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# A universal method to easily design tough and stretchable hydrogels

## Abstract

Hydrogels are flexible materials that have high potential for use in various applications due to their unique properties. However, their applications are greatly restricted by the low mechanical performance caused by high water content and inhomogeneous networks. This paper reports a universal strategy for easily preparing hydrogels that are tough and stretchable without any special structures or complicated processes. Our strategy involves tuning the polymerization conditions to form networks with many polymer chain entanglements to achieve energy dissipation. Tough and stretchable hydrogels can be prepared by free radical polymerization with a high monomer concentration and low cross-linker content to optimize the balance between physical and chemical cross-links by entanglements and covalent bonds, respectively. The strategy of using polymer chain entanglements for energy dissipation allows us to overcome the limitation of low mechanical performance, which leads to the wide practical use of hydrogels.

## Introduction

Hydrogels are soft materials that consist of physically or chemically cross-linked polymer networks and a large quantity of water. Hydrogels have a high water content and low elastic modulus (~100 kPa) and exhibit stimulus-responsive behavior, similar to biological tissues; thus, hydrogels have many potential applications as biomaterials for drug delivery systems, biosensors, and cell culture1,2,3,4,5. Although hydrogels are soft and flexible, they are also weak and brittle6. Standard hydrogels can be easily broken when subjected to a sub-MPa tensile stress or large deformation. The fracture energy of hydrogels is only approximately one hundredth that of biological tissues such as cartilage7,8. Recently, to overcome the low mechanical properties of hydrogels, some researchers have strategically designed network structures of hydrogels, such as sliding-ring hydrogels9,10, nanocomposite hydrogels11, double network (DN) hydrogels12,13,14, and other structures15,16,17,18,19,20,21,22. DN hydrogels, which consist of a densely cross-linked and brittle polyelectrolyte 1st network and a sparsely cross-linked and ductile neutral 2nd network, exhibit high mechanical strength (tensile fracture stress of ~10 MPa and tensile fracture strain of 1000–2000%) and toughness (fracture energy of ~4000 J m−2)13,14. The superior mechanical properties of DN hydrogels are attributed to energy dissipation through the internal fracture of the brittle 1st network. In addition, dynamic cross-links that reversibly dissociate and form in response to stimuli such as temperature, molecules, and stress are useful tools for designing not only responsive hydrogels but also tough hydrogels23,24,25,26,27,28. The abovementioned studies suggest that structural design is required to achieve effective energy dissipation in hydrogels.

## Materials and methods

### Materials

Acrylamide (AAm), N,N-methylenebisacrylamide (MBAA), N,N,N,N-tetamethylethylenediamine (TEMED), and ammonium persulfate (APS) were purchased from Wako Pure Chemical Industries (Wako, Japan). 2-(Methacryloyloxy)ethyl phosphorylcholine (MPC) was supplied by NOF Corporation (Tokyo, Japan).

### Synthesis of poly(acrylamide) (PAAm) hydrogels

AAm, which was recrystallized from benzene prior to use, MBAA as a cross-linker, and TEMED were dissolved in deionized water to prepare a monomer solution with a total volume of 2.42 mL. In deionized water, APS, as an initiator, was also dissolved. The aqueous monomer and APS solutions were degassed using freeze-pump-thaw cycles and purged with Ar. After the freeze-pump-thaw cycles, the aqueous APS solution (0.08 mL) was added to the monomer solution in an ice bath to prevent premature gelation. The resulting mixture containing APS and TEMED in concentrations of 0.47 × 10−3 mol/L and 4.0 × 10−3 mol/L, respectively, was poured into a mold composed of two slides separated with a 5-mm-thick glass spacer (for compression tests) or a 1.76-mm-thick glass spacer (for tensile tests) (Fig. S1). The copolymerization of AAm and MBAA was performed at 25 °C for 1 day. As-prepared PAAm hydrogels were obtained by removing the molds. Swollen PAAm hydrogels were prepared by immersing the as-prepared hydrogels in water until their swelling ratio reached equilibrium.

### Synthesis of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) hydrogels

MPC as the main monomer, MBAA as a cross-linker, and TEMED were dissolved in deionized water to prepare a monomer solution with a total volume of 0.92 mL. APS, as an initiator, was dissolved in deionized water to prepare an initiator solution. The aqueous monomer and initiator solutions were degassed using six freeze-pump-thaw cycles and purged with Ar. After the freeze-pump-thaw cycles, the aqueous APS solution (0.08 mL) was added to the monomer solution in an ice bath to prevent premature gelation. The resulting mixture of APS and TEMED at concentrations of 0.47 × 10−3 mol/L and 4.0 × 10−3 mol/L, respectively, was poured into a mold composed of two slides separated with a 5-mm-thick glass spacer (for compression tests) or a 1.76-mm-thick glass spacer (for tensile tests) (Fig. S1); copolymerization of MPC and MBAA was performed at 25 °C for 1 day. As-prepared PMPC hydrogels were obtained by removing the molds.

### Conversion measurements

The as-prepared PAAm hydrogels were washed by immersion in deionized water for 2 weeks to completely remove unreacted monomers and initiators. Then, after the PAAm gels were dried at 70 °C in an oven for 2 days, their weight (Wdried gel) was measured. Wdried gel represents the total weight of polymerized AAm and MBAA in the resulting PAAm networks. The conversion of the monomers after gel formation was determined from the Wdried gel and the total weight (Wmonomer) of AAm and MBAA in a feed solution using Eq. (1).

$${\mathrm{Conversion}}\,({\mathrm{\% }}) = \frac{{W_{drie\,gel}}}{{W_{monomer}}} \times 100$$
(1)

### Measurement of the water content of the hydrogels

PAAm hydrogels were immersed in deionized water until their swelling ratio reached equilibrium. Then, the weight (Wswollen gel) of the swollen hydrogels was measured. After they were dried at 70 °C in an oven for 2 days, the weight (Wdried gel) of the resulting dried gels was measured. The equilibrium water content of the PAAm hydrogels was determined using Eq. (2).

$$Water\,content\,({\mathrm{\% }}) = \frac{{W_{swollen\,gel} - W_{dried\,gel}}}{{W_{swollen\,gel}}} \times 100$$
(2)

### Mechanical tests

Compression tests of the as-prepared and swollen PAAm and PMPC hydrogels, which were prepared using the molds shown in Fig. S1, were performed using a mechanical testing instrument (SMT1-2-N, Shimadzu Co. Ltd., Kyoto) with a compression velocity of 10 mm/min−1. Tensile tests of the as-prepared and swollen PAAm and PMPC hydrogels were performed using a mechanical testing instrument with crosshead speeds of 5, 50, and 500 mm/min−1. The toughness of the hydrogels, which is the work to fracture, was determined from the area under the tensile stress–strain curve of an unnotched sample with a length of 20 mm.

### Determination of the cross-linking density of the hydrogels

The elastic modulus of the hydrogels was determined from the strain-stress curves obtained by the compression tests using Eq. (3).

$$\sigma = G\left( {\alpha - \alpha ^{ - 2}} \right)$$
(3)

where σ is the compression stress, G is the elastic modulus, and α is the ratio of the thickness of the gel before and after compression. The plot of σ vs. (αα−2) showed a linear relationship. The slope of this line provided the G value. The effective cross-linking density, νe, of the gel was determined by Eq. (4).

$$G \approx RT\nu _e\phi ^{1/3}$$
(4)

### Dynamic mechanical analysis

Dynamic mechanical analysis of the hydrogels was conducted using a nonresonance forced vibration viscoelastometer (Rheogel-E-4000F; UBM, Kyoto, Japan) in tension mode. The frequency and amplitude of the vibration were adjusted to 100 Hz and 50 μm, respectively. From the dynamic mechanical analysis, we determined the storage modulus (G′), loss modulus (G″) and loss factor (tanδ = G″/G′) to evaluate the viscoelastic properties of the hydrogels prepared under various conditions.

## Results and discussion

### Mechanical properties of PAAm hydrogels

First, to design polymer networks with many entanglements and a minute number of chemical cross-links, we prepared PAAm hydrogels, which are the most standard hydrogels, by the copolymerization of AAm as the main monomer and MBAA as a standard cross-linker using a wide range of monomer concentrations and cross-linker contents. The mechanical properties of the as-prepared PAAm hydrogels synthesized with various monomer concentrations and cross-linker contents were evaluated by compression and tensile tests (Fig. 2). Polymerization with high monomer concentrations (2.5 mol/L and 5.0 mol/L) allowed self-standing PAAm hydrogels with a cross-linker content of 0.001 mol% to form despite the low cross-linker content. As-prepared PAAm hydrogels with a cross-linker content greater than 0.1 mol% easily broke during compression (Fig. 2a–d and Movie S1b). However, the as-prepared PAAm hydrogels with a cross-linker content lower than 0.1 mol% did not break at up to 95% strain and 6-MPa stress (Fig. 2c and Movie S1a). From the work of Sakai et al.31, the stress–strain curve of a four-arm poly(ethylene glycol) (tetra-PEG) hydrogel is replotted in Fig. 2a–c. The as-prepared tetra-PEG hydrogel is tough owing to its homogeneous network structure. Notably, although standard free radical polymerization results in the formation of an inhomogeneous network structure30, the as-prepared PAAm hydrogels prepared under polymerization conditions with a high monomer concentration and a low cross-linker content were tougher than the tetra-PEG hydrogel with a homogeneous network structure.

Some papers have reported that as-prepared hydrogels designed using unique strategies exhibit high toughness; however, most of them do not exhibit the mechanical properties of swollen hydrogels after equilibrium swelling in aqueous media. In addition, the mechanical properties of swollen hydrogels are important because these hydrogels are typically utilized in aqueous media. Compression and tensile tests of swollen PAAm hydrogels demonstrated that their fracture strain and stress decreased after equilibrium swelling in aqueous media. The water content of the swollen PAAm hydrogels after equilibrium swelling decreased with increasing cross-linker content (Fig. S2). It should be noted that the swollen PAAm hydrogels prepared with a higher AAm concentration had a lower water content than those prepared with a lower AAm concentration even though they were prepared with the same cross-linker content. This means that polymerization with high monomer concentrations is likely to induce polymer chain entanglements in the resulting hydrogel networks. The decreased fracture stress and strain of swollen hydrogels are caused by an increase in the water content (Fig. S3). Because polymer chains are expanded in swollen hydrogels, they cannot be expanded further by applying stress. In addition, entanglements as physical cross-links are partially loosened during the swelling of hydrogels in aqueous media. Thus, swollen hydrogels break under a smaller strain than the as-prepared hydrogels because the applied stress is not effectively dissipated. However, the swollen PAAm hydrogels prepared under polymerization conditions of a high monomer concentration and low cross-linker content retain their high toughness despite equilibrium swelling (Figs. S2 and S3). For the swollen hydrogels with a 0.005 mol% cross-linker content, even if a large strain of more than 90% is applied during compression tests or a large elongation of more than seven times is applied during tensile tests, these hydrogels do not fracture despite the high water content of more than 90%, and they recover to their original shape after the stress is released (Fig. 2h, Figs. S2, S3 and Movie S3a). Of note, the swollen hydrogels prepared with a monomer concentration of 5.0 mol% and a cross-linker content of 0.005 mol% cannot be cut with a knife despite their swollen state (Fig. 2h and Movie S3b). Thus, the as-prepared and swollen PAAm hydrogels prepared with a high monomer concentration and a low cross-linker content demonstrate high mechanical toughness and high stretchability.

### Relationship between the cross-linked structure and toughness of PAAm hydrogels

To elucidate the mechanism by which hydrogels become tough and stretchable, we determined the toughness of PAAm hydrogels from the stress–strain curve during tensile tests. In general, the fracture energies of polymeric materials are determined from the stress–strain curve of notched samples6,32,33. However, we were not able to notch the PAAm hydrogels synthesized in this study because they were very tough. In this study, we defined toughness from the area under the tensile stress–strain curve of an unnotched sample. The toughness is larger than the fracture energy determined using a notched sample because it includes energies not only for growing cracks but also for notching. The PAAm hydrogels prepared with a cross-linker content of more than 0.1 mol% have a much lower toughness than those prepared with a cross-linker content less than 0.1 mol% (Fig. 3a). An increase in the monomer content during the polymerization considerably enhanced the toughness of the resulting hydrogels. Of note, the PAAm hydrogel prepared with a monomer concentration of 5.0 mol/L and a cross-linker concentration of 0.005 mol% exhibited the maximum toughness of 1.6 MJ/m3, although the toughness could not be directly compared with the fracture energy of tough hydrogels prepared by different strategies13,15,33,34.

## Conclusion

In summary, we have demonstrated a simple and versatile strategy for producing tough and stretchable hydrogels by free radical polymerization of standard hydrophilic monomers. Our strategy is to only tune the polymerization conditions without introducing a special structure or using complicated methods; we can optimize the network structures, which have many polymer chain entanglements for energy dissipation by polymerization conditions with a high monomer concentration and a low cross-linker content. The hydrogels prepared under the optimized conditions have a νexp/νtheo ratio greater than one, indicating that the hydrogels contain physical cross-links based on polymer chain entanglements in addition to chemical cross-links based on MBAA. The toughness of the hydrogels increased considerably with an increase in νexp/νtheo above than one. Although our strategy uses neither a special structure nor a complicated method, the hydrogels prepared using our strategy exhibited high toughness. Tough and stretchable nonionic PAAm and zwitterionic PMPC prepared under optimized polymerization conditions undergo large elongations, exhibit high fracture strain and cannot be cut with a knife because of the many entanglements as physical cross-links. Our strategy is applicable to preparing tough and stretchable hydrogels from a variety of polymers. Structural design using polymer chain entanglements for energy dissipation to overcome the limitation of low mechanical performance will lead to many practical uses of hydrogels.

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## Acknowledgements

This work was supported in part by a Grant-in-Aid for Scientific Research (B) (No. JP20H04539) from the Japan Society of the Promotion of Science (JSPS); by a Grant-in-Aid for Scientific Research on Innovative Areas of “Aquatic Functional Materials” (No. JP20H05236) and the Private University Research Branding Project: Matching Fund Subsidy from Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan (2016–2020); by the AMED S-innovation Program for the development of biofunctional materials for the realization of innovative medicine; and by research grants from the Canon Foundation.

## Author information

Authors

### Contributions

T.M. conceived the idea, designed the experiments, and supervised the project. C.N., Y.I., and C.H. performed experiments. All authors discussed the results and contributed to the data interpretation. C.N. and T.M. wrote the manuscript. T.M. edited and revised the manuscript.

### Corresponding author

Correspondence to Takashi Miyata.

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### Conflict of interest

The authors declare no competing interests.

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Norioka, C., Inamoto, Y., Hajime, C. et al. A universal method to easily design tough and stretchable hydrogels. NPG Asia Mater 13, 34 (2021). https://doi.org/10.1038/s41427-021-00302-2