Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network — TEI-tagged view

Abu Bin ImranpersName, Kenta EsakipersName, Hiroaki GotohpersName, Takahiro SekipersName, Kohzo ItopersName, Yasuhiro SakaipersName, Yukikazu TakeokapersName (2014date). “Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network.” Nature Communicationstitle·j.

Object of study — thermosensitiveterm·key poly(NIPAterm) hydrogelsterm·key cross-linked by polyrotaxaneterm·dom derivatives with ionic groups

Research question — how to make stimuli-sensitiveterm·key hydrogelsterm·key that are not brittle

Contribution — polyrotaxaneterm·dom cross-linkersterm·key that improve the mechanical properties of a wide variety of polymer gels

Full text — tagged

Extremely stretchable thermosensitiveterm·key hydrogelsterm·key by introducing slide-ring polyrotaxaneterm·dom cross-linkersterm·key and ionic groups into the polymer network Abstract Stimuli-sensitiveterm·key hydrogelsterm·key changing their volumes and shapes in response to various stimulations have potential applications in multiple fields. However, these hydrogelsterm·key have not yet been commercialized due to some problems that need to be overcome. One of the most significant problems is that conventional stimuli-sensitiveterm·key hydrogelsterm·key are usually brittle. Here we prepare extremely stretchable thermosensitiveterm·key hydrogelsterm·key with good toughness by using polyrotaxaneterm·dom derivatives composed of α-cyclodextrinterm and polyethylene glycolterm as cross-linkersterm·key and introducing ionic groups into the polymer network. The ionic groups help the polyrotaxaneterm·dom cross-linkersterm·key to become well extended in the polymer network. The resulting hydrogelsterm·key are surprisingly stretchable and tough because the cross-linked α-cyclodextrinterm molecules can move along the polyethylene glycolterm chains. In addition, the polyrotaxaneterm·dom cross-linkersterm·key can be used with a variety of vinyl monomers; the mechanical properties of the wide variety of polymer gels can be improved by using these cross-linkersterm·key.

Numerous fundamental studies have investigated the chemistry and physics of polymer gels 1 . The properties of polymer gels, such as their molecular sieving ability, solvent retention and ability to serve as a corrective artificial lens, are already widely exploited in the pharmaceutical, medical and engineering fields. These polymer gels have broad utility in various fields, because the preparation of general polymer gels is exceedingly simple. For example, a poly(acrylamide) gel, which is used in electrophoresis in molecular biology, is usually prepared as follows: first, a predetermined quantity of monomer (acrylamide), cross-linkerterm·key ( N , N ′-methylenebisacrylamide (BISterm)) and initiator (for example, ammonium persulphate (APS)) are dissolved in pure water or a buffer solution. Next, the solution is deaerated under reduced pressure. Finally, the polymer gel is prepared by adding a few drops of accelerator ( N , N , N ′, N ′-tetramethylethylenediamine (TEMED)) into the solution.

Currently, the study of stimuli-sensitive polymer gelsterm·dom, which undergo volume and shape changes in response to a stimulus, is becoming a highly active field of polymer gel research 2 , 3 . Stimuli-sensitive polymer gelsterm·dom that exhibit reversible changes in their selective permeability to molecules, surface wettability and ability to convert chemical energy into mechanical energy have been reported to be promising for drug delivery systems 4 , artificial muscles 5 , 6 and sensors 7 , 8 , 9 , 10 . Although stimuli-sensitive polymer gelsterm·dom were first studied more than a few decades ago, they have not yet been commercialized for applications. One of the most significant problems is that conventional stimuli-sensitive polymer gelsterm·dom are usually mechanically weak or brittle. For example, chemically cross-linked stimuli-sensitive polymer gelsterm·dom are broken by only 1.2–1.5 times under uniaxial stretching 11 . In general, chemically cross-linked polymer gels (hereafter referred to as ‘chemical polymer gelsterm·dom’) exhibit rubber-like elasticity but are brittle and easily broken under deformation. The weak mechanical properties of chemical polymer gelsterm·dom are due to the inhomogeneous network structureterm·dom generated during the polymerization, which are demonstrated by, for example, spatially non-uniform cross-linking densities and randomly distributed chain lengths between the cross-links 12 . When the shape of a bulk chemical polymer gelterm·dom is distorted by an external force, the stress on the polymer network is concentrated on shorter polymer chains. As a result, the polymer network is mechanically disrupted. Similarly, when an abrupt environmental change leads to a modification in the volume or shape of a stimuli-sensitiveterm·key chemical polymer gelterm·dom, the polymer network fractures for the same reason 13 . Therefore, the weak mechanical properties of conventional stimuli-sensitive polymer gelsterm·dom make them unsuitable for practical applications.

Numerous attempts to improve the mechanical properties of polymer gels have been reported thus far 14 , 15 , 16 , 17 ; most of the improved polymer gels have specially structured polymer networks, such as interpenetrating polymer networks 14 and coupled networks between two types of four-armed polymers 16 , which enable them to exhibit excellent mechanical performance. However, the stimuli sensitivities of these chemical polymer gelsterm·dom have not been adequately investigated. In most cases, to obtain the desired stimuli-sensitiveterm·key behaviour, the chemical components of these polymer gel networks must be altered by introducing stimuli-sensitiveterm·key functional groups or monomers. Hydrogelsterm·key that contain inorganic nanoparticles as cross-linkersterm·key can be easily prepared using stimuli-sensitiveterm·key polymers and can be highly stretchable and tough 18 . However, the types of polymers that can be used to prepare these hydrogelsterm·key are limited, and the hydrogelsterm·key might dissolve in water during long-term utilization because the main cross-linking structures are hydrogen bonds between the inorganic nanoparticles and polymers.

To make stimuli-sensitiveterm·key hydrogelsterm·key for various practical applications, the mechanical properties of the existing well-studied stimuli-sensitiveterm·key hydrogelsterm·key should be improved retaining their stimuli sensitivities and using simple preparation techniques. This advance in stimuli-sensitiveterm·key hydrogelterm·key research requires, for instance, a breakthrough in the cross-linking structure in conventional stimuli-sensitiveterm·key hydrogelsterm·key, although the cross-linking structure constitutes a small fraction of the hydrogelsterm·key. On the basis of this requirement, a slide-ring gelterm·dom developed by Okumura and ItopersName 19 inspired us to prepare a new cross-linkerterm·key for mechanically improved stimuli-sensitiveterm·key hydrogelsterm·key. This slide-ring gelterm·dom is composed of polyrotaxaneterm·dom (PRterm·dom) 20 , which consists of α-cyclodextrinterm (α-CDterm), polyethylene glycolterm (PEGterm) with terminal carboxylic acids and a capping agent (1-adamantanamine). In the slide-ring gelterm·dom, α-CDsterm in one PRterm·dom are cross-linked to α-CDsterm in different PRsterm·dom. The PEGterm main chains are not fixed at the cross-linking points in the polymer network; instead, they can pass through the hole of a figure-8-shaped junction of cross-linked α-CDsterm freely, which is called the ‘pulley effectterm·dom’. The concentration of stress on part of the polymer network is minimized through this effect. As a result, the slide-ring gelterm·dom exhibits high extensibility and a small hysteresis on repeated extension and contraction.

Here we prepare thermosensitiveterm·key hydrogelsterm·key using PRterm·dom as a cross-linkerterm·key to exploit the pulley effectterm·dom. N -Isopropylacrylamideterm (NIPAterm) is used as the monomer because it is known to form thermosensitiveterm·key polymers and polymer gels in water 21 , 22 . We also introduce ionic sites into the PR-cross-linked polymer network using two different methods to obtain extremely stretchable and tough thermosensitiveterm·key hydrogelsterm·key. The ionic groups help the PRterm·dom cross-linkersterm·key to become well extended in the polymer network. The resulting hydrogelsterm·key are stretchable and tough, similar to soft rubbers, because the cross-linked α-CDterm molecules can move along the PEGterm chains.

Results Past approach of hydrogelsterm·key by PRsterm·dom as cross-linkersterm·key Several previous attempts have been made to prepare stretchable hydrogelsterm·key using PRsterm·dom as the cross-linkerterm·key. We first prepared a NIPA-based hydrogelterm·key using a PRterm·dom modified by 2-acryloyloxyethyl isocyanate, which contains both isocyanate and vinyl groups, as the cross-linkerterm·key (PR-C) 23 . The isocyanate groups form stable carbamate bonds with the α-CDterm hydroxyl groups in the PRterm·dom to generate the cross-linking structures. It was expected that the NIPAterm–PR-C hydrogelterm·key would exhibit high extensibility, similar to the slide-ring gelterm·dom composed of only the PRterm·dom; however, the mechanical properties of the hydrogelterm·key were only slightly improved compared with those of chemical poly(NIPAterm) hydrogelsterm·key prepared using conventional cross-linkersterm·key such as BISterm. Although the NIPAterm–PR-C gel prepared in dimethyl sulphoxide (DMSO) was transparent, the gel became slightly opaque after replacing DMSO with water, even at 20 °C. These characteristics were attributed to the possibility that PR-C was in a contracted state in the hydrogelterm·key. The unmodified PRterm·dom, which consists of α-CDsterm and PEGterm, is soluble only in a few solvents, such as DMSO, some ionic liquids, mixtures of organic amides and lithium salts and high-pH aqueous solutions. It is insoluble in pure water because the α-CDterm molecules aggregate due to hydrogen bonding between the hydroxyl groups on α-CDsterm 24 . Thus, α-CDsterm could not move along the PEGterm chains, and the pulley effectterm·dom was restricted in water. As a result, the PRterm·dom slide-ring gelterm·dom appeared opaque and did not exhibit high extensibility. In high-pH aqueous solutions, such as a sodium hydroxide (NaOH) aqueous solution, the α-CDsterm do not aggregate through hydrogen bonding due to the ionization of the α-CDterm hydroxyl groups by NaOH; as a result, the slide-ring gelterm·dom could swell 19 . However, a stimuli-sensitiveterm·key hydrogelterm·key that is only useful in high-pH aqueous solutions does not have broad utility. Even when a nonionic, water-soluble hydroxypropylated PRterm·dom cross-linkerterm·key (HPR-Cterm; Fig. 1a ) was used, the resulting NIPA-based hydrogelterm·key did not exhibit greater extensibility than chemical poly(NIPAterm) hydrogelsterm·key 25 . Although this hydrogelterm·key was nearly transparent, the pulley effectterm·dom might not have worked well in this hydrogelterm·key because the solubility of HPR-Cterm in water might be insufficient.

Preparation of the polyelectrolyte hydrogelsterm·key using nonionic PRterm·dom cross-linkerterm·key. ( a ) Preparation of HPR-Cterm from HPR, 2-acryloyloxyethyl isocyanate, DBTDL (catalyst) and BHT (polymerization inhibitor) in DMSO. ( b ) Preparation of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key from HPR-Cterm (cross-linkerterm·key), NIPAterm (main monomer), AAcNaterm (comonomer), APS (initiator) and TEMED (accelerator) in water.

Polyelectrolyte hydrogelsterm·key by nonionic PRterm·dom cross-linkerterm·key If polyelectrolyte hydrogelsterm·key are prepared using NIPAterm, the ionic monomer sodium acrylic acidterm (AAcNaterm), and HPR-Cterm ( Fig. 1b ), the obtained hydrogelsterm·key (NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key) are highly stretchable, flexible and durable when compressed ( Fig. 2 ). Thus, the mechanical properties of these hydrogelsterm·key are completely different from those of all existing chemical poly(NIPAterm) hydrogelsterm·key and chemical poly(NIPAterm–AAcNaterm) hydrogelsterm·key ( Supplementary Movies 1 and 2 ). These hydrogelsterm·key are so strong that they cannot be easily cut with a knife ( Fig. 2d ). Interestingly, the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key rapidly shrink isotropically without undergoing any deformation at the gel surface ( Supplementary Fig. 4 ). Furthermore, these hydrogelsterm·key can absorb up to several tens of thousands percentage weight of water compared with their dried state. For example, the weight of a hydrogelterm·key with 0.65 wt% of HPR-Cterm increases by up to 620-fold when it is placed in water ( Fig. 2e ). Figure 2f shows the stress–strain curves of NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key with different amounts of HPR-Cterm and chemical poly(NIPAterm–AAcNaterm) hydrogelsterm·key with different amounts of BISterm. Young’s moduli, maximum elongationterm·dom ratios and tensile strengths are summarized in Supplementary Table 2 . For hydrogelsterm·key with similar cross-linkerterm·key concentrations (0.63–0.65 wt%), the maximum elongationterm·dom of the hydrogelsterm·key with the HPR-Cterm cross-linkerterm·key (912%) is substantially greater than that of the hydrogelsterm·key with the BISterm cross-linkerterm·key (29%); the extensibility and toughness of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key are improved greatly by replacing the BISterm cross-linkerterm·key with HPR-Cterm. In addition, NIPAterm–AAcNaterm–BISterm (0.063 wt%) and NIPAterm–AAcNaterm–HPR-Cterm (0.65 wt%) hydrogelsterm·key have similar cross-linking density due to the presence of equal number of active vinyl groups in the cross-linkersterm·key BISterm and HPR-Cterm used for gelation ( Supplementary Table 1 ). However, NIPAterm–AAcNaterm–BISterm (0.063 wt%) hydrogelterm·key exhibits high stiffness and very poor tensile strength compared with NIPAterm–AAcNaterm–HPR-Cterm (0.65 wt%) hydrogelterm·key. When the amount of HPR-Cterm increases to 1.21 and 2.00 wt%, Young’s modulus and tensile strength are enhanced. In the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key, the AAcNaterm component is ionized. The Na + counter ions cannot stay near the ionized poly(NIPAterm–AAc − ) polymer chains and thus move long distances away from them, making them stretch, to achieve a large gain in entropy 22 . The aggregation of the α-CDterm molecules at the HPR-Cterm cross-linkerterm·key can be prevented by stretching the poly(NIPAterm–AAc − ) chains ( Fig. 2g ). As a result, the α-CDterm molecules can move along the PRterm·dom main chains, and the pulley effectterm·dom might occur.

Properties of the polyelectrolyte hydrogelsterm·key using nonionic PRterm·dom cross-linkerterm·key. ( a ) Elongated state of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key. ( b ) Compressed state of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key. ( c ) Coiled and knotted states of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key. ( d ) The NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key could not be easily cut with a knife. ( e ) Swelling of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key in water. Left: the dry gel (129 mg); right: the water-swollen gel (80 g). The NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm absorbs up to ca. 62,000 wt% of water in its dry state. ( f ) Stress–strain curves of hydrogelsterm·key: (i) NIPAterm–AAcNaterm–BISterm (0.65 wt%), (ii) NIPAterm–AAcNaterm–BISterm (0.065 wt%), (iii) NIPAterm–AAcNaterm–HPR-Cterm (2.00 wt%), (iv) NIPAterm–AAcNaterm–HPR-Cterm (1.21 wt%) and (v) NIPAterm–AAcNaterm–HPR-Cterm (0.65 wt%). ( g ) Schematic of swollen HPR-Cterm in the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key.

These excellent mechanical properties of this hydrogelterm·key are most likely achieved because of the homogeneous network structure afforded by the pulley effectterm·dom. To confirm the structural homogeneity of the hydrogelsterm·key, their structures were analysed under uniaxial elongation by small-angle X-ray scatteringterm·mth (SAXSterm·mth). In general, the spatial inhomogeneity of cross-links is hidden by the fluctuation in the polymer chain concentration before the elongation. When the chemical gels are deformed, the inhomogeneous structure is exposed and the two-dimensional (2D) X-ray or neutron scattering patterns become elliptical 26 . Figure 3a shows 2D SAXSterm·mth patterns of as-prepared (elongation ratio ε =1) and vertically stretched ( ε >1) NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key cross-linked with 0.65 wt% HPR-Cterm. These patterns are almost isotropic, which is consistent with the results for slide-ring gelsterm·dom in a good solvent 27 . This hydrogelterm·key contains water, which is a good solvent; therefore, it has no internal aggregation structure. The SAXSterm·mth pattern of this hydrogelterm·key remains isotropic when the hydrogelterm·key is elongated by a factor of greater than four, which is in contrast to the elliptical pattern observed for a poly(acrylamide) gel when elongated by a factor of 1.5 (ref. 27) 27 . We quantitatively evaluated the SAXSterm·mth patterns by calculating the sector average of the intensity in the directions of parallel and perpendicular to the elongation. The angle of the sector was 20° in each direction. Figure 3b shows the sector-averaged scattering profiles of the hydrogelterm·key at elongation ratios of ε =1–4 in each direction. The scattering function for polymer gels in a good solvent is given as follows 28 , 29 : SAXSterm·mth results of the polyelectrolyte hydrogelsterm·key using nonionic PRterm·dom cross-linkerterm·key. ( a ) SAXSterm·mth isointensity patterns of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm for different elongations in the vertical direction. ( b ) Sector-averaged I ( q ) of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm for different elongations in the parallel (open circles) and perpendicular (filled circles) directions. The solid lines are the equation (1) fitting results. ( c ) Stretching ratio dependence of ξ and Ξ for the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm in parallel to the elongation direction, and ( d ) stretching ratio dependence of ξ and Ξ for the NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm in perpendicular to the elongation direction.

The first term on the right side of equation (1) is a Lorentzian functionterm·mth (that is, an Ornstein–Zernike functionterm·mth) that describes the polymer concentration fluctuation, and the second term is a squared Lorentzian functionterm·mth (that is, a Debye–Bueche functionterm·mth) that describes excess scattering from a spatial inhomogeneity. The parameter q is the magnitude of the scattering vector, ξ is the correlation length of the fluctuation and Ξ is the characteristic length of the inhomogeneity. The I 1 and I 2 terms are the scattering intensities at q =0 that correspond to the static and dynamic contributions, respectively. An analysis of the sector-averaged intensity profile using equation (1) gives ξ and Ξ as fitting parameters. According to the results of previous SAXSterm·mth studies on conventional chemical gels, Ξ in the elongation direction increases as the elongation ratio increases, which indicates that conventional chemical gels have spatial inhomogeneities in their cross-linking structures that are magnified on elongation 30 . The fitting results are shown in the scattering profiles in Fig. 3b . Figure 3c,d shows the elongation ratio dependence of ξ and Ξ in each direction. The ξ parameter is nearly constant at ~10–20 Å for all the elongation ratios studied. For elongated gels, the Ξ parameter does not change significantly or slightly decreases as the elongation ratio increases, which indicates that the inhomogeneity of this hydrogelterm·key is much lower than that of the conventional chemical hydrogelsterm·key. This behaviour is the same as that observed in small-angle neutron scattering studies of slide-ring gelsterm·dom 31 and is significantly different from that of chemical gels 30 . Thus, the SAXSterm·mth results in this study demonstrate the spatial homogeneity of the polymer network and the pulley effectterm·dom in the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key.

Hydrogelsterm·key using ionic PRterm·dom cross-linkerterm·key Furthermore, to obtain a wide variety of thermosensitiveterm·key hydrogelsterm·key with mechanical toughness and superb functionality, the thermo-responsiveness must be efficiently regulated while maintaining the enhanced mechanical properties. Thus, we demonstrate a case in which the thermo- and pH-responses of PR-cross-linked hydrogelsterm·key are regulated by controlling the spatial distribution of the ion concentration in the hydrogelsterm·key.

The pure poly(NIPAterm) hydrogelterm·key without any ionic species undergoes a volume change at 32 °C (ref. 21 ). For hydrogelsterm·key consisting of randomly copolymerized NIPAterm and ionic monomers, the characteristic temperature of the volume change generally increases with increasing ionic monomer concentration. However, the volume of the hydrogelterm·key does not change when a large amount of ionic monomers are present in the hydrogelterm·key 22 ; the strongly hydrated ions distributed throughout the whole polymer network inhibit the dehydration of the polymer chains. Interestingly, the temperature-sensitive swelling behaviours of random and graft copolymer hydrogelsterm·key composed of NIPAterm and ionic monomers are dramatically different. The volume-change temperatures of the graft copolymer hydrogelsterm·key have been reported to be similar to that of the pure poly(NIPAterm) hydrogelterm·key because the coil-globule transition of the poly(NIPAterm) portion is not affected by the grafted polymer composed of ionic monomers 32 , 33 .

On the basis of the graft copolymer hydrogelterm·key properties, we successfully prepared pure poly(NIPAterm) hydrogelsterm·key without ions that exhibit both mechanical toughness and thermo-responsiveness utilizing an ionic PRterm·dom derivative as a cross-linkerterm·key ( Fig. 4a ). This PRterm·dom cross-linkerterm·key (iPR-Cterm) has carboxyl groups on the α-CDterm molecules, making it highly water soluble. It was expected that iPR-Cterm can be well extended in a neutral poly(NIPAterm) network ( Fig. 4b ), as observed for HPR-Cterm in the polyelectrolyte network ( Fig. 2g ). The most distinctive feature of the iPR-Cterm gels is that the ionic groups are localized only on the PRterm·dom cross-linkerterm·key. The spatial distribution of the ionic groups on the polymer network is therefore remarkably different from that in the randomly copolymerized NIPAterm–AAcNaterm gels. As expected, the iPR-Cterm hydrogelsterm·key are as transparent, stretchable and tough in pure water ( Fig. 4d ; Supplementary Table 3 ; Supplementary Movie 3 ) as the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key. The degree of dissociation of the carboxylic acid groups in the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key changes with pH, and the osmotic pressure in the hydrogelsterm·key therefore changes with pH because the ionic AAcNaterm monomer is distributed throughout the polymer network. As a result, the swelling behaviour of the NIPAterm–AAcNaterm–HPR-Cterm hydrogelsterm·key is highly dependent on the solvent pH ( Fig. 5a ). However, the swelling behaviour of the NIPAterm–iPR-Cterm hydrogelsterm·key shows little dependence on the solvent pH when the amount of iPR-Cterm is lower than 3 wt% ( Supplementary Figs 5 and 6 ). Although the carboxyl groups of iPR-Cterm can also dissociate in water in response to changes in the pH, the dissociated ion does not affect the transition temperature significantly because the amount of iPR-Cterm is very small and the ionic groups are localized only on the iPR-Cterm cross-linkerterm·key. Thus, the pH dependence of the temperature response is successfully regulated by controlling the spatial distribution of the ionic groups in the hydrogelsterm·key via simple chemical modifications of the PRterm·dom.

Preparation of the hydrogelsterm·key using ionic PRterm·dom cross-linkerterm·key. ( a ) Preparation of iPR-Cterm from iPR, 2-acryloyloxyethyl isocyanate, DBTDL (catalyst) and BHT (polymerization inhibitor) in DMSO. ( b ) Schematic of swollen iPR-Cterm in the NIPAterm–iPR-Cterm hydrogelterm·key. ( c ) Elongated state of the NIPAterm–iPR-Cterm hydrogelterm·key. ( d ) Stress–strain curves for NIPAterm–iPR-Cterm hydrogelsterm·key with different amounts of iPR-Cterm.

Swelling behaviours of the polyelectrolyte hydrogelsterm·key using nonionic PRterm·dom cross-linkerterm·key and the hydrogelsterm·key using ionic PRterm·dom cross-linkerterm·key. The degree of swelling D / D 0 for the ( a ) NIPAterm–AAcNaterm–HPR-Cterm hydrogelterm·key with 0.65 wt% of HPR-Cterm during both heating (red) and cooling (blue) processes, and ( b ) NIPAterm–iPR-Cterm hydrogelterm·key with 0.80 wt% of iPR-Cterm during heating process in aqueous solutions with different pHs as a function of temperature. D and D 0 denote the gel diameters at equilibrium and on synthesis, respectively.

Discussion We demonstrate the simple preparation of extremely stretchable hydrogelsterm·key with temperature and pH sensitivities by using PRterm·dom derivatives as cross-linkersterm·key and introducing ionic sites into the polymer network via two different methods. One method involves randomly copolymerizing NIPAterm and ionic AAcNaterm with HPR-Cterm as the cross-linkerterm·key. Because of the considerable swelling power of the polyelectrolyte hydrogelsterm·key, HPR-Cterm, which might be in a contracted state in the poly(NIPAterm) hydrogelterm·key, achieves a swollen coil state, and the pulley effectterm·dom is observed. The resulting hydrogelsterm·key exhibit significant pH sensitivity because of the electrostatic repulsion between the charges on the polymer chains and the effect of pH on the osmotic pressure of the counter ions. This finding is significant for improving existing polyelectrolyte hydrogelsterm·key. Although current polyelectrolyte hydrogelsterm·key have the potential to absorb and release large amounts of solvents 34 , recognize or react with specific molecules 35 , 36 , 37 and be employed in artificial muscles 5 , 6 , their brittleness must be reduced before they can be used in these applications. The PR-based cross-linkerterm·key developed here can lead to significant improvements in the mechanical properties of existing polyelectrolyte hydrogelsterm·key without compromising their characteristic properties. Alternatively, iPR-Cterm can be widely employed as a cross-linkerterm·key to improve the mechanical properties of a broad range of existing polymer gels, including non-polyelectrolyte gels, because it does not require the use of an ionic monomer to obtain enhanced mechanical properties. Therefore, the mechanical properties of existing well-studied stimuli-sensitiveterm·key hydrogelsterm·key can be improved without compromising their stimuli sensitivities by using iPR-Cterm.

In conclusion, extremely stretchable and tough thermosensitiveterm·key hydrogelsterm·key were obtained by using PRterm·dom cross-linkersterm·key and introducing ionic sites into the polymer network. Two different preparation methods were employed. Our results indicate that using a small amount of a supramolecular building block as a cross-linkerterm·key in a polymer network results in dramatic changes in its mechanical properties. Using the preparation methods described here, which are simple, like conventional polymer gel preparation techniques, the mechanical properties of various polymer gels can be improved. Thus, stimuli-sensitiveterm·key hydrogelsterm·key with good mechanical performance and controllable functionality can be produced for drug delivery systems, tissue engineering, artificial muscles and sensors. Substantial progress is being made towards the practical use of stimuli-sensitiveterm·key hydrogelsterm·key for these applications.

Methods Materials HPR ( M n =126,000; M w / M n =1.4; inclusion ratio of α-CDterm: 29%) and ionic PRterm·dom (iPR: M n =156,000; M w / M n =1.4; inclusion ratio of α-CDterm: 23%) were purchased from Advanced Soft Materials (Kashiwa, Japan) and were used without further purification. NIPAterm was purified by recrystallization from toluene/ n -hexane. AAcNaterm (Sigma-Aldrich, MO, USA), 2,2′-methylenebisacrylamide (BISterm; Acros Organics, Geel, Belgium), APS (Acros Organics), TEMED (Wako Pure Chemical Industries, Tokyo, Japan), dibutyltin dilaurate (DBTDL; Tokyo Kasei Kogyo, Tokyo, Japan) and butyl hydroxyl toluene (BHT; Tokyo Kasei Kogyo) were purchased as reagent-grade materials and used as received. 2-acryloyloxyethyl isocyanate (Showa Denko K.K., Japan) was used as received. Milli-Q ultra-pure water was used in all the experimentsterm·mth.

Preparation of PRterm·dom cross-linkersterm·key (HPR-Cterm and iPR-Cterm) HPR or iPR (500 mg), the DBTDL catalyst (1 drop) and BHT (polymerization inhibitor, 0.78 mg) were dissolved in 30 ml of anhydrous DMSO. 2-Acryloyloxyethyl isocyanate (78 mg) was dissolved in 10 ml of anhydrous DMSO and the solution was added dropwise to the mixtures with vigorous stirring in the absence of light. The mixtures were then continuously stirred overnight at 40 °C to ensure that the reactions were complete. HPR-Cterm or iPR-Cterm was reprecipitated from the reaction mixture using an excess of methanol or acetone, respectively, and the precipitated product was refrigerated. The products were washed several times with methanol and acetone and then dried. The total number of vinyl groups per HPR and iPR was estimated from 1 H-NMR spectra and was found to be ca. 200 ( Supplementary Figs 1–3 ).

Preparation of hydrogelsterm·key The stretchable hydrogelsterm·key were prepared by conventional free-radical polymerization of the monomers with the PRterm·dom cross-linkersterm·key. For the polyelectrolyte hydrogelsterm·key, appropriate amounts of NIPAterm, AAcNaterm, HPR-Cterm or BISterm, and APS (initiator) were dissolved in water. The final concentrations of the ionic monomer and NIPAterm were 0.1 and 1.9 M, respectively, whereas the cross-linkerterm·key concentration changed. For the NIPAterm–iPR-Cterm hydrogelterm·key, appropriate amounts of NIPAterm, iPR-Cterm and APS were dissolved in water. The final concentration of NIPAterm monomer was 2 M, whereas the concentration of iPR-Cterm changed. In all the pre-gel solutions, the total concentration of the monomers excluding the cross-linkersterm·key was fixed at 2 M. Next, N 2 gas was bubbled through the pre-gel solutions for 30 min, which were then sonicated to remove excess nitrogen from the solution. The pre-gel solution was infused onto glass slides separated by Teflon spacers to prepare slab gels. Cylindrical gels were prepared using microcapillaries with an inner diameter of 270 μm. To initiate the polymerization below room temperature, a few drops of TEMED were added to the pre-gel solution. The gelations were performed at 4 °C for 24 h. The hydrogelsterm·key were thoroughly washed with water for 2 weeks to remove any unreacted monomer or reaction residue.

Mechanical strength tests The mechanical properties of the hydrogelsterm·key were measured with a TA Instruments RSA III rheometric solid analyser. The as-prepared 0.5-mm-thick hydrogelterm·key samples were cut into 5-mm × 30-mm rectangles for the stress–strain measurements. The hydrogelterm·key samples were placed and aligned between two fixtures and were tightly fixed by sample-loading bolt screws at both ends. We ensured that the hydrogelterm·key samples were smooth before each measurement. The transient strain-controlled multiple extension mode was used as the test set-up. The elongation rate was 0.1 mm s −1 . The measurements were conducted in air at room temperature (~25 °C). The reproducibility of the stress–strain curves was verified by successive measurements.

SAXSterm·mth SAXSterm·mth measurements were performed using the synchrotron radiation light source (beamlines BL-6A, BL-15A and BL-10C) at the Photon Factory, High Energy Accelerator Research Organization, KEK (Tsukuba, Japan). The wavelength λ of the X-ray beam was 1.50 Å, and the beam size was 0.7 mm (vertical) × 0.7 mm (horizontal). An X-ray charge-coupled device detector (C4880-50-26, Hamamatsu Photonics, Japan) equipped with a 150-mm diameter X-ray image intensifier was used as the SAXSterm·mth detector. The as-prepared 1-mm-thick hydrogelterm·key samples were cut into rectangles before they were analysed. The samples were placed in a uniaxial stretching machine for the deformation. The stretching direction of the hydrogelterm·key samples was vertical. The distance between the sample and the detector was ~2,300 mm, which was later calibrated according to the diffraction peaks of chicken tendon collagen (domain spacing, d =653 Å). The SAXSterm·mth patterns were recorded for 0.01 Å −1 < q <0.08 Å −1 , where q is the magnitude of the scattering vector and 2 q is the scattering angle. The typical exposure time was 30 s, where the scattering pattern did not change. Therefore, the beam damage and the drying of the gel were ignorable in this experimental condition.

Author contributions Y.T. designed the project. A.B.I., K.E., H.G. and Y.S. performed the experimentsterm·mth. All authors discussed the results and contributed to the data interpretation. Y.T., Y.S. and A.B.I. wrote the manuscript. Y.T., Y.S., A.B.I., K.I. and T.S. commented on the manuscript.

Additional information How to cite this article: Bin ImranpersName, A. et al. Extremely stretchable thermosensitiveterm·key hydrogelsterm·key by introducing slide-ring polyrotaxaneterm·dom cross-linkersterm·key and ionic groups into the polymer network. Nat. Commun. 5:5124 doi: 10.1038/ncomms6124 (2014).

Supplementary Material Supplementary Figures 1-6 and Supplementary Tables 1-3 Mechanical Properties of NIPA-AAcNa-BIS hydrogelterm·key Mechanical Properties of NIPA-AAcNa-HPR-C hydrogelterm·key Mechanical Properties of NIPA-iPR-C hydrogelterm·key Acknowledgments Y.T. acknowledges the support of Grants-in-Aid for Scientific Research (Nos 23245047 and 22107012) on the Innovative Area ‘Fusion Materials’ (area no. 2206) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT). Y.S. and K.I. acknowledge the support of a Grant-in-Aid for Scientific Research (S) (No. 20221005), and Y.S. acknowledges the support of a Grant-in-Aid for Young Scientists (B) (No. 22750199) from the Japan Society for the Promotion of Science (JSPS). The small-angle X-ray scatteringterm·mth experimentsterm·mth were performed at beamlines BL-6A, BL-15A and BL-10C at the Photon Factory, High Energy Accelerator Research Organization, KEK, with the approval of the Photon Factory Program Advisory Committee (proposal nos 2007G647, 2009G618, 2010G506 and 2011G578). N -Isopropylacrylamideterm and 2-acryloyloxyethyl isocyanate were kindly provided by Kohjin (Tokyo, Japan) and Showa Denko K.K. (Japan), respectively.

References Associated Data Supplementary Materials Supplementary Figures 1-6 and Supplementary Tables 1-3 Mechanical Properties of NIPA-AAcNa-BIS hydrogelterm·key Mechanical Properties of NIPA-AAcNa-HPR-C hydrogelterm·key Mechanical Properties of NIPA-iPR-C hydrogelterm·key