High Strength Astringent Hydrogels Using Protein ... - ACS Publications

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High Strength Astringent Hydrogels Using Protein as the Building Block for Physically Cross-linked Multi-Network Rongnian Xu,†,‡,§ Shuanhong Ma,†,‡ Peng Lin,‡ Bo Yu,‡ Feng Zhou,*,‡ and Weimin Liu*,‡ ‡

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China § College of Materilas Science and Opto-Electonic Technology, University of Chinese Academy of Sciences, Beijing 100049, China S Supporting Information *

ABSTRACT: Integrating proteins into a hydrogel network enables its good bioactivity as an ECM environment in biorelative applications. Although extensive studies on preparing protein hydrogels have been carried out, the reported systems commonly present very low mechanical strength and weak water-rentention capacity. Learning from the astringent mouthfeel, we report here a protein engineered multinetwork physical hydrogel as TA-PVA/BSA. In a typical case, the BSA protein-integrated poly(vinyl alcohol) (PVA) solution is treated by the freeze-thaw method and forms the first hydrogel network, and tannic acid (TA) then cross-links with BSA proteins and PVA chains to form the secondary hydrogel network based on the noncovalent interaction (hydrogen bond and hydrophobic interaction). The as-prepared TAPVA/BSA composite hydrogel is a pure physically cross-linking network and possesses ultrahigh tensile strength up to ∼9.5 MPa but is adjustable, relying on the concentration of TA and BSA. Moreover, its mechanical strength is further improved by prestretching induced anisotropy of mechanical performance. Because of its controllable and layered structure as skin, the composite hydrogel presents good water-retention capacity compared to traditional high strength hydrogels. This work demonstrates a novel method to design high mechanical strength but layered physical cross-linking hydrogels and enables us to realize their biorelative applications. KEYWORDS: high strength hydrogel, astringent, tannic acid, protein/PVA, noncovalent interaction

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INTRODUCTION Hydrogels are typical “soft and wet” materials with threedimensional cross-linked network structure.1 Because of their responsive features to external stimuli including temperature,2 pH,3 light,4,5 electric field,6,7 magnetic field,8 etc., hydrogels are widely studied as promising smart materials for sensors,9,10 actuators,11 and drug delivery systems.12 The highly hydrated nature resembling the natural extracellular matrix (ECM), which is generally composed of highly hydrated biomacromolecular network, makes synthetic hydrogels the ideal artificial substitutes as tissues/organs, including skins,13 cartilage,14 muscles,15,16 blood vessels,16 cells,17 and so on. However, the synthetic hydrogels always demonstrate poor mechanical strength far beyond the requirement for tissue engineering. Great efforts have been taken in developing stiff and tough hydrogels to solve this predicament by introducing different energy dissipation mechanisms and novel structural design to generate tough hydrogels,18−20 such as double-network hydrogels,21,22 nanocomposite hydrogels,23−26 polyampholyte hydrogels,27 hydrogen-bonding hydrogels28,29 etc. Among them, the double network (DN) hydrogels, proposed first by Gong et al.,21 represent a good way to achieve the goal. DN hydrogels usually consists of a physically or chemically cross-linked © XXXX American Chemical Society

primary network and a secondary network formed by covalent bonds,20 ionic interaction,30,31 electrostatic interaction,32 hydrogen bonds,22 hydrophobic interaction,33,34 host−guest interaction,35 etc. For example, a dual-cross-linked (chemically cross-linking and carboxylic-Fe3+ complexation interaction) hydrogel can achieve tensile strength of 6 MPa36 and of ∼40 MPa by a prestretching process.37 Despite of high mechanical strength, those synthetic hydrogels are usually prepared from a limited number of vinyl monomers and their bioactivity are still worth verification. To improve the biocompatibility of high strength hydrogels for potential tissue engineering applications, biocompatible macromolecules (such as agarose,22 sodium alginate,30 cellulose,38 chitosan,39 carrageenan,40 and even DNA29) have been used to construct bioactive DN hydrogels. Meanwhile, integrating the proteins (extracted from natural sources or artificial proteins) into the three-dimensional gel Special Issue: 10 Years of Polydopamine: Current Status and Future Directions Received: March 26, 2017 Accepted: July 31, 2017

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DOI: 10.1021/acsami.7b04290 ACS Appl. Mater. Interfaces XXXX, XXX, XXX−XXX

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Moreover, different from the traditional systems of highstrength hydrogels, the TA-PVA/BSA hydrogel presents inhomogeneity of the layered structure and shows excellent water-retention capacity as natural skin.

network with special complex mechanisms results in the formation of protein-based biohydrogels.41 Such a kind of protein-based hydrogels is highly bioactive with similar property as ECM environment, and can be used as potential candidate for biomedical application and tissue replacement.42 However, again, the protein engineered hydrogels usually have very low mechanical strength, although the mechanical property of protein-incorporated hydrogel could be enhanced by increasing the molecular weight and concentration of PVA.43 So, up to now, engineering a protein-based hydrogel with high mechanical strength has been a huge challenge. Moreover, singly improving the mechanical strength of hydrogels is always at the expense of decreasing the pore size of the gel network, which in turn results in poor water content and water-retention capacity. One disadvantage in current high strength hydrogels system is its fast evaporation of network water molecules in nonliquid environment; this can not meet the requirement of its special biorelated applications, such as artificial skin and sensor (the hydrogel layer always need to be well-packaged and to prevent the water from evaporating).44 Up to now, this problem has long been ignored. However, nature makes up this limiation by its wonderful design of nonuniform structure. For example, our skin possesses a layered structure;45 its inside is wet matrix tissue, whereas the outside is dense cuticle that can prevent water from evaporating. Inspired, can we engineer high-strength proteinbased hydrogels with excellent water-retention capacity? Phenols and polyphenols compounds are widely existed in unripe fruits, plant tissues and vegetables, where they play important roles to biological functions.46,47 Among them, tannic acid (TA) with high content of dihydroxyphenyl (catechol) and trihydroxyphenyl (gallic acid, GA) anchor groups in its molecule structure has attracted great attention in surface engineering.48,49 In addtion, the extensive distribution of phenolic hydroxyl in TA enables to its easy coupling with other materials by noncovalent interaction, such as ioncoordination, hydrogen bond, and hydrophobic interaction. For example, TA has been successfully used for the preparation of functional hydrogels50−53 and implies potential application in tissue engineering.54 Previous studies indicated TA can also complex with biomacromolecule as proteins and induce its flocculation. The interaction mechanism between them is based on hydrophobic interaction and hydrogen bond.55 Such a mechanism has been successfully used to improve the mechanical strength of materials in the leather industry. In addtion, it is reported that astringent mouthfeel also comes from the strong interaction between tannic acid type of phenolic compounds and oral mucoproteins.56 Inspired, can we use the polyphenols chemistry to engineer high-strength protein-based hydrogels with excellent water-retention capacity? In this study, we try to make high-mechanical-strength proteins hydrogels by using the noncovalent interaction of TAprotein and TA-PVA to improve the strength of pure PVA hydrogel network. In typical case, we incorporated bovine serum albumin (BSA) into a physically cross-linked poly(vinyl alcohol) (PVA) network to form a proteinaceous PVA/BSA hydrogel, which is further strengthened by tannic acid (TA) through strong noncovalent interaction with both PVA ploymer chains and BSA. The as-prepared TA-PVA/BSA composite hydrogel is a pure physically cross-linking network, and possesses ultrahigh tensile strength up to ∼9.5 MPa, but is adjustable, relying on the concentration of TA and BSA.

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EXPERIMENTAL SECTION

Materials. Poly(vinyl alcohol) (PVA) was purchased from Shanghai City Sinopharm Chemical Reagent Co., Ltd. (Mw: 1750 ± 50, n ≈ 44, 99.9%). Tannic acid (TA) was provided by Beijing Yinuokai Technology Co., Ltd. and stored in a dark environment (Mw: 1701.23, 99%). Bovine serum (BSA) was purchased from Shanghai Aladdin Reagent Co., Ltd. All the chemicals were used without further purification. The distilled water was prepared with a pure Infinity system. Preparation of TA-PVA/BSA Hydrogels. First we prepared the PVA/BSA hydrogel, and then made it into TA-PVA/BSA hydrogel. The PVA/BSA hydrogel was prepared by a freeze−thaw process from a precursor mixture solution of poly(vinyl alcohol) (PVA) and bovine serum (BSA). Typically, 14 g of PVA powders was added into 100 mL of distilled water and then heated to 100 °C for 2 h until the powders completely dissolving; 0.5 g of BSA was added into a 100 mL centrifuge tube, then dissolved it with distilled water and added to the calibration line. After PVA solution was cooled to room temperature, 100 mL of BSA solution (5 mg/mL) was added into it. The mixture solution was then stirred, followed by degassing. Finally, the mixture solution was poured into the mold (PTFE board used as two contact surfaces) and sealed up in freeze-drying machine at −40 °C for 2 h. After thawing at room temperature, the initial hydrogel was sealed again in a freeze-drying machine at −40 °C for 2 h. We obtained the PVA/BSA hydrogel after getting through 3 cycles of the freeze−thaw process. Five grams of TA was added into 95 mL of distilled water (5%). The TA-PVA/BSA hydrogel was prepared by soaking PVA/BSA hydrogel into TA solution (5%) for 2 days in dark environment. When the TA mass fraction is controlled, the concentration of BSA is 5.0 mg/mL; When the BSA mass concentration is controlled, the TA mass fraction is 5%; the thickness is 0.5 mm when the immersing time is controlled, and the immersing time is 48 h when the thickness is controlled. Preparation of Prestretched TA-PVA/BSA Hydrogels. The PVA/BSA hydrogels were prepared by the above method and cut into rectangular shapes, and the cut PVA/BSA hydrogels were then fixed with 3D printed molds and stretched to a certain strain (100, 120, 150, and 180%), and finally immersed them into TA (5%) solution for 2 days. Mechanical Property Measurement. The test samples were cut into rectangular shapes. The machine is an electrical universal material testing machine with a 500 N load cell (EZ-Test, SHIMADZU). The crosshead velocity was kept at 100 mm/min for tensile measurement. The elastic modulus was calculated from the slope 5−15% of strain ratio of the stress−strain curve. The shear tearing test was performed in the same machine with a tensile velocity of 100 mm/min. In typical case, two pieces of PVA/BSA hydrogel samples were stacked with different contact areas and then immersed them into 5% TA solution. After 48 h, the shear tearing test was performed to separate the overlapping part of two hydrogel pieces. The compression test was performed by load−unload mode with a compression velocity of 50 mm/min and compression strain of 70%. Morphology Characterization. The samples morphologies were characterized on field-emission scanning electron microscope (FESEM) (JSM-6701F, JEOL Inc., Japan) at an accelerating voltage of 5 kV. The test samples were prepared according to the standardized process. The test samples were frozen with liquid nitrogen or by an automatic refrigeration system and were then dried in the freezedrying machine for 24 h at a vacuum degree of 5 Pa (SCIENTZ-10 N, Ningbo Scienzt Biotechnology Co., Ltd.). B


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Scheme 1. Preparation of TA-PVA/BSA Hydrogel and Possible Formation Mechanisms Involving Hydrogen Bonds and Hydrophobic Interaction

Figure 1. (a) Tensile stress−strain curves of PVA hydrogel, PVA/BSA (5 mg/mL) hydrogel, and TA(5%)-PVA/BSA(5 mg/mL) hydrogel and (b) corresponding elastic modulus.

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1695 cm−1 and 1600, 1440, 1520 cm−1 (phenyl) were also observed, which further showed successful preparation of the TA-PVA/BSA hydrogel. The XRD results indicate that the TA cross-link did not eliminate the original crystallization of PVA chains (Figure S2), which reveals that the TA-PVA/BSA hydrogel is a typical multinetwork. Detailed procedures are given in the Experimental Section. Figure 1a are the typical stress−strain curves of PVA hydrogel, PVA/BSA hydrogel, and TA-PVA/BSA hydrogel. It can be seen that the tensile stress of pure PVA hydrogel (Mw=1750 ± 50) is only about 110 KPa at the strain of 160%. After adding the BSA, the tensile stress and strain of the prepared PVA/BSA hydrogel decreased slightly in comparison with pure PVA hydrogel. This indicated that the addition of BSA proteins will more or less affect the crystal degree of PVA molecular chains. After treating with TA, the tensile stress of the prepared TA(5%)-PVA/BSA hydrogel can achieve ∼3 MPa, which is ∼27 times higher than pure PVA hydrogel, and the corresponding fracture strain increases to 470%. So the asprepared TA-PVA/BSA hydrogel demonstrates very good mechanical property. As shown in snap (Figure 1a), one piece of TA(5%)-PVA/BSA hydrogel can easily lift up a steel block with weight of 483 g. The corresponding elastic modulus are shown in Figure 1b. The elastic modulus of pure PVA

RESULTS AND DISCUSSION The preparation of the TA-PVA/BSA composite hydrogel and its interaction mechanism are briefly demonstrated in Scheme 1. First, the PVA/BSA hydrogel was prepared by cycle freezingthawing process from the mixture of PVA and BSA. Then the PVA/BSA hydrogel was immersed into TA solution for constructing the new network, which results in the formation of tough TA-PVA/BSA hydrogel after removing excessive TA in deionized water for 48 h and allowed for swelling equilibrium. In typical case, the formation of new network includes two kinds of interactions: hydrogen bonds between the phenol hydroxyl in TA molecules and alcohol hydroxyl in crystallized PVA chains,57 and the hydrogen bonding and hydrophobic interaction between TA and BSA protein.55,58 The chemical components of the hydrogels were verified by Fouriertransform infrared spectroscopy (FTIR), as illustrated in Figure S1. The peak appeared at 3263 (−OH), 1656, 1590 cm−1, and 2938, 2909, 2853 cm−1(−CH3, −CH2−) is characteristic vibration peak of the pure PVA hydrogel. The new vibration peak appeared at 1545 cm−1 showed the successful mixture of BSA into PVA hydrogel. After treating with TA, the −OH peak shifted to a lower wavenumber of 3220 cm−1, which is attributed to the formation of strong hydrogen bonding between PVA/BSA and TA. Moreover, the new peaks at C


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Figure 2. (a) Tensile stress−strain curves of TA-PVA/BSA (5 mg/mL) hydrogels with different TA mass fraction for 48h treatment. (b) Tensile stress−strain curves of TA(5%)-PVA/BSA hydrogels with different BSA mass concentration for 48 h TA treatment. (c) The tensile stress of TA(5%)-PVA/BSA (5 mg/mL) hydrogels with different soaking time in TA; (d) the tensile stress of TA(5%)-PVA/BSA (5 mg/mL) hydrogels with different thickness soaking in TA for 48 h. (The thickness of PVA/BSA hydrogel for TA treatment in isa−c is 0.8 mm, the strip width is ∼6 mm.).

hydrogel is ∼0.02 MPa, slightly increases to ∼0.03 MPa of the PVA/BSA hydrogel, and sharply to 0.43 MPa of the TA-PVA/ BSA hydrogel. These data intuitively demonstrate the significant role of the nonvovalent interaction between TA and BSA/PVA in enhancing the mechanical strength of the hydrogel. Obviously, the as-prepared TA-PVA/BSA composite hydrogel is a purely physical cross-linking network, and its mechanical strength is completely accumulated by noncovalent interactions. The mechanical strength of the TA-PVA/BSA hydrogel can be well adjustable. In typical experiment, the mass concentration (Cm) of BSA and TA, the soaking time (t) in TA and thickness (h) of the PVA/BSA hydrogel sheets can all affect the mechanical strength of the hydrogel. Keeping the Cm of BSA (5 mg/mL) as constant, the effect of Cm (TA) on tensile stress and strain is given in Figure 2a. It is seen that as the Cm of TA increases from 0 to 5%, the tensile stress of TA-PVA/BSA (BSA: 5 mg/mL) hydrogel improves gradually from 0.02 to 3.0 MPa, whereas the strain also increases from 160 to 470%. Keeping the Cm of TA (5%) as constant, the effect of Cm of BSA on mechanical strength of TA-PVA/BSA hydrogel was also investigated and the result was shown in Figure 2b. As the Cm of BSA increases from 0 to 5 mg/mL, the tensile stress of the TA-PVA/BSA hydrogel increases gradually from 0.6 to 3.0 MPa, whereas the strain increases from 410 to 470%. Compared with pure PVA hydrogel (tensile stress 110 Kpa and strain 160%), the treatment of it (without BSA) with TA can increase the tensile stress to 0.5 MPa and strain to 410%, indicating noncovalent interaction also occurs between PVA chains and TA.29 Adding more BSA in the polymer network creates more cross-linking points so that dramatically increases the mechanical strength. It is hypothesized that TA may interact with a single protein and a single TA molecule may link different proteins or link protein with PVA chains. The water

content of the TA-PVA/BSA hydrogels was measured and is given in Figure S3. The lowered water content of each sample after treatment with TA indicates that the interaction between hydrogel and TA shrinks the pore size of the hydrogel network effectively. The more the interaction, the lower the water content is. The tensile stress of the hydrogels increases linearly upon extending the soaking time of PVA/BSA hydrogel (strip thickness: 0.8 mm) in TA (5%) solution (Figure 2c). When immersed for 48 h, the tensile stress and strain of the hydrogels achieved the maximum. Further extending the soaking time to 6 days, the strain decreases obviously, whereas the stress almost kept unchanged (Figure S5). The decreased strain can be attributed to the plastic transition of hydrogel materials due to overwhelming noncovalent cross-linking between TA and PVA/BSA. After immersing into TA solution for 6, 12, to 48 h, the thickness of the hydrogel decreases from 0.8 mm (original thickness) to 0.38, 0.318, and 0.224 mm (Figure S5). Correspondingly, their volume shrinks to its original 47.5%, 39.7% and 28%. Meanwhile, the longer the immersing time, the lower the water content. As shown in Figure 2d, keeping the same Cm of BSA (5 mg/mL) and TA (5%), the relationship between stress and thickness is negatively correlated. The 2.2 mm thick hydrogel has the lowest strength of 0.58 MPa, whereas 0.5 mm thick hydrogel has the highest strength of 3.46 MPa (Figure 2d). Upon immersing into the TA solution, the outmost layer of the PVA/BSA hydrogel will preferentially contact with TA molecules, resulting in a nonuniform enhancement of the network strength. Once dense TA-PVA/ BSA layer is formed, it is difficult for TA molecules to diffuse into the inner network of PVA/BSA hydrogel. This means that the thinner the PVA/BSA hydrogel, the higher tensile strength the as-prepared TA-PVA/BSA has. The mechanical property must be closely related with the microstructures of hydrogels. After freeze−dry cycles, the D


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Figure 3. (a) Surface morphology of PVA hydrogel; (b) surface morphology of PVA/BSA(5 mg/mL) hydrogel; (c) surface morphology of TA(5%)PVA/BSA(5 mg/mL) hydrogel; (d) cross-sectional morphology of PVA hydrogel; (e) cross-sectional morphology of PVA/BSA(5 mg/mL) hydrogel; (f) cross-sectional morphology of TA(5%)-PVA/BSA(5 mg/mL) hydrogel.

Figure 4. (left) Schematic diagram of shear tearing experiment to measure complextion interaction between TA and PVA/BSA, (right) the total and per unit area tearing force of two overlapped PVA/BSA (5 mg/mL) hydrogel pieces Vs contact area. (Two pieces of samples were stacked with different contact areas and then immersed them into 5% TA solution. After 48 h, the shear tearing force to separate the hydrogel pieces was measured.)

morphology of hydrogels samples was observed by fieldemission scanning electron microscopy (FESEM). As shown in Figure 3a, d, both the surface and cross-section of pure PVA hydrogel show a three-dimensional porous network structure. After adding BSA proteins, PVA/BSA still shows a highly porous structure, but the network structure changes obviously, in which fibrillar structure is obvious and uniformly distributed across the entire PVA/BSA hydrogel (Figure 3b and Figure 3e). These cavities must come from water evaporation (note these two samples have greater than 90% water content.). Addition of BSA may affect its crystalline phase, resulting in a more fibrillar structure. After being immersed into TA solution, the resultant TA-PVA/BSA hydrogel displays highly compact structure both on surface (Figure 3c) and cross-section (Figure 3f), implying strong intermolecular interaction occurs and drives close the interchain distance. Such strong noncovalent interaction between TA and PVA/ BSA was quantitatively measured by separating two stacked strips of PVA/BSA hydrogel after treated with 5% TA for 48 h. In typical case, the lap shear tearing force to separate two strips is equivalent to the weak interaction force between TA and PVA/BSA. As shown in Figure 4, the lap shear tearing force to separate the two pieces increases almost linearly with the

overlap contact area, indicating that weak interaction is sufficient and effective among polymer chains. However, the calculated force per unit area keeps a constant (0.1 ± 0.05 N/ mm2) value. By comparison, it is found that the lap shear tearing force value per unit area is highly larger than the mean shear adhesive force (0.1517 ± 0.015 N/cm2) of wetted toe pad reported in literature,59 which indicates the complexation interaction is relatively strong. So the tearing test well proves that strong interaction occurs between TA and PVA/BSA. Very interestedly, such interaction can be used to adhere two cutted PVA/BSA hydrogel pieces together (Figure 5a). One possible mechanism is that TA molecules interact with unsaturated hydrogen forming groups in section and then link two hydrogel pieces together. In a typical case, the PVA/BSA hydrogel was cut into two pieces and then dropped the TA solution at fracture interface, two pieces of hydrogels will adhere together quickly. After 48 h, the fracture surfaces were healed and the healed hydrogel could be stretched to approximate 1.5 times that original length without breaking out and can even load a 20 g weight (Figure 5b). Such a healing mechanism can be further proved by the morphology observation in SEM. As shown in Figure 5c, the cutting line almost can not be seen and two surfaces heal together. On the basis of such a noncovalent E


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shown in Figure 6b, in the parallel direction it demonstrates a little bit higher tensile stress than that of the vertical direction, whereas in the vertical direction obviously it possesses higher strain and better elasticity. The structural inhomogeneity and mechanical toughness are also normally seen in natural tissue organs including cartilage,60 muscle61 and skins.62 Besides, the hydrogel materials should have a good water maintenance. So far, not a single hydrogel can really mimic the natural samples. However, the water maintenance of most hydrogels is low (the gel losses water quickly). Liu et al. created superhydrophobicity on the hydrogel surface to tune the permeability of small molecules.63 The astringent interaction between PVA/BSA hydrogel and TA is time-dependent, and low TA concentration or short immersion time leads to incomplete interaction between TA and PVA/ BSA, resulting in an inhomogeneous network structure where the outer shell has dense structure and rigidity but the interior has good elasticity and high water content. Such layered distribution of hydrogel largely delays the loss of network water, similar to the skin structure. To prove that, we prepared two hydrogel cylinders of pure PVA hydrogel and TA-PVA/ BSA hydrogel (the thickness of the outmost PVA/BSA/TA layer is ∼0.5 mm). The two hydrogel cylinders were saturated in water and then transferred to an oven at 50 °C. The water loss was recorded at different heating time. As shown in Figure 7a, the weights of two kinds of hydrogel cylinders decreases gradually with extending the heating time due to water evaporation. TA-PVA/BSA hydrogel cylinder shows obviously slower water loss rate than pure PVA hydrogel cylinder. Typically, after 22 h, the weight percentage of pure PVA hydrogel cylinder is only 15% whereas the TA-PVA/BSA hydrogel cylinder is still as high as 40%. This means that the asprepared TA-PVA/BSA hydrogel possesses excellent better water loss-resistance property. As shown in Figure 7b, the pure PVA hydrogel cylinder demonstrates obvious volume shrinkage, whereas TA-PVA/BSA hydrogel cylinder only shows slight volume shrinkage. Furthermore, it was found that the TA-PVA/ BSA hydrogel cylinder still possesses good elasticity after 22 h at 50 °C. As shown in Figure 7c, upon compression to 70%, the heated TA-PVA/BSA hydrogel cylinder can almost recover to the original state. This can be further proved by the load-unload compression curve (Figure S6).

Figure 5. (a) The schematic diagram of TA solution assisted healing process of two PVA/BSA hydrogel pieces; (b) the visual demonstration experiment of healing; (c) the SEM image showing healing interface.

mechanism, our result provides a novel design strategy for developing high strength hydrogel system with liquid assisted self-adhesion or healing property in wet environment. To maximize the intermolecular interaction potential, we developed a prestretching methodology in our group to form secondary ionic bonding network under stress.37 The universal approach can be expanded to the current system to maximize the interaction between PVA, BSA, and TA molecules. Figure 6a shows the tensile stress of samples with different prestretching ratios followed by TA-mediated physical crosslinking. It is seen that increasing the prestretching strain of PVA/BSA hydrogel drastically affects the mechanical strength of the resultant TA-PVA/BSA hydrogel. When the prestrtching strain is 180%, the tensile stress of the resultant hydrogel can reach ∼9.5 MPa. As schematic drawing in the inset of Figure 6a, prestretching exposes more hydrogen bonding groups to TA molecules and drives close the interacting molecules along direction normal to the prestretching direction. When the complexation interaction occurs more sufficiently, it results in significantly improved mechanical strength. Besides, the asprepared TA-PVA/BSA hydrogel formed under prestretching treatment shows obvious anisotropy. Two rectangular TAPVA/BSA hydrogel strips were cut from a 150% prestretched strain sample, one is along the stretch direction (parallel), the other is perpendicular to the stretch direction (vertical). As

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CONCLUSION In summary, we utilize the noncovalent interactions form tannic acid (TA) with BSA proteins and poly(vinyl alcohol)

Figure 6. (a) Schematic diagram of prestretching and the tensile stress of TA (5%)-PVA/BSA (5 mg/mL) hydrogel at different stretching ratios (100%−180%); (b) tensile stress−strain curves of the two anisotropic TA (5%)-PVA/BSA (5 mg/mL) hydrogel samples cut from orthogonal directions (a, parallel; b, vertical). Sample thickness, 0.8 mm; width, 6 mm). F


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Figure 7. TA (5%)-PVA/BSA (5 mg/mL) hydrogel shows good water-retention ability. (a) Mass retaining percentage of the pure PVA hydrogel cylinder and TA (5%)-PVA/BSA (5 mg/mL) hydrogel cylinder at the different heating time; (b) optical photographs of PVA hydrogel cylinder and TA(5%)-PVA/BSA(5 mg/mL) hydrogel cylinder before/after treating at 50 °C for 22 h; (c) snapshots showing compression process of heated TAPVA/BSA hydrogel cylinder after treating at 50 °C for 22 h.

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ACKNOWLEDGMENTS We gratefully acknowledge support from Ministry of Science and Technology (2016YFC1100401) and the National Natural Science Foundation of China (51573199, 51335010, 21434009).

(PVA) chains to improve mechanical property of the pure PVA hydogel, and construct physically cross-linked multinetwork hydrogel TA-PVA/BSA. The as-prepared TA-PVA/BSA hydrogel demonstrated high mechanical strength, good waterretention ability. Moreover, the mechanical property of hydrogel can be well-regulated by varying the concentration of TA and BSA proteins, soaking time in TA, and the thickness of the hydrogel pieces. The TA-PVA/BSA composite hydrogel can demonstrate ultrahigh but anisotropic mechanical strength by forming the secondary network under prestretching. TAPVA/BSA hydrogel showed an inhomogeneous layered structure by controlling soaking time in TA, resembling human skin, which enables its good water-loss-resistance property. The TA-PVA/BSA composite hydrogel is a pure physical cross-linking network based on the noncovalent interaction mechanism. It can be a candidate for promising biomaterial for widespread application.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.7b04290. Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) patterns, the water content, the crosssectional SEM morphology and compression property of the as-prepared hydrogels (PDF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Feng Zhou: 0000-0001-7136-9233 Author Contributions †

R.X. and S.M. contributed equally. The manuscript was written and discussed through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest. G


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