chemical, physical or multicomponent gels. PR is a mechanically interlocked molecule composed of a linear polymer guest

(polyethylene glycol (PEG)) threaded into multiple cyclic molecule hosts (cyclodextrin (CD)). “Slide-ring materials” can be formed by using the CD hosts as crosslinking points in various structural materials such as hydrogels,17 elastomers18, silica aerogels19 and silicon anode binders.20 As the CD cross-links are able to slip on the polymer axis between adjacent CDs, the inhomogeneous structure can be adjusted to some extent, and the tension in the network can be equalized in a manner similar to that in case of pulleys (Scheme 1a). Thus, the slide-ring gels seems to have potential to provide good mechanical properties without compromising recoverability. Unfortunately, the reported slide-ring gels can only work well in low strength (stress at break only several tens kPa),17, 21 which is far below the level that energy-dissipating gels can achieve (~MPa). We think it is probably because the slidable range of the crosslinks is limited in the products reported thus far. The commonly used CD-based PR composed of PEG (Mw=1040k) usually exhibit 25-30% CD coverage (percent ratio of covered length of axis polymer chain), large number of free CDs remain on the strand after gelation, which greatly limits the slipping of the cross-links and causes the failure of the network (Scheme 1b). As the pulley effect plays a key role in slide-ring gel, making the cross-links slip over large distance may be of vital importance to develop the full potential of the pulley effect, so as to obtain gels with a high strength, toughness and recoverability.

ACS Paragon Plus Environment

Chemistry of Materials 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Scheme 1. (a) Pulley effect; (b) High-covered polyrotaxanes are easily to undergo crack propagation; (c) Low-covered polyrotaxanes can withstand large tension, possess good stretchability and recoverability stemmed from the wide slidable range for cross-links. Based on the interlocked structure of the PR, decreasing the number of cyclic hosts21 is expected to be a promising way to make CD cross-links slip over large distance on the polymer axis without obstacles (Scheme 1c). However, it has been difficult to control the host-guest stoichiometry effectively thus far. Conventional synthese of PR always require complicated steps with a series of solvent changes22-23or strict conditions with toxic catalysts24-27, and the yield greatly shrinks when attempting to control over the CD coverage.21, 28-29. In this study, a CD-based PR with very low CD coverage (~2%) is successfully obtained via a one-pot enzymatic end-capping reaction in very high yield (>90%) for the first time. It is found that the 2% covered PR hydrogel can be stretched ~16 times in length with ~1 MPa stress, which is almost the best mechanical properties for reported chemical single-network hydrogel without energy dissipation and even comparable to some energydissipating gels, but still instantly recoverable. As the PEG axis in the low covered PR are almost exposed without the shelter of CDs, the corresponding DMSO gel exhibits a shape memory behavior in large deformation, due to the synergy of the slide-ring effect and orientation-induced PEG crystallization. The mechanism of the improvement is also investigated in this work via comparing with the properties of the hydrogels based on 25% covered PR and poly(vinyl alcohol) (PVA). It is proved that by decreasing of the host coverage from 25% to 2%, the slide range of the CD cross-links is increased from 18% to 65% of the axis length in the corresponding gels, so the polymer strands in the network can be fully utilized under large deformation. This work not only provides a new strategy to obtain recoverable gels with good mechanical performance, but also opens new opportunities for designing tough materials. Experimental Section Materials. All reagents were used as received. The Microbial Transglutaminase was provided by Ajinomoto Co. (Tokyo, Japan), The (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD, hydroxylpropyl modification degree ~37.7%), N-α-carbobenzoxy-L-glutaminyl-glycine (Z-Gln-Gly), divinyl sulfone (DVS), Glutaraldehyde (GA), poly vinyl alcohol (PVA, Mn=31000) and N,N'-carbonyldiimidazole (CDI)

were purchased from Sigma-Aldrich. The Phosphate Buffer solution (PBS, 0.1mol/L, pH8.0) was purchased from Wako. The amino-terminated PEG (PEG-NH2, Mw=10000, 20000, 30000) was purchased from NOF corporation. The 25% CD covered PR was purchased from Advanced softmaterials Inc. (PEG axis Mw=35000, CD coverage ~24.2%, hydroxylpropyl modification degree ~52%, denoted as PR25 (Figure S1)). The synthesis of the 2% covered PR polyrotaxane. The HP-α-CD (1 g) was dissolved in 3 mL PBS (0.1 mol/L, pH 8.0), then PEG-NH2 (0.2 g) was added and stirred to get the clear solution. The mixture was stood in 4℃ for 36 h, then Z-Gln-Gly (0.08 g) and TGase (10 mg) were added into the mixture for end-capping. The reaction stirred at room temperature for 3 days. Then, the mixture was dialyzed (MWCO: 12000-14000) to remove the free CD and Z-GlnGly. After freeze drying, the rough product was washed by THF to remove free PEG, and then dialyzed again. The dialyzed solution was filtrated via 0.45 μm filter paper, and then freeze dried to obtain the final product. The preparation of the PR hydrogel. PR was dissolved in 0.01 M NaOH with different weight concentration. The DVS was added to the solution of PR in different weight concentration to obtain pre-gel solutions. These pre-gel solutions were cross-linked at room temperature for 24 h in a 1 mm thickness Teflon mould. The obtained gels were removed from the mould, and the edges were cut off to obtain rectangular gels for the tensile measurements. The resulting PR hydrogels named “x%PR02/25-y%DVShydrogel” (x refers to the PR concentration, and y refers to the DVS concentration (wt%)). The preparation of the PVA hydrogel. PVA was dissolved in water with 16 wt%. The 1 M HCl solution (3.5 wt%) and GA in different weight concentration was added to the solution to obtain pre-gel solution. These pre-gel solutions were cross-linked at room temperature for 24 h in a 1 mm thickness Teflon mould. The obtained gels were removed from the mould and the edges were cut off to obtain rectangular gels for the tensile measurements. The resulting PVA hydrogels named “x%PVA-y%GA-hydrogel” (x refers to the PVA concentration, and y refers to the crosslinker concentration (wt%)). The preparation of the PR DMSO gel. PR was dissolved in anhydrous DMSO in 16 wt%. The CDI was added to the solution to obtain pre-gel solution. The pre-gel solutions were cross-linked at 60℃ overnight in a 1 mm thickness Teflon mould. The obtained gels were removed from the mould and the edges were cut off to obtain rectangular gels. The resulting DMSO gels named “x%PR02/25-y%CDIDMSO gel” (x refers to the PR concentration, and y refers to the crosslinker concentration (wt%)). Characterization NMR spectroscopy, 1H-NMR spectra were recorded at 400 MHz on a JEOL JNM-AL400 spectrometer, under temperatures of 343 K in d6-DMSO solvent. ATR-Fourier transform infrared spectroscopy, ATRFourier transform infrared spectra were recorded in air using a NICOLETis50 Spectrometer (Thermo Electron Co., Ltd.), where the samples were directly measured under a DuraSamplIR II diamond ATR accessory.

ACS Paragon Plus Environment

Page 2 of 9

Page 3 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials Small-angle X-ray scattering (SAXS) for 2% covered PR solution (0.5 wt% in 0.01M NaOH) was done at beam line BL-05SS at SPring-8 (Hyogo, Japan) for obtaining the gyration radius. The sample-to-detector distance was 3863 mm and the 2D SAXS patterns were recorded with a PILATUS 1M system (Dectris). The exposure time was 10.0 s. In Figure S2 we present the SAXS profile of 0.5 wt% 2% covered PR solution and its fitting results using Debye equation (Eq. S1). The gyration radius of 2% covered PR Gaussian chain Rg was calculated as 13.3 nm. The tensile tests were carried out at 25℃ on a Shimadzu EZ-S universal tester with a 5 N load cell. For uniaxial tensile tests, 18×3×1 mm3-sized samples were stretched till failure at 60 mm/min deformation rate. For loading-unloading tests, 7×3×1 mm3-sized samples were placed into a humidity-controlled chamber (Figure S3) and loaded for 100 cycles without stop at 250 mm/min deformation rate. For stress relaxation tests, a 7×3×1 mm3-sized sample was loaded to extension ratio λ =2, 4, and 7 in sequence. Between each step, the sample was held for 10 minutes. The stress was recorded as a function of time t. To minimize dehydration during the fatigue and relaxation tests, we made a simplified humidity chamber30 (Figure S3). A humidifier provided continuous water vapor into the chamber. The samples were weighted before and after tests, and found less than 5% weight loss. The fracture tests were also carried out at 25℃ on a Shimadzu EZ-S universal tester with a 5 N load cell. A 2mm length initial crack was introduced to the middle point of the vertical boundary of a 25×10×1 mm3-sized “single edge notched tensile” (SENT) specimen by a sharp blade (Figure S4a). Stress-Extension ratio curves of notched and un-notched samples were both obtained at 60 mm/min strain rate. The extension ratio for the initial crack to start propagation was considered to be the critical extension ratio of fracture εc. The fracture energy Γ was calculated as:   2 

 

(eq. 1) (eq. 2)

where k is a parameter related to critical extension ratio, A the strain energy density which could be deduced from the area covered by the un-notched specimen StressExtension ratio curve from 1 to εc, and c is the initial crack length (Figure S4b). Wide-angle X-ray scattering (WAXS). Synchrotron wide-angle X-ray scattering measurements were conducted at beam line BL-05SS at SPring-8 (Hyogo, Japan). The wavelength of the incident X-ray beam was 1 Å, and the beam size was 0.1 mm (vertical) × 0.2 mm (horizontal). The sample-to-detector distance was 64 mm and a CMOS flatpanel detector from Hamamatsu Photonics (C9728DK) was used as the 2D detector. Opaque gels are stepwisely heated from room temperature to 50 ℃ by a LINKAM TST350 tensile hot stage. The sample is soaked at the desired temperature for 2 min and then exposed to X-ray for 5 s to collect the scattering profile. Results and discussion

Synthesis and characterization of the polyrotaxane with low cyclodextrin coverage. The synthesis of CDbased PR generally has two key points: the formation of pseudopolyrotaxane (PPR) and the end-capping reaction. Since hydrogen bonds between the native CDs play the primary role in the formation of common PPRs, native CDs tend to aggregate along the main chain and form a channel-like structure,31 making it difficult to control the hostguest stoichiometry effectively. In this work, the hydroxylpropyl α-CD was used as the host instead of native α-CD, to avoid hydrogen bonds between adjacent CDs and minimize the CD number on the PR. For the end-capping step, an enzymatic end-capping reaction was established for the first time in this work, by using microbial transglutaminase (mTGase) as the catalyst and dipeptide Z-Gln-Gly as the end group. The mTGase is stable and expresses enzymatic activity over wide pH (pH 4-9) and temperature range (450℃)32 in aqueous solution, and thus a high-yield synthesis protocol of PR can be established.

Scheme 2. The one-pot synthesis strategy of PR02. The one-pot synthesis of PR with a low host coverage included the formation of PPR and end-capping reaction in the same system (Scheme 2). In order to optimize the conditions for the enzymatic end-capping reaction with mTGase, the synthesis studies of the PR were carried under different mTGase concentration, reaction time and temperature (Table S1), and the final protocol was fixed as shown in experimental section. The structure of the PR can be confirmed by 1H-NMR and GPC. The 1H-NMR spectrum showed clear signals of H1 protons on cyclodextrin (4.8 ppm, Figure S5) and methylene groups on PEG (3.5 ppm), which can be used to calculate the coverage of the PR. In the GPC results, the molecular weight of PR was larger than PEG axis without a CD peak (Figure S6), which means the CDs showed in 1H-NMR spectra were all capped in the polyrotaxane. This protocol can work well for PEG with different molecular weight (10k-30k) in very high yield (>90%, calculated based on the PEG weight), with 2~3% CD coverage. The PEG30k-based PR was used for further investigation, which was named “PR02” (the PR02-2 in Table S1). The PR02 can be easily dissolved in H2O, DMF and DMSO. This protocol, for the first time, gave the PR with such low coverage and high yield. Additionally, the synthesis avoided the use of toxic reagents, allows the resulting PR to be used easily not only in traditional structural materials but also in biomaterials applications.

ACS Paragon Plus Environment

Chemistry of Materials 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 1. 1 (a) Highly stretchable 16%PR02-3%DVS-hydrogel with a knot; (b) stress-extension ratio curves of PR02 hydrogels with 16%, 20% and 25% PR concentration; (c) loading-unloading tests of PR02 hydrogels with 16%, 20% and 25% PR concentration; (d) successive loading-unloading cycles of the 25%PR02-3%DVS-hydrogel with different strain without stop, and the residual strain after each cycle; (e) successive cyclic tensile tests of the 25%PR02-3%DVS-hydrogel with λ 7 for 100 cycles; (f). relaxation test of the 25%PR02-3%DVS-hydrogel with extension ratio λ 2, 4, and 7, and the loading profile of the stress-relaxation test.

Highly stretchable and instantly recoverable PR02 hydrogel. The PR02 hydrogels were prepared with different polymer and crosslinker (DVS) concentrations. The PR02 hydrogels were transparent, flexible, and exhibited excellent mechanical properties, which were listed in Table S2. The gels can be easily knotted and quickly stretched to more than 10 times in length with a knot (Figure 1a, Movie 1). When the DVS concentration was fixed at 3 wt%, the PR02 hydrogels could be easily extended more than 12 times in length (Figure 1b) with different PR concentration. The 25%PR02-3%DVS-hydrogel exhibited better mechanical performance with ~1.1 MPa stress, ~1600% strain, ~157 J/m2 fracture energy, and afforded ~6.3 MJ/m3 input energy (work of extension W, estimated by calculating the area under the tensile curve) at break, which is comparable to those of other tough hydrogels with energy dissipation.33 When the PR concentration was fixed (16 wt%), the Young’s modulus increased (20- 50 kPa) with increasing crosslinker concentration (Figure S7). Most traditional elastic hydrogels can only afford several tens to a hundred or so kPa stress with 2-8 extension ratio.17, 34-35 Some dissipating-energy hydrogels can dissipate >50% input energy to be extended to more than 10 times length and withstand 0.1-5 MPa stress, but compromise instant recoverability and fatigue resistance.12, 36 PR02 hydrogels, for the first time, emerged as a special recoverable chemical gel with high strength and extensibility. Figure 1c shows the loading-unloading curves of PR02 hydrogels with different PR concentration and 3%DVS, all three gels can completely recover to the original length instantly at room temperature after extending to 10-12 times long with 0.1-0.9 MPa stress. It is noted that the

PR02 hydrogels did not display distinct hysteresis loops. The hysteresis energy of the 16%PR02-3%DVS-hydrogel in loading-unloading cycle with λ =11 was only ~14kJ/m3, about 3% of the input energy; and in loading-unloading cycle with λ =13, the hysteresis energy of the 20%PR023%DVS-hydrogel (~160kJ/m3) and 25%PR02-3%DVShydrogel (~314kJ/m3) were about 7% and 10% of the input energy, respectively. It is suggested that the structure of a PR02 network can almost keep intact under large deformation with the help of the pulley effect. In successive loading-unloading cyclic tests with different extension ratio, the 25%PR02-3%DVS-hydrogel exhibited almost no hysteresis with less than 1% residual strain in the first 3 cycles with λ =2, 4, and 7, and only ~3% residual strain in the fourth cycle with λ =13 (Figure 1d). To investigate the fatigue performance of the PR02 hydrogel, we loaded the 25%PR02-3%DVS-hydrogel for 100 cycles in λ =7 without stop. The stress-extension ratio curves are almost overlapped (Figure 1e), the residual strain after 100 cycles was less than 7%, and the maximum stress reached steady after 5th cycle with only ~5% soften (Figure S8), which is similar to elastic chemical single-network gels. 37 The stress relaxation of 25%PR02-3%DVS-hydrogel was also measured (Figure 1f) in λ =2, 4, and 7, the PR02 hydrogel exhibited almost no relaxation in small deformation (λ =2 and 4), and only relaxed no more than 5% stress at λ =7. Therefore, the CD cross-links can slide on the axis with low friction, and the PR02 hydrogel can exhibit highly elastic and keep the network intact under consecutive, highly-deformed loading-unloading processes, to provide stable and repeatable mechanical properties.

ACS Paragon Plus Environment

Page 4 of 9

Page 5 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials

Figure 2. The influence of the pulley effect on the mechanical properties of polymer hydrogels. (a) Stress-extension ratio curves of PVA, PR02 and PR25 hydrogels with a ~35 kPa Young’s modulus; (b) the relationship between fracture energy (Γ) and Young’s modulus (E) in PVA, PR25 and PR02 hydrogels; (c) crack tip molecular behavior of PVA, PR25 and PR02 hydrogels.

As a kind of chemical single-network hydrogel without energy dissipation, PR02 hydrogel provides the most competitive mechanical properties in terms of strength and extensibility, most likely due to the wide slidable range of the cross-links on axis. Based on its stable and repeatable mechanical properties in high deformation, the PR02 hydrogel has unique and great potential for applications requiring both high strength and fatigue resistance, such as fabricating cartilage, artificial skin, and force sensors. The mechanism discussion. A fundamental understanding of toughening mechanisms of slide-ring hydrogels is critically important for designing the next generation high strength hydrogels with desirable properties. To further investigate the pulley effect in slide-ring gels, the hydrogels based on polyrotaxane with 25% CD coverage (PR25, Mw=35000, Figure S1) and poly(vinyl alcohol) (PVA, Mw=31000) were prepared with 16 wt% polymer concentrations and different crosslinker concentrations as references (Table S3). For hydrogels with the same Young’s modulus (~35kPa, Figure 2a), the maximum elongation and stress of the PR02-hydrogel (~1250% strain, ~125 kPa stress) was substantially greater than that of the PR25-hydrogel (~110% strain, ~50 kPa) or PVA-hydrogel (~180% strain, ~46 kPa stress). For conventional fixed cross-links chemical gels, there is a trade-off relation between fracture energy  and Young’s modulus E: with increasing cross-linking density, the Young’s modulus E increases, while fracture energy  decreases. However, SR gels show an unusual fracture behav-

ior without this trade-off relation.38 In Figure 2b, the fracture energy  plotted against the Young’s modulus for PVA, PR25, and PR02 hydrogels in double logarithm scale. For fixed cross-link 16%PVA hydrogels,  was proportional to the inverse root square of the Young’s modulus with a 0.46 power, which means that increasing cross-linking density decreases fracture toughness. On the other hand,  of the PR25 and PR02 hydrogels was uncorrelated to their initial Young’s modulus as the cross-links can slide along the chain38. The 16%PR02-hydrogels showed constant  values around 55 J/m2, which was much larger than those of 16%PR25-hydrogels (6 J/m2) with a high CD coverage and the same polymer axis length. The slidable range can be estimated from the fracture energy . From the obtained fracture energies, the final monomer number N of one strand between the cross-links before fracture can be calculated based on Eq. S239 and Eq. S4.38 For the same initial Young’s modulus E≈40 kPa, NPVA was calculated to be 128, corresponding to ~18% of the whole axis; NPR25 was around 108, ~15% of the whole axis; while NPR02 was around 477, ~65% of the whole axis. This means that compared to PVA and PR25, PR02 can provide much larger slide range for cross-links (Figure 2c). In PR02 network, ~2/3 length of the polymer strands can be fully utilized to equalize the tension regardless of the initial structure or Young's modulus, and thus improve the strength and toughness of the chemical single-network effectively, to construct a highly stretchable and instantly recoverable hydrogel as we expected.

ACS Paragon Plus Environment

Chemistry of Materials 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 3. 3 (a) Images of the PR02 DMSO gel showing that it could not be easily cut by a knife, and its compressed state; (b) stressstrain curve of the PR02 and PR25 DMSO gel with a ~30 kPa Young’s modulus; (c) elongation state and the corresponding structure of the PR02 DMSO gel; (d) loading-unloading cyclic tensile tests of PR02 DMSO gel with different strain; (e) WAXS results of the fresh PR02 DMSO gel and the crystallized PR02 DMSO gels under different temperature; (f). shape-memory behavior of the PR02 DMSO gel.

PR02 DMSO gel with shape memory behavior. To investigate the performance of the organic gel based on PR with a low CD coverage, PR DMSO gels were prepared by using N, N'-carbonyldiimidazole (CDI) as cross-linker with 16% PR concentration (16%PR02/25-DMSO gel). The resulting PR02-DMSO gels were flexible and not easily broken with a knife (Figure 3a). With the same Young’s modulus (~30 kPa), the 16%PR02-DMSO gel can be stretched to more than 13 times its length with ~160 kPa stress at break, while the PR25-DMSO gel can only be stretched to no larger than twice its length with ~30 kPa stress at break (Figure 3b). The fracture energy (Table S4) of the PR02-DMSO gel (~146 J/m2) is about 20 times larger than that of the PR25-DMSO gel (~7 J/m2). Different from the PR02-hydrogels, the PR02-DMSO gels can only recover shape without hysteresis under small deformation (Figure 3d, 100% strain), but turn to opaque (Figure 3c) and cannot fully recover at room temperature after large deformation (Figure 3d, 500% and 1000% strain). However, the opaque gel can revert to the initial shape and transparent again after heating above 50℃. The structure of the PR02-DMSO gels was analyzed by wideangle X-ray scattering (Figure 3e). The original transparent PR02-DMSO gel exhibited a homogeneous amorphous structure without crystallization peak, while the opaque gel showed clear peaks of PEG crystallization40-41. The PEG crystallization peaks decreased as the opaque sample turned transparent again with the stepwise heating. This reversible orientation-induced crystallization behavior of the PEG, which had never been observed in other PR materials before, is attributed to the very low CD coverage in this work. Unlike conventional high coverage PR, the PR02 only contains a small number of CDs as cross-linkers, which can slide over large distance on the axis under

stretching to relax the internal stress. The PEG chains in PR02-DMSO gels are more exposed outside of the CDs than those in PR25-DMSO ones, and tend to orient and crystallize, resulting in opaque gels (Figure 3c). Based on the synergy of the slide-ring effect and the PEG crystallization, the PR02 DMSO gel can be applied to shape memory materials with excellent mechanical properties (Figure 3f, Movie 2). The shape of the PR02-DMSO gel can be fixed under large deformation, and recover after heating. Conclusion In this work, we proposed a new design strategy to create highly stretchable gels with instant recoverability. A novel commercially scalable synthetic protocol was established in this work for efficiently preparing PR with a low host coverage. By introducing functionalized cyclodextrin and enzymatic end-capping reaction, PR with a CD coverage as low as ~2% was successfully obtained in a high yield of up to 90% without the use of toxic catalysts or organic solvents. The CD cross-links can slip freely along ~2/3 of the axis in PR02, and thus the failure of the corresponding slide-ring network can be avoided even under large deformation. As an elastic hydrogel without energy dissipation, the PR02 hydrogel provided the most competitive mechanical properties with high toughness and instant recoverability, offering great potential to be utilized in applications that require both high mechanical strength and high fatigue resistance, such as cartilage, artificial skin, and force sensors. PR02 DMSO gels exhibited shape memory behavior with large deformation. As the slidable cross-links can be introduce into various structural materials, this work not only push the performance envelope of soft matters, but also opens new opportunities for designing tough materials.

ACS Paragon Plus Environment

Page 6 of 9

Page 7 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials

ASSOCIATED CONTENT Supporting Information. cross-link slidable range calculation method, 1H-NMR spectra and GPC curve of polyrotaxanes, mechanical property data of gels(PDF). The tensile of knotted PR02 hydrogel (movie 1), and the shape memory behavior of PR02 DMSO gel (movie 2).

AUTHOR INFORMATION Corresponding Author *L. Jiang Email: [email protected] *K. Ito Email: [email protected]

Author Contributions The manuscript was written through contributions of all authors.

Funding Sources This work was supported by AIST-UTokyo Advanced Operando-Measurement Technology Open Innovation Laboratory (OPERANDO-OIL) and ImPACT Program of Council for Science, Technology and Innovation (Cabinet Office, Government of Japan).

ACKNOWLEDGMENT The wide-angle and small-angle X-ray scattering experiments were performed at BL05SS at Spring-8, Hyogo, Japan. The mTGase is provided by Ajinomoto. Co. (Tokyo, Japan).

ABBREVIATIONS 1H-NMR,

Proton Nuclear magnetic resonance; GPC, Gel permeation chromatography; DMF, Dimethylformamide; DMSO, Dimethyl sulfoxide.

REFERENCES (1) Lee, K. Y.; Mooney, D. J. Hydrogels for tissue engineering. Chem. Rev. 2001, 101, 1869-1879. (2) Qiu, Y.; Park, K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Del. Rev. 2001, 53, 321-339. (3) Dong, L.; Agarwal, A. K.; Beebe, D. J.; Jiang, H. R. Adaptive liquid microlenses activated by stimuli-responsive hydrogels. Nature 2006, 442, 551-554. (4) Sakai, T.; Matsunaga, T.; Yamamoto, Y.; Ito, C.; Yoshida, R.; Suzuki, S.; Sasaki, N.; Shibayama, M.; Chung, U. I. Design and fabrication of a high-strength hydrogel with ideally homogeneous network structure from tetrahedron-like macromonomers. Macromolecules 2008, 41, 5379-5384. (5) Gong, J. P.; Katsuyama, Y.; Kurokawa, T.; Osada, Y. Doublenetwork hydrogels with extremely high mechanical strength. Adv. Mater. 2003, 15, 1155-1158. (6) Gong, J. P. Materials both Tough and Soft. Science 2014, 344, 161-162. (7) Lin, P.; Ma, S. H.; Wang, X. L.; Zhou, F. Molecularly Engineered Dual-Crosslinked Hydrogel with Ultrahigh Mechanical Strength, Toughness, and Good Self-Recovery. Adv. Mater. 2015, 27, 2054-2059. (8) Zhong, M.; Liu, Y. T.; Liu, X. Y.; Shi, F. K.; Zhang, L. Q.; Zhu, M. F.; Xie, X. M. Dually cross-linked single network poly(acrylic acid) hydrogels with superior mechanical properties and water absorbency. Soft Matter 2016, 12, 5420-5428. (9) Sun, G. X.; Li, Z. J.; Liang, R.; Weng, L. T.; Zhang, L. N. Super stretchable hydrogel achieved by non-aggregated spherulites with diameters < 5nm. Nat. Commun. 2016, 7, 12095-12102.

(10) Haraguchi, K.; Takehisa, T. Nanocomposite hydrogels: A unique organic-inorganic network structure with extraordinary mechanical, optical, and swelling/de-swelling properties. Adv. Mater. 2002, 14, 1120-1124. (11) Sun, J. Y.; Zhao, X. H.; Illeperuma, W. R. K.; Chaudhuri, O.; Oh, K. H.; Mooney, D. J.; Vlassak, J. J.; Suo, Z. G. Highly stretchable and tough hydrogels. Nature 2012, 489, 133-136. (12) Sun, T. L.; Kurokawa, T.; Kuroda, S.; Bin Ihsan, A.; Akasaki, T.; Sato, K.; Haque, M. A.; Nakajima, T.; Gong, J. P. Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity. Nat. Mater. 2013, 12, 932-937. (13) Xia, S.; Song, S. X.; Ren, X. Y.; Gao, G. H. Highly tough, antifatigue and rapidly self-recoverable hydrogels reinforced with core-shell inorganic-organic hybrid latex particles. Soft Matter 2017, 13, 6059-6067. (14) Hou, J. L.; Ren, X. Y.; Guan, S.; Duan, L. J.; Gao, G. H.; Kuai, Y.; Zhang, H. X. Rapidly recoverable, anti-fatigue, super-tough double-network hydrogels reinforced by macromolecular microspheres. Soft Matter 2017, 13, 1357-1363. (15) Okumura, Y.; Ito, K. The polyrotaxane gel: A topological gel by figure-of-eight cross-links. Adv. Mater. 2001, 13, 485-487. (16) Ito, K. Slide-ring materials using topological supramolecular architecture. Current Opinion in Solid State & Materials Science 2010, 14, 28-34. (17) Bin Imran, A.; Esaki, K.; Gotoh, H.; Seki, T.; Ito, K.; Sakai, Y.; Takeoka, Y. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network. Nat. Commun. 2014, 5, 5124. (18) Minato, K.; Mayumi, K.; Maeda, R.; Kato, K.; Yokoyama, H.; Ito, K. Mechanical properties of supramolecular elastomers prepared from polymer-grafted polyrotaxane. Polymer 2017, 128, 386-391. (19) Jiang, L.; Kato, K.; Mayumi, K.; Yokoyama, H.; Ito, K. OnePot Synthesis and Characterization of Polyrotaxane-Silica Hybrid Aerogel. Acs Macro Lett 2017, 6, 281-286. (20) Choi, S.; Kwon, T. W.; Coskun, A.; Choi, J. W. Highly elastic binders integrating polyrotaxanes for silicon microparticle anodes in lithium ion batteries. Science 2017, 357, 279-283. (21) Kato, K.; Okabe, Y.; Okazumi, Y.; Ito, K. A significant impact of host-guest stoichiometry on the extensibility of polyrotaxane gels. Chem. Commun. 2015, 51, 16180-16183. (22) Araki, J.; Zhao, C. M.; Kohzo, I. Efficient production of polyrotaxanes from alpha-cyclodextrin and poly(ethylene glycol). Macromolecules 2005, 38, 7524-7527. (23) Fujita, H.; Ooya, T.; Yui, N. Thermally induced localization of cyclodextrins in a polyrotaxane consisting of beta-cyclodextrins and poly(ethylene glycol)-poly(propylene glycol) triblock copolymer. Macromolecules 1999, 32, 2534-2541. (24) Ren, L. X.; Ke, F. Y.; Chen, Y. M.; Liang, D. H.; Huang, J. Supramolecular ABA triblock copolymer with polyrotaxane as B block and its hierarchical self-assembly. Macromolecules 2008, 41, 5295-5300. (25) Zhang, X. W.; Zhu, X. Q.; Tong, X. M.; Ye, L.; Zhang, A. Y.; Feng, Z. G. Novel main-chain polyrotaxanes synthesized via ATRP of HPMA in aqueous media. J. Polym. Sci. Pol. Chem. 2008, 46, 5283-5293. (26) Sun, H. Y.; Han, J.; Gao, C. High yield production of high molecular weight poly(ethylene glycol)/alpha-cyclodextrin polyrotaxanes by aqueous one-pot approach. Polymer 2012, 53, 2884-2889. (27) Yu, S. L.; Yuan, J. T.; Shi, J. H.; Ruan, X. J.; Wang, Y. L.; Gao, S. F.; Du, Y. One-pot synthesis of water-soluble, beta-cyclodextrinbased polyrotaxanes in a homogeneous water system and its use in bio-applications. J. Mater. Chem. B 2015, 3, 5277-5283. (28) Seo, J. H.; Yui, N. The effect of molecular mobility of supramolecular polymer surfaces on fibroblast adhesion. Biomaterials 2013, 34, 55-63. (29) Fleury, G.; Brochon, C.; Schlatter, G.; Bonnet, G.; Lapp, A.; Hadziioannou, G. Synthesis and characterization of high molecular

ACS Paragon Plus Environment

Chemistry of Materials 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

weight polyrotaxanes: towards the control over a wide range of threaded alpha-cyclodextrins. Soft Matter 2005, 1, 378-385. (30) Bai, R. B.; Yang, J. W.; Morelle, X. P.; Yang, C. H.; Suo, Z. G. Fatigue Fracture of Self-Recovery Hydrogels. Acs Macro Lett 2018, 7, 312-317. (31) Harada, A. Preparation and structures of supramolecules between cyclodextrins and polymers. Coord. Chem. Rev. 1996, 148, 115-133. (32) Motoki, M.; Seguro, K. Transglutaminase and its use for food processing. Trends Food Sci. Technol. 1998, 9, 204-210. (33) Naficy, S.; Spinks, G. M.; Wallace, G. G. Thin, Tough, pHSensitive Hydrogel Films with Rapid Load Recovery. Acs Appl. Mater. Inter. 2014, 6, 4109-4114. (34) Sakai, T.; Akagi, Y.; Matsunaga, T.; Kurakazu, M.; Chung, U.; Shibayama, M. Highly Elastic and Deformable Hydrogel Formed from Tetra-arm Polymers. Macromol. Rapid Commun. 2010, 31, 1954-1959. (35) Kamata, H.; Akagi, Y.; Kayasuga-Kariya, Y.; Chung, U.; Sakai, T. "Nonswellable" Hydrogel Without Mechanical Hysteresis. Science 2014, 343, 873-875. (36) Jia, H. Y.; Huang, Z. J.; Fei, Z. F.; Dyson, P. J.; Zheng, Z.; Wang, X. L. Unconventional Tough Double-Network Hydrogels with Rapid Mechanical Recovery, Self-Healing, and Self-Gluing Properties. Acs Appl. Mater. Inter. 2016, 8, 31339-31347. (37) Bai, R. B.; Yang, Q. S.; Tang, J. D.; Morelle, X. P.; Vlassak, J.; Suo, Z. G. Fatigue fracture of tough hydrogels. Extreme Mech. Lett. 2017, 15, 91-96. (38) Liu, C.; Kadono, H.; Mayumi, K.; Kato, K.; Yokoyama, H.; Ito, K. Unusual Fracture Behavior of Slide-Ring Gels with Movable Cross-Links. Acs Macro. Lett. 2017, 6 (12), 1409-1413. (39) Thomas, G. J. L. a. A. G., The Strength of Highly Elastic Materials. Proceedings of the Royal Society A 1967, 300, 108-119. (40) Nomoto, Y.; Matsunaga, T.; Sakai, T.; Tosaka, M.; Shibayama, M., Structure and physical properties of dried TetraPEG gel. Polymer 2011, 52, 4123-4128. (41) Tien, N. D.; Hoa, T. P.; Mochizuki, M.; Saijo, K.; Hasegawa, H.; Sasaki, S.; Sakurai, S., Higher-order crystalline structures of poly(oxyethylene) in poly(D,L-lactide)/poly(oxyethylene) blends. Polymer 2013, 54, 4653-4659.

ACS Paragon Plus Environment

Page 8 of 9

Page 9 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Chemistry of Materials

Table of Contents

ACS Paragon Plus Environment

9