Biodegradable Poly(Acrylic Acid-Co-Acrylamide)/ Poly(Vinyl Alcohol) Double Network Hydrogels with Tunable Mechanics and High Self-Healing Performance

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Article Biodegradable Poly(acrylic acid-co-acrylamide)/ Poly(vinyl alcohol) Double Network Hydrogels with Tunable Mechanics and High Self-healing Performance

Zhanxin Jing * , Aixing Xu, Yan-Qiu Liang *, Zhaoxia Zhang, Chuanming Yu, Pengzhi Hong and Yong Li *

College of Chemistry and Environment, Guangdong Ocean University, Zhanjiang 524088, Guangdong, China; [email protected] (A.X.); [email protected] (Z.Z.); [email protected] (C.Y.); [email protected] (P.H.) * Correspondence: [email protected] (Z.J.); [email protected] (Y.-Q.L.); [email protected] (Y.L.); Tel.: +86-759-238-3300 (Z.J. & Y.-Q.L. & Y.L.) Received: 17 April 2019; Accepted: 12 May 2019; Published: 1 June 2019

Abstract: We proposed a novel strategy in the fabrication of biodegradable poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) (P(AAc-co-Am)/PVA) double network (DN) hydrogels with good mechanical and self-healing properties. In the DN hydrogel system, P(AAc-co-Am) polymers form a network through the ionic coordinates between –COO– and Fe3+ and hydrogen bonding between –COOH and –CONH2, while another network is fabricated by the complexation between PVA and borax. The influences of the composition on the rheological behaviors and mechanical properties of the synthesized DN hydrogels were investigated. The rheological measurements revealed that the viscoelasticity and stiffness of the P(AAc-co-Am)/PVA DN hydrogels increase as the acrylamide and Fe3+ concentrations increase. At 0.05 mmol of Fe3+ and 50% of acrylamide, tensile strength and elongation at break of P(AAc-co-Am)/PVA DN hydrogels could reach 329.5 KPa and 12.9 mm/mm, respectively. These properties arise from the dynamic reversible bonds existed in the P(AAc-co-Am)/PVA DN hydrogels. These reversible bonds also give good self-healing properties, and the maximum self-healing efficiency of P(AAc-co-Am)/PVA DN hydrogels is up to 96.4%. The degradation test of synthesized DN hydrogels was also conducted under simulated physiological conditions and the weight loss could reach 74% in the simulated intestinal fluid. According to the results presented here, the synthesized P(AAc-co-Am)/PVA DN hydrogels have a potential application prospect in various biomedical fields.

Keywords: hydrogel; double network; toughness; self-healing; biodegradable

1. Introduction Hydrogels, which can swell and do not dissolve in water, are cross-linked polymer networks containing a large amount of water [1,2]. They are widely studied and have been applied in many fields, such as drug delivery [2,3], gene delivery [4] and tissue engineering scaffolds [5,6] due to their excellent properties, such as intelligent responsiveness, biocompatibility. However, the traditional synthetic hydrogels have generally weak mechanical strength, poor toughness and low recoverability [7]. This is largely due to their single network structure, which results in the intrinsic structure heterogeneity and the lacking effective energy dissipation mechanisms. This would greatly limit the application of hydrogel materials in tissue engineering materials and regenerative medicine that need generally to withstand large forces [8,9]. Many strategies, such as supramolecular hydrogels [10,11], nanocomposite

Polymers 2019, 11, 952; doi:10.3390/polym11060952 www.mdpi.com/journal/polymers Polymers 2019, 11, 952 2 of 18 hydrogels [12–14] and interpenetrating and double networks hydrogels [15,16], have been proposed to synthesize hydrogels with superior mechanical properties. Nakahata et al. [11] synthesized the supramolecular gel with extremely high toughness and elastic deformation behavior by host-guest interaction, revealing that the reversible nature of host-guest interaction gives the hydrogel self-healing property. Liu et al. [12] synthesized polyacrylamide/graphene oxide nanocomposite hydrogels by in situ free radical polymerization, found that graphene oxide nanosheets played a role of cross-linker. And the synthesized nanocomposite hydrogels showed high tensile strength, high toughness, and a large elongation at break. Liu et al. [17] developed a new design strategy to synthesize a dual ionic cross-linked polyethylene glycol (PEG)/poly(acrylamide-co-acrylic acid) (PAMAA) double network hydrogels, and found that the synthesized double network hydrogels can achieve high mechanical properties (stress of ~0.36 MPa and strain of ~1350%). Among these methods, the double-network strategy is considered as the eﬀective route to synthesize high strength and toughness hydrogels. Double network (DN) hydrogels, which show outstanding comprehensive mechanical properties with respect to single network hydrogels, have two interpenetrating polymer networks [18,19]. The unique contrasting network structures and eﬃcient energy dissipation mechanism endow the excellent mechanical properties to hydrogel materials. The introduction of the dynamically reversible network into DN hydrogel not only improves their mechanical properties, but also exhibits rapid self-healing capacity. Recently, many researchers [20–22] have begun to focus on the construction of double network hydrogels with self-healing property. The self-healing property of hydrogels is primary dependent on various dynamically reversible covalent, or non-covalent, such as ionic interactions [23,24] hydrogen bonding [25], hydrophobic interactions [26], host-guest interactions [27], metal-ligand interactions [28], etc. Agar/PAMAAc double network gels were synthesized by introduction of ionic coordination interaction in the second network and it was found that the double network hydrogels show extremely high mechanical properties, fast self-recovery and excellent fatigue resistance properties [29]. A double network hydrogel based on poly(vinyl alcohol) and polyacrylamide was synthesized by polymer-tannic acid multiple hydrogen bonds, found that the synthesized hydrogels have strong toughness, good self-recoverability, rapid self-healing, and versatile adhesiveness [30]. Therefore, hydrogels with excellent mechanical properties and self-healing capacity synthesized by double network technology is an important way to expand their applications. At present, the research on the double network hydrogels with self-healing properties has focused more on this situation: one network is based on covalent bonds, the another network is based on non-covalent or reversible bonds. Double network hydrogels constructed by two reversible networks based on non-covalent bonds or reversible bonds is rarely reported. In this study, we present a simple strategy based on dynamically reversible double cross-linked networks, which can be used for the design and construction of high mechanical performances and self-healing poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) (P(AAc-co-Am)/PVA) double network hydrogels. Borax aqueous solution was employed to dissolve PVA, and poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels were prepared via free radical polymerization in the presence of Fe3+. In the poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogel, borate ion would form the “di-ol” complex with PVA chains to fabricate one network, and Fe3+ would form the ionic coordination interactions with poly(acrylic acid-co-acrylamide) macromolecular chains to form another network.

2. Experimental Section

2.1. Materials and Reagents Acrylic acid (AAc, AR), acrylamide (Am, AR) and borax (AR) were purchased from Shanghai Macklin Biochemical Co., Ltd; Polyvinyl alcohol (PVA, DP = 1750 50) and Ammonium persulfate ± (APS, AR) were provided by the Sinopharm Chemical Reagent Co., Ltd, Shanghai, China; Ferric chloride hexahydrate (FeCl 6H O, AR) was obtained from Guangdong Guanghua Sci-Tech Co., Ltd., 3· 2 Polymers 2019, 11, 952 3 of 18

Shantou, Guangdong, China. All the reagents were used as received without further puriﬁcation. All solutions were prepared using distilled water.

2.2. Synthesis of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels A typical synthesis process of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels was described as follows: Firstly, PVA (0.4 g) was added to 8 mL of H2O containing borax (50 mg), and stirred for 30 min at room temperature to make the swelling of PVA; Secondly, the mixture 3+ was stirred at 95 ◦C for 2 h to ensure the complete dissolution of PVA, and 200 µL of Fe ions aqueous solution (0.50 mmol/mL) was added, and then cooled to 40 ◦C; Next, acrylic acid (1.0 g) and acrylamide (1.0 g) were added to the above solution, and 20 mg of APS was added under vigorous stirring; Subsequently, the aforementioned solution was injected to a specific mold and eliminated the bubble by vacuuming; The bubble-removed mold was placed to a thermostat at 60 ◦C for 6 h, and placed at 20 C for 24 h; Eventually, the prepared sample was taken out of the mold and sealed, and denoted − ◦ as Gel-8. The Fe3+ concentration and the ratio of AAc/Am were adjusted to synthesize poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels with different compositions, as listed in Table1. To meet the needs of the test, di fferent shapes of molds are used to prepare samples with different specifications, such as cylindrical samples with diameters of 8 mm and 12 mm, films with a thickness of about 1~2 mm.

Table 1. P(AAc-co-Am)/PVA double network hydrogels with various compositions.

Am/AAc Fe3+ Water content Samples APS (g) PVA (g) Borax (mg) H O (mL) (g/g) (mmol) 2 (wt %) a Gel-1 1:9 0.05 0.02 0.4 50 8 70.51 0.74 ± Gel-2 3:7 0.05 0.02 0.4 50 8 71.74 0.02 ± Gel-3 5:5 0.05 0.02 0.4 50 8 69.44 0.73 ± Gel-4 7:3 0.05 0.02 0.4 50 8 73.45 0.50 ± Gel-5 9:1 0.05 0.02 0.4 50 8 71.60 0.44 ± Gel-6 5:5 0.01 0.02 0.4 50 8 70.17 0.59 ± Gel-7 5:5 0.025 0.02 0.4 50 8 72.39 0.82 ± Gel-8 5:5 0.10 0.02 0.4 50 8 72.75 0.54 ± Gel-9 5:5 0.20 0.02 0.4 50 8 71.26 0.63 ± Gel-10 5:5 0.30 0.02 0.4 50 8 75.75 0.22 ± wo w a Water content of the hydrogels were calculated by the following equation: water content(%) = − d 100%, wd × where wo and wd are the weight of the hydrogel before and after drying.

2.3. Hydrogel Characterization

2.3.1. FT-IR The samples were dried in a vacuum oven to the constant weight, and ground into powder. Afterwards, a certain amount of sample was mixed with KBr, and then compressed. Eventually, the prepared discs was analyzed by Fourier transform infrared spectroscopy (FT-IR, Nicolet, Madison, WI, USA).

2.3.2. Swelling Ratio The dried hydrogel was immersed in 80 mL of phosphate buﬀer solution (pH = 7.4, I = 0.1) at 37 ◦C. After a certain time interval, the sample was weighted after removing the surface water with a ﬁlter paper. The swelling ratio can be calculated by the following equation:

Wt W swelling ratio (g/g) = − d (1) Wd where Wd is the dry weight of sample, Wt is the wet weight of samples after immersing in phosphate buﬀer solution for the time t. Polymers 2019, 11, 952 4 of 18

2.3.3. Rheological Characterization The rheological properties of the synthesized hydrogels were formed on a MCR302 strain-controlled rheometer (Anton Paar, Graz, Austria) using plate-and plate geometry (diameter 25mm, gap 1000 µm), through three different modes: (a) the dynamic strain sweep from 0.01 to 500% with constant frequency of 10 rad/s was first performed at 37 ◦C, and the storage modulus was recorded to define the linear viscoelastic region in which the storage modulus is independent to the strain amplitude; (b) the viscoelastic parameters, including shear storage modulus, loss modulus, complex viscosity, and loss tangent as functions of angular frequency (ω) were measured over the ω range of 0.1–100 rad/s at strain= 1%, and the measured temperature was controlled at 37 ◦C; (c) the alternate step strain sweep test was performed at a fixed angular frequency (10 rad/s) at 37 ◦C, amplitude oscillatory strains were switched from small strain (γ = 1.0%) to subsequent large strain (γ=100%) with 100 s for every strain interval. The storage modulus, loss modulus dependence of time was recorded.

2.3.4. Tensile Testing Tensile test of all samples was measured using a 500N universal testing machine (Jinan Zhongluchang Testing Machine Manufacturing Co., Ltd, Jinan, Shandong, China) at a uniaxial stretching speed of 50 mm/min at the room temperature. The size of cylindrical sample was 8 mm in diameter and 60 mm in length. Each sample was repeated ﬁve times to ensure repeatability.

2.3.5. Compression Testing Compression experiment was performed on a 10KN universal testing machine (Jinan Zhongluchang Testing Machine Manufacturing Co., Ltd, Jinan, Shandong, China). The cylindrical samples of 12 20 mm2 (diameter height) were placed on the lower plate and compressed by the × × upper plate at a compression speed of 20 mm/min at the room temperature. The tests of all samples were conducted in triplicate.

2.3.6. Self-Healing Property Self-healing property of the prepared hydrogel was evaluated by comparing the tensile fracture behaviors of original and healed samples. The cylindrical samples (8 60 mm2) were first cut in the × center, then the two halves were contacted together and put in a plastic syringe with a diameter of 8 mm. The plunger of the syringe was pressed to ensure full contact with the interface. The healing time was varied from 8 h to 48 h, and the healing temperature was varied from 30 ◦C to 50 ◦C. After self-healing, tensile tests of the healed samples were measured to evaluate the healing efficiency. The healing efficiency (HEstress, HEstrain) can be calculated by the followed equation:

Fh HEstress(%) = 100% (2) Fo ×

Sh HEstrain(%) = 100% (3) So × where Fo and So are the tensile strength and elongation at break of original sample, respectively; Fh and Sh are the tensile strength and elongation at break of the healed samples, respectively. The average values and errors were calculated from at least three independent samples for each specimen.

2.3.7. Degradation Testing Degradation experiments were performed in phosphate buffer solution (pH = 7.4, I = 0.1) and in simulated intestinal fluid with 50 U/mL trypsin (pH = 7.4, I = 0.1). The dried cylindrical hydrogels (about 0.15 g) were first swollen in phosphate buffer solution for 48 h. Then, the swollen hydrogels were placed in 80 mL of degradation fluid and degraded in thermostatic oscillator (30 r/min) at 37 ◦C for 10 days. The degradation ratio was determined by the following equation: Polymers 2019, 11, 952 5 of 18

Wo W weight loss (%) = − 100% (4) Wo × where Wo and W are the dried weight of samples before and after degradation, respectively. The tests of all samples were conducted in triplicate.

3. Results and Discussion

3.1. Formation and Structure Analysis The formation mechanism of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels are displayed in Scheme1. Firstly, PVA was dissolved in the borax aqueous solution at 95 ◦C. During the experiment, we found that the fluidity of the solution was getting worse and the white analogous hydrogel formed as the temperature decreased. This is attributed to the formation of a network structure of PVA and borax, which is a reversible crosslinking reaction. The crosslinking mechanism of borate ion with PVA chains was known to be a “di-ol” complex, which was formed between one borate ion and two di-ol units [31,32]. When the temperature was cooled to 40 ◦C, Fe3+ ions aqueous solution is added. The phenomenon reveals that the incorporation of Fe3+ ions improves the fluidity of the mixture, indicating that the part of crosslinking points of the borate ion with PVA chains is damaged. This also demonstrates that the formed bond of the borate ion with PVA chains is reversible. Next, acrylic acid and acrylamide were added, and the APS aqueous solution was added to initiate the polymerization of AAc and Am monomers. This would form the linear poly(acrylic acid-co-acrylamide) macromolecular chain with pendant carboxyl groups and amide groups. The coordination between Fe3+ ions and carboxyl groups could play a role of cross-linking point, resulting in the formation of ionic cross-linked network based on poly(acrylic acid-co-acrylamide). While the hydrogen bonding force may be also form between the pendant carboxyl group and amide group. Therefore, a double network hydrogel based on PVA and poly(acrylic acid-co-acrylamide) was synthesized. In the double network structure, the first network based PVA and borax and the second network based poly(acrylic acid-co-acrylamide) and Fe3+ ions are dynamically reversible. These structures endow the poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels with excellentPolymers mechanical 2018, 10, x FOR PEER strength REVIEW and self-healing properties. 6 of 19

Scheme 1.SchemeSchematic 1. Schematic diagram diagram of synthesisof synthesis ofof P(AAc P(AAc-co-Am)-co-Am)/PVA/PVA double double network network hydrogels hydrogels..

To further analyze the structure of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels, FT-IR spectra of PVA, poly(acrylic acid-co-acrylamide), poly(acrylic-co- acrylamide)/poly(vinyl alcohol) double network hydrogel were also measured, as displayed in Figure 1. In the spectrum of PVA, the broad peak at about 3420 cm−1 is assigned to –OH and C–OH stretching. The peak at 2925 cm−1 is attributed to asymmetric –CH2- group stretching vibration. The peak at 1417 cm−1 is due to -OH bending vibration of the hydroxyl group. The peaks at 1090 and 810 cm-1 are ascribed to C–O stretching and C–C stretching vibration, respectively [33]. For poly(acrylic acid-co-acrylamide), the peak at 3436 cm−1 is attributed to the -NH stretching vibration of the acrylamide unit, which overlapped with the -OH groups of acrylate units. The peak at 2938 cm−1 are assigned to the C–H absorption band caused by the methyl and methylene groups of poly(acrylic acid-co-acrylamide). It can be observed that the superposition of amide group (1650 cm−1) and C=O in carboxyl group (1720 cm−1) result in the band shift of the C=O stretching vibration (1636 cm-1), suggesting that the strong hydrogen bonds are formed between –COOH and –CONH2 [34,35]. In FT- IR spectrum of sample Gel-9, there presents several characteristic peaks of poly(acrylic acid-co- acrylamide)/poly(vinyl alcohol) double network hydrogels. These peaks at 1423 cm−1, 828 cm−1, 650 cm−1 are ascribed to asymmetric stretching relaxation of B-O-C, B-O stretching from residual B(OH)4, bending of B-O-B linkages within borate networks, respectively [36,37]. This reveals that the polyvinyl alcohol-based dynamically reversible cross-linking network is formed due to the occurrence of complexation between PVA and borate. The reduced absorption peak at 1006 cm-1 is also observed, assigned to the formation of coordination interactions between Fe3+ and –COO- groups in the poly(acrylic acid-co-acrylamide) chains [23]. This indicates that another physically cross-linking network is formed at between Fe3+ and poly(acrylic acid-co-acrylamide). These results demonstrate that poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels are successfully synthesized by dynamically reversible cross-linking network.

Polymers 2019, 11, 952 6 of 18

To further analyze the structure of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels, FT-IR spectra of PVA, poly(acrylic acid-co-acrylamide), poly(acrylic-co- acrylamide)/poly(vinyl alcohol) double network hydrogel were also measured, as displayed in Figure1. 1 In the spectrum of PVA, the broad peak at about 3420 cm− is assigned to –OH and C–OH stretching. The 1 1 peak at 2925 cm− is attributed to asymmetric –CH2- group stretching vibration. The peak at 1417 cm− 1 is due to -OH bending vibration of the hydroxyl group. The peaks at 1090 and 810 cm− are ascribed to C–O stretching and C–C stretching vibration, respectively [33]. For poly(acrylic acid-co-acrylamide), 1 the peak at 3436 cm− is attributed to the -NH stretching vibration of the acrylamide unit, which 1 overlapped with the -OH groups of acrylate units. The peak at 2938 cm− are assigned to the C–H absorption band caused by the methyl and methylene groups of poly(acrylic acid-co-acrylamide). 1 It can be observed that the superposition of amide group (1650 cm− ) and C=O in carboxyl group 1 1 (1720 cm− ) result in the band shift of the C=O stretching vibration (1636 cm− ), suggesting that the strong hydrogen bonds are formed between –COOH and –CONH2 [34,35]. In FT-IR spectrum of sample Gel-9, there presents several characteristic peaks of poly(acrylic acid-co-acrylamide)/poly(vinyl 1 1 1 alcohol) double network hydrogels. These peaks at 1423 cm− , 828 cm− , 650 cm− are ascribed to asymmetric stretching relaxation of B-O-C, B-O stretching from residual B(OH)4, bending of B-O-B linkages within borate networks, respectively [36,37]. This reveals that the polyvinyl alcohol-based dynamically reversible cross-linking network is formed due to the occurrence of complexation 1 between PVA and borate. The reduced absorption peak at 1006 cm− is also observed, assigned 3+ to the formation of coordination interactions between Fe and –COO− groups in the poly(acrylic acid-co-acrylamide) chains [23]. This indicates that another physically cross-linking network is formed at between Fe3+ and poly(acrylic acid-co-acrylamide). These results demonstrate that poly(acrylic acid-Polymersco-acrylamide) 2018, 10, x FOR/ poly(vinylPEER REVIEW alcohol) double network hydrogels are successfully synthesized7 of by 19 dynamically reversible cross-linking network.

PVA

2925 810 1090

1417 Gel-9

3420 830 646 1006 P(AAc-co-Am) 2928 1423

Transmittance (%) Transmittance

3431 1006 2938 1636

3436 4000 3500 3000 2500 2000 1500 1000 500 Wavenumber (cm-1)

Figure 1. Fourier transform infrared spectroscopy (FT-IR) spectra of PVA, P(AAc-co- Am) and P(AAc-Figureco 1.-Am) Fourier/PVA transform double networkinfrared hydrogelspectroscopy (Gel-9). (FT-IR) spectra of PVA, P(AAc-co-Am) and P(AAc- co-Am)/PVA double network hydrogel (Gel-9).

Poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels exhibit excellent mechanical properties that can withstand various deformations, as shown in Figure 2. It can be observed that the cylindrical sample could be easily stretched to 300% of their original length without breaking, and the knotted sample could be stretched (as Figure 2a,b). The cylindrical sample could self-recover to its origin height after removing the applied force, as in Figure 2c. We also found that the hydrogel could recover its original shape without any damage under a sharp blade compression. These phenomena indicate that the synthesized hydrogels possess outstanding toughness and self- recovery properties. Hydrogels are hydrophilic materials composed of water and polymer networks, so their mechanical properties are directly related to water content [31]. One of the important applications of hydrogel materials is tissue engineering. However, for human tissue, its water content is about 70%. Therefore, in this study, the water content of the synthesized P(AAc-co-Am)/PVA double network hydrogels is controlled at ~70% (as listed in Table 1).

Polymers 2019, 11, 952 7 of 18

Poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels exhibit excellent mechanical properties that can withstand various deformations, as shown in Figure2. It can be observed that the cylindrical sample could be easily stretched to 300% of their original length without breaking, and the knotted sample could be stretched (as Figure2a,b). The cylindrical sample could self-recover to its origin height after removing the applied force, as in Figure2c. We also found that the hydrogel could recover its original shape without any damage under a sharp blade compression. These phenomena indicate that the synthesized hydrogels possess outstanding toughness and self-recovery properties. Hydrogels are hydrophilic materials composed of water and polymer networks, so their mechanical properties are directly related to water content [31]. One of the important applications of hydrogel materials is tissue engineering. However, for human tissue, its water content is about 70%. Therefore, in this study, the water content of the synthesized P(AAc-co-Am)/PVA double network hydrogels is Polymers 2018, 10, x FOR PEER REVIEW 8 of 19 controlled at ~70% (as listed in Table1).

FigureFigure 2. 2. PhotographsPhotographs of of P(AAc P(AAc--coco-Am)/PVA-Am)/PVA double double network network h hydrogelsydrogels (Gel (Gel-9)-9) under under different different conditionsconditions demonstrating demonstrating their their excellent excellent mechanical mechanical deformation deformation and and recoverability recoverability.. The The hydrogels hydrogels showingshowing their their ability ability to to withstand withstand stretching stretching (a (a),), knotting knotting (b (b),), compression compression ( (cc,d,d)).. 3.2. Swelling Behavior of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels 3.2. Swelling Behavior of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels Swelling behaviors of the synthesized double network hydrogels were also investigated in Swelling behaviors of the synthesized double network hydrogels were also investigated in phosphate buffer solution (pH = 7.4, I = 0.1) at 37 ◦C, and the swelling ratios as function of time are phosphate buffer solution (pH = 7.4, I = 0.1) at 37 ℃, and the swelling ratios as function of time are shown in Figure3. It is clear that all samples can reach the equilibrium swollen state after immersing shown in Figure 3. It is clear that all samples can reach the equilibrium swollen state after immersing for 72 h, and the swelling ratio is closely related to the hydrogel composition. As in Figure3a, the for 72 h, and the swelling ratio is closely related to the hydrogel composition. As in Figure 3a, the swelling ratio first increases and then decreases with increasing of the content of Am. Swelling swelling ratio first increases and then decreases with increasing of the content of Am. Swelling ratio ratio of hydrogel with 30% of Am reaches the maximum (about 30 g/g). This is because a non-ionic of hydrogel with 30% of Am reaches the maximum (about 30 g/g). This is because a non-ionic hydrophilic groups (–CONH2) is introduced into the gel network, and the -CONH2 has a low ionization hydrophilic groups (–CONH2) is introduced into the gel network, and the -CONH2 has a low degree in a near neutral environment [38]. This would result in a certain resistance of the gel to ionization degree in a near neutral environment [38]. This would result in a certain resistance of the salty in the buffer solution. While an increase in the content of Am causes a decrease in the AAc gel to salty in the buffer solution. While an increase in the content of Am causes a decrease in the AAc content, resulting in a decrease in the electrostatic repulsion caused by –COO− groups [39]. The content, resulting in a decrease in the electrostatic repulsion caused by –COO- groups [39]. The influence of the Fe3+ concentrations on swelling ratios is displayed in Figure3b. With increasing of influence of the Fe3+ concentrations on swelling ratios is displayed in Figure 3b. With increasing of the Fe3+ concentrations, the swelling ratio obviously decreases, and the time required to reach the the Fe3+ concentrations, the swelling ratio obviously decreases, and the time required to reach the swelling equilibrium becomes shorter. This is mainly attributed to the cross-linking of Fe3+. The swelling equilibrium becomes shorter. This is mainly attributed to the cross-linking of Fe3+. The increase Fe3+ concentration leads to the formation of more coordination interactions, which restrain the 3+ increase Fe concentration leads to the formation of more coordination interactions3+ , which restrain swelling capacity of hydrogels. And the coordination interactions between Fe and –COO− groups the swelling capacity of hydrogels. And the coordination interactions between Fe3+ and –COO- groups consume carboxyl anions, which weakens the electrostatic repulsion between the polymer segments. consume carboxyl anions, which weakens the electrostatic repulsion between the polymer segments. This is another reason for the decrease in swelling ratios of PVA/poly(acrylic acid-co-acrylamide) double network hydrogels. A similar result has been reported by in the system of PAAc-Fe3+/CNC hydrogels [16].

Polymers 2019, 11, 952 8 of 18

Polymers 2018, 10, x FOR PEER REVIEW 9 of 19 This is another reason for the decrease in swelling ratios of PVA/poly(acrylic acid-co-acrylamide) double network hydrogels. A similar result has been reported by in the system of PAAc-Fe3+/CNC Polymers(a) 40 2018, 10, x FOR PEER REVIEW (b) 40 9 of 19 hydrogels [16]. Gel-1 Gel-6 Gel-2 35 35 Gel-7 Gel-3 Gel-3 Gel-4 40 40 Gel-8 (a)30 Gel-5 (b)30 Gel-1 Gel-9Gel-6 Gel-2 35 35 Gel-10Gel-7 25 Gel-3 25 Gel-3 Gel-4 Gel-8 30 Gel-5 2030 20 Gel-9 25 Gel-10 1525 15

Swelling ratio (g/g) Swelling ratio Swelling ratio (g/g) Swelling ratio 20 1020 10

15 155 5

Swelling ratio (g/g) Swelling ratio Swelling ratio (g/g) Swelling ratio 10 100 0 0 12 24 36 48 60 72 84 96 0 24 48 72 96 5 5 time (h) time (h) 0 0 0 12 24 36 48 60 72 84 96 0 24 48 72 96 Figure 3. Variation of swellingtime (h) ratio of P(AAc-co-Am)/PVA double networktime hydrogels (h) as function of time at 37 ℃: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with various Fe3+ Figure 3. Variation of swelling ratio of P(AAc-co-Am)/PVA double network hydrogels as function of concentrations. Figure 3. Variation of swelling ratio of P(AAc-co-Am)/PVA double network hydrogels3+ as function of time at 37 ◦C: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with various Fe concentrations. time at 37 ℃: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with various Fe3+ 3.3. Rheological Behaviors of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels 3.3. Rheologicalconcentrations Behaviors. of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels The storage modulus (G’) as function of strain for poly(acrylic acid-co-acrylamide)/poly(vinyl The storage modulus (G0) as function of strain for poly(acrylic acid-co-acrylamide)/poly(vinyl 3.3. Rheological Behaviors of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels alcohol)alcohol) doubledouble networknetwork hydrogelshydrogels areare shownshown inin FigureFigure4 .4. ItIt isis clear clear that that all all samples samples displayed displayed a a typical elastic response [16,18]. The G’ of DN hydrogels are independent of the applied strain when typicalThe elastic storage response modulus [16, 18(G].’) Theas function G0 of DN of hydrogels strain for arepoly(acrylic independent acid of-co the-acrylamide) applied strain/poly( whenvinyl the strain is lower than the certain value (γc), revealing a viscoelastic solid. The G’ values gradually thealcohol strain) double is lower network than the hydrogels certain value are (shownγc), revealing in Figure a viscoelastic 4. It is clear solid. that Theall samples G0 values displayed gradually a decreasedecreasetypical elastic aboveabove response thethe certaincertain [16,18 value.value.]. The ThisThis G’ indicatesindicateof DN hydrogelss thatthat DNDN are hydrogelshydrogels independent undergoesundergoes of the aa applied transitiontransition strain fromfrom when thethe quasi-solid state to a quasi-liquid state. As shown in Figure 4a, with increasing of the Am contents, quasi-solidthe strain is state lower to athan quasi-liquid the certa state.in value As ( shownγc), revealing in Figure a 4viscoelastica, with increasing solid. The of the G’ Am values contents, gradually the the G’ of DN hydrogels increases, while the corresponding γc decreases. This indicated that the Gdecrease0 of DN hydrogelsabove the increases,certain value. while This the indicate correspondings that DNγc decreases.hydrogels Thisundergoes indicated a transition that the increased from the Amincreasedquasi contents-solid Am state improve contents to a quasi the improve sti-liquidﬀness, the state. butstiffness, reduceAs shown but the reduce in ability Fig theure to ability sustain4a, with to largersustain increasing deformation larger of deformationthe Am [31 contents,]. It [ can31]. It can be observed in Figure 4b that the G’ of DN hydrogel increases3 + as the Fe3+ concentrations bethe observed G’ of DN in Figurehydrogels4b that increases, the G 0 of while DN thehydrogel corresponding increases γ asc decreases. the Fe concentrations This indicated increases, that the increases, but the corresponding γc decreases. This reveals that the 3 increased+ Fe3+ concentrations butincreased the corresponding Am contentsγ improvec decreases. the stiffness, This reveals but reduce that the the increased ability to Fe sustainconcentrations larger deformation increase [ the31]. stiincreaseIt ﬀ canness be ofthe observed the stiffness DN hydrogels, in of Figtheure DNleading 4b hydrogels, that to the the leadingG decreasing’ of DN to the hydrogel of decreasing the ability increases toof maintainthe as ability the larger Fe to3+ maintain concentrations deformation. larger deformation. This is attributed to the cross-linking density increased by ionic coordinates3+ 3+ between Thisincreases, is attributed but the to correspondingthe cross-linking γc density decreases. increased This reveals by ionic that coordinates the increased between Fe Fe concentrationsand –COO−. 3+ - ToFeincrease ensure and –the thatCOO stiffness the. To dynamic ensure of the that oscillatoryDN thehydrogels, dynamic deformation leading oscillatory wasto the deformation a lineardecreasing viscoelastic wasof the a linearability region, viscoelastic to a maintain strain (γ region, =larger1%) wasadeformation. strain selected (γ = 1%) in This the was followingis selectedattributed oscillation in tothe the following cross tests.-linking oscillation density tests. increased by ionic coordinates between Fe3+ and –COO-. To ensure that the dynamic oscillatory deformation was a linear viscoelastic region, 5 a strain(a) 10 (5γ = 1%) was selected in the following oscillation(b)10 tests. Gel-1 Gel-2 Gel-3 5 5 (a) 10 Gel-4 (b)10 Gel-5 4 104 Gel-1 10 Gel-2 Gel-3 Gel-4 Gel-5 4 4 G' (Pa) G' (Pa) 10 10

3 3 10 10 Gel-6 Gel-3

G' (Pa) G' (Pa) Gel-8 Gel-9 3 3 10 10 Gel-6 102 102 Gel-3 10-2 10-1 100 101 102 103 10-2 10-1 Gel-8100 101 102 103 Gel-9 Strain (%) Strain (%) 102 102 Figure 4.10-2The strain10-1 amplitude100 sweep101 test102 of P(AAc-103 co-Am)10/PVA-2 double10-1 network100 hydrogels101 10 at2 a ﬁxed103 Figure 4. The strain amplitudeStrain (%) sweep test of P(AAc-co-Am)/PVA double networkStrain (%) hydrogels at a fixed angular frequency (10 rad/s) at 37 ◦C: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with variousangular Fe frequency3+ concentrations. (10 rad/s) at 37 °C: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with various Fe3+ concentrations. Figure 4. The strain amplitude sweep test of P(AAc-co-Am)/PVA double network hydrogels at a fixed angular frequency (10 rad/s) at 37 °C: (a) hydrogels with various Am/AAc ratios; (b) hydrogels with various Fe3+ concentrations.

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To further explain the influence of the composition on the viscoelastic properties of P(AAc-co- To further explain the influence of the composition on the viscoelastic properties of AM)/PVA DN hydrogels, oscillatory measurements were performed at 37 °C , as shown in Figure 5. P(AAc-co-AM)/PVA DN hydrogels, oscillatory measurements were performed at 37 ◦C, as shown It is clear that the storage modulus (G’) is larger than the loss modulus (G’’) under all frequency range, in Figure5. It is clear that the storage modulus (G 0) is larger than the loss modulus (G00) under and the moduli are significantly weak dependent on the frequency. This is a characteristic of a solid- all frequency range, and the moduli are significantly weak dependent on the frequency. This is a like viscoelastic behavior [40,41]. It is well known that the storage modulus can be used to evaluate characteristic of a solid-like viscoelastic behavior [40,41]. It is well known that the storage modulus the extent of gel network formation. The higher storage modulus of the gel, the stronger is gel can be used to evaluate the extent of gel network formation. The higher storage modulus of the intensity [42]. As in Figure 5a, when increasing the Am content, the G’ and G’’ obviously increases. gel, the stronger is gel intensity [42]. As in Figure5a, when increasing the Am content, the G and The possible reason for this is that the increased Am content leads to the formation of hydrogen0 G00 obviously increases. The possible reason for this is that the increased Am content leads to the bonding between –COOH and –CONH2, improving the cross-linking points in the poly(acrylic acid- formation of hydrogen bonding between –COOH and –CONH2, improving the cross-linking points in co-acrylamide) network. It is also observed that Tanδ = G’’/G’ blow 0.40 reveals weak dependency the poly(acrylic acid-co-acrylamide) network. It is also observed that Tanδ = G00/G0 blow 0.40 reveals 3+ on the frequency. Figure 5b shows the G’ and G’’ of hydrogels with different Fe concentration3+ weak dependency on the frequency. Figure5b shows the G 0 and G00 of hydrogels with different Fe as a function of frequency. It can be found that the G’ of hydrogels increases as the Fe33++ concentration as a function of frequency. It can be found that the G0 of hydrogels increases as the Fe concentration increases, while the G’’ first increases and then decreases. Tanδ = G’’/G’ below 0.45 concentration increases, while the G00 first increases and then decreases. Tanδ = G00/G0 below 0.45 showsshows alsoalso weakweak dependency dependency on on the the frequency. frequency. A A similar similar phenomenon phenomenon has has alsoalso beenbeen reportedreported byby HussainHussain etet alal inin thethe hydroxyethylhydroxyethyl cellulosecellulose/P(AA/P(AAc-c-coco-Am)-Fe-Am)-Fe33++ hydrogels [43].

Figure 5. Variation of storage modulus (G0) and loss modulus (G00) as function of frequency for Figure 5. Variation of storage modulus (G’) and loss modulus (G’’) as function of frequency for samples measured at γ = 1%: (a) hydrogels with various AAc/Am ratios; (b) hydrogels with various samples measured at γ = 1%: (a) hydrogels with various AAc/Am ratios; (b) hydrogels with various Fe3+ concentrations. Fe3+ concentrations.

Figure6 shows the G 0 and G00 dependence of time in continuous step strain measurements for Figure 6 shows the G’ and G’’ dependence of time in continuous step strain measurements for DN hydrogels. As Figure6a, when a small-amplitude oscillatory force ( γ = 1%) was applied, the G0 DN hydrogels. As Figure 6a, when a small-amplitude oscillatory force (γ = 1%) was applied, the G’ and G00 of Gel-2 are about 10.0 and 3.5 KPa, respectively. Under the application of a large-amplitude and G’’ of Gel-2 are about 10.0 and 3.5 KPa, respectively. Under the application of a large-amplitude oscillatory force (γ = 100%), the G0 and G00 of Gel-2 decrease to 3.4 KPa and 2.5 KPa, respectively. oscillatory force (γ = 100%), the G’ and G’’ of Gel-2 decrease to 3.4 KPa and 2.5 KPa, respectively. However, the G0 and G00 of Ge-2 could recover the initial values when amplitude oscillatory force is decreasedHowever, oncethe G again’ and toG’’ 1.0%. of Ge It-2 is could clear recover that loss the tangent initial at valuesγ = 1% when and amplitudeγ = 100% are oscillatory about 0.35, force and is 0.80,decrease respectively,d once ag indicatingain to 1.0%. that It is sample clear that Gel-2 loss always tangent presented at γ = 1% a solidand γ nature = 100% when are about the amplitude 0.35, and 0.80, respectively, indicating that sample Gel-2 always presented a solid nature when the amplitude oscillatory alternated between 1% and 100%. It can be found by comparing Figure6a–c that G 0 and oscillatory alternated between 1% and 100%. It can be found by comparing Figure 6a–c that G’ and G00 of P(AAc-co-Am)/PVA DN hydrogels decreases under the same oscillatory force as the content of AmG’’ of increases. P(AAc-co The-Am)/PVA tanδ at γ DN= 100% hydrogels decreases decreases as the under Am content the same increase. oscillatory In Figure force6 d,as itthe is clearcontent that of theAm tan increases.δ of Gel-9 The with tan 0.20δ at γ mmol = 100% Fe3 decreases+ at γ = 1% as andthe Amγ = 100%content are increase. 0.05~0.08 In and Figure 1.5~2.0, 6d, it respectively, is clear that indicatingthe tanδ of that Gel the-9 with sample 0.20 undergoes mmol Fe3+ a at transition γ = 1% and from γ the= 100% original are quasi-solid0.05~0.08 and state 1.5~2.0 to the, respectively, quasi-liquid state.indicating These that results the sample indicate undergoes that the P(AAc- a transitionco-Am) from/PVA the DN original hydrogels quasi show-solid good state toughness to the quasi and- self-recoverliquid state. properties.These results indicate that the P(AAc-co-Am)/PVA DN hydrogels show good toughness and self-recover properties.

PolymersPolymers2019 2018,,11 10,, 952x FOR PEER REVIEW 1011 ofof 1819

(a)105 (b)105

Gel-2 Gel-3

104 104

G'&G''(Pa) G'&G''(Pa) 103 103 G' at γ=1% G' at γ=1% G'' at γ=1% G" at γ=1% G' at γ=100% G' at γ=100% G'' at γ=100% G" at γ=100%

2 10 102 0 100 200 300 400 500 0 100 200 300 400 500 time (s) time (s)

5 (c)105 (d)10 Gel-9 Gel-4

104 104

G'&G''(Pa)

G'&G''(Pa) 103 103 G' at γ=1% G' at γ=1% G'' at γ=1% G'' at γ=1% G' at γ=100% G' at γ=100% G'' at γ=100% G'' at γ=100%

102 102 0 100 200 300 400 500 0 100 200 300 400 500 time (s) time (s) Figure 6. Alternate step strain test with small strain to subsequent large strain with 100 s for every Figure 6. Alternate step strain test with small strain to subsequent large strain with 100 s for every strain interval at ﬁxed angular frequency (10 rad/s) at 37 ◦C: (a) Gel-2; (b) Gel-3; (c) Gel-4; (d) Gel-9 strain interval at fixed angular frequency (10 rad/s) at 37 ℃: (a) Gel-2; (b) Gel-3; (c) Gel-4; (d) Gel-9 3.4. Mechanical Properties of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels 3.4. Mechanical Properties of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Mechanical properties of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network Hydrogels hydrogels were investigated by tensile and compression tests. The obtained curves are displayed in FigureMechanical7, and tensile properties strength, of elongation poly(acrylic at break acid and-co-acrylamide) compressive/poly( strengthvinyl obtained alcohol) from double Figure network7 are listedhydrogels in Table were2. Figureinvestigated7a displays by tensile the typical and compression tensile stress-strain tests. The curves obtained of hydrogels curves are with displayed various in AmFigure/AAc 7, ratios.and tensile For sample strength, Gel-1 elongation with 10% at of break Am content, and compressive the tensile strength andobtained elongation from Figure at break 7 areare 24.9 listed KPa in and Table 19.5 2. mm Figure/mm, 7a respectively. displays the By typical increasing tensile the stress Am- contents,strain curves tensile of strengthhydrogels of with DN hydrogelsvarious Am/AAc ﬁrst increases ratios. For and sample then decreases, Gel-1 with while 10% theof Am elongation content, atthe break tensile is alwaysstrength decreasing. and elongation The tensileat break strength are 24.9 of KPa P(AAc- andco 19.-Am)5 mm/mm,/PVA DN respectively. hydrogel with By 50%increasing of Am the content Am contents, is maximum tensile (329.5 strength KPa), andof DN its elongation hydrogels at first break increases is 12.9 andmm /mm. then Bydecreases, increasing while the Amthe elongationcontent, the at network break is based always on 3+ poly(AAc-decreasingco. -Am)-Fe The tensileincreases strength the of hydrogenP(AAc-co- bondingAm)/PVA between DN hydrogel –COOH with and –CONH 50% of 2 Amat the content certain is Femaximum3+ concentrations, (329.5 KPa), resulting and its in elongation the increase at break of reversible is 12.9 mm/mm. cross-linking By increasing points, which the Am would content, enhance the thenetwork mechanical based propertieson poly(AAc of- DNco-Am) hydrogels.-Fe3+ increases By further the hydrogen increasing bonding the Am between contents, – theCOOH hydrogen and – 3+ bondingCONH2 at dominates the certain the Fe poly(AAc-3+ concentrations,co-Am)-Fe resulting. The in hydrogen the increase bonding of reversible is weak cross with-linking respect points, to the 3+ 3+ ionicwhich coordinates would enhance between the -COO mechanical− and Fe properties. An increase of DN in hydrogels. the content By of further Am could increasing lead to thethe FeAm surplus,contents, resulting the hydrogen in that bonding the ionic dominates coordinates the existed poly(AAc between-co-Am) Fe-3Fe+ 3+and. The –COO- hydrogen group bonding are more is likelyweak aswith bidentate respect coordinatesto the ionic coordinates and/or even between monodentate -COO- coordinatesand Fe3+. An [ 44increase]. The typicalin the content compressive of Am stress-straincould lead to of the hydrogels Fe3+ surplus, with resulting various Amin that/AAc the ratios ionic arecoordinates displayed existed in Figure between7c. By Fe increasing3+ and –COO the- Amgroup content, are more the likely compressive as bidentate strength coordinates increases. and/or For P(AAc- even monodentateco-Am)/PVA coordinates DN hydrogels [44]. with The 50%typical of Am,compressive its compressive stress-strain strength of hydrogels at strain 90%with could various reach Am/AAc 5.7 MPa. ratios This are is consistentdisplayed within Fig theure results 7c. By ofincreas rheology.ing the Am content, the compressive strength increases. For P(AAc-co-Am)/PVA DN

Polymers 2018, 10, x FOR PEER REVIEW 12 of 19

hydrogels with 50% of Am, its compressive strength at strain 90% could reach 5.7 MPa. This is Polymersconsistent2019, 11 with, 952 the results of rheology. 11 of 18

(a) 400 (b)400 Gel-6 Gel-1 Gel-7 Gel-2 Gel-3 Gel-3 300 300 Gel-8 Gel-4 Gel-9 Gel-5 Gel-10

200 200

Stress(KPa) Stress (KPa) Stress

100 100

0 0 0 5 10 15 20 0 5 10 15 20 Strain(mm/mm) Strain (mm/mm)

6 12 (c) Gel-1 (d) Gel-6 Gel-2 Gel-7 Gel-3 Gel-3 Gel-4 Gel-8 Gel-5 Gel-9 9 6 Gel-10 12 4

9 4 6 6

2 Stress (MPa) Stress Stress (KPa) Stress 2 3

0 3 0 70 75 80 85 90 70 75 80 85 90

0 0

0 20 40 60 80 0 20 40 60 80 Strain (%) Strain (%) Figure 7. Tensile stress-strain curves (a,b) and compressive stress-strain curves (c,d) of P(AAc-co-Am)/ Figure 7. Tensile stress-strain curves (a,b) and compressive stress-strain curves (c,d) of P(AAc-co- PVA double network hydrogels: (a,c) hydrogels with various Am/AAc ratios; (b,d) hydrogels with Am)/PVA double network hydrogels: (a,c) hydrogels with various Am/AAc ratios; (b,d) hydrogels various Fe3+ concentrations. with various Fe3+ concentrations. Table 2. Mechanical properties of P(AAc-co-Am)/PVA double network hydrogels. Table 2. Mechanical properties of P(AAc-co-Am)/PVA double network hydrogels. Original Healed b Samples Tensile ElongationOriginal at Compressive Tensile HealedElongationb at Strength (KPa) Break (mm/mm) Strength a (MPa) Strength (KPa) Break (mm/mm) SampleGel-1 Tensile24.9 2.3 Elongation 19.5 1.3 at Compressive 1.0 0.2 24.0Tensile6.3 Elongation 13.6 2.0 at ± ± ± ± ± Gel-2 152.5 16.6 14.7 3.4 2.8 0.3a 108.3 22.5 6.2 1.8 s strength± break± strength± strength± break± Gel-3 329.5 30.6 12.9 2.8 4.9 0.5 189.8 10.4 5.4 1.3 ± ± ± ± ± Gel-4 255.0 21.8 10.8 0.8 5.1 0.4 127 16.9 2.71 0.3 ± ± ± ± ± Gel-5 213.5(KPa)16.4 (mm/mm) 8.8 1.0 5.7(MPa)0.6 83.2(KPa)15.6 2.21(mm/mm)0.3 ± ± ± ± ± Gel-6 196.5 25.5 7.6 1.3 4.6 0.4 55.9 9.1 2.2 0.2 ± ± ± ± ± Gel-7Gel-1 24.9224.2 ± 19.82.3 19.5 9.9 ±0.4 1.3 1.0 4.8 ±0.6 0.2 116.124.0 22.9± 6.3 2.913.60.8 ± 2.0 ± ± ± ± ± Gel-8 246.8 22.8 11.6 0.9 7.0 0.7 154.8 5.2 3.3 0.2 ± ± ± ± ± Gel-9 210.0 27.9 10.3 1.1 11.4 1.0 153.4 11.2 3.53 0.6 Gel-2 152.5 ± 16.6 14.7± ± 3.4 2.8 ± 0.3 108.3± ± 22.5 6.2± ± 1.8 Gel-10 64.9 6.0 4.9 0.5 6.8 0.8 54.4 7.2 1.2 0.2 ± ± ± ± ± a b Gel-3 329.5Compressive ± 30.6 strength12.9 at 90% ± 2.8 strain; self-healing4.9 ± 0.5 condition at189.8 40 ◦C ± for 10.4 24h. 5.4 ± 1.3

Gel-4 255.0 ± 21.8 10.8 ± 0.8 5.1 ± 0.4 127 ± 16.9 2.71 ± 0.3 The typical tensile stress-strain curves of P(AAc-co-Am)/PVA DN hydrogels with various Fe3+ concentrationsGel-5 are displayed213.5 ± 16.4 in Figure8.87b. ± It 1.0 can be observed5.7 ± 0.6 that the tensile83.2 ± strength 15.6 and2.21 elongation ± 0.3 at break ﬁrst increase and then decrease as the Fe3+ concentrations increase, and P(AAc-co-Am)/PVA DN hydrogelGel with-6 0.05196.5 mmol ± Fe25.53+ presents7.6 the± 1.3 most tensile4.6 strength. ± 0.4 For DN55.9 hydrogels± 9.1 with2.2 lower± 0.2 Fe3+ concentrations, the dynamic reversible coordination bonds allow the material to break and re-form during stretching. This is because the ionic coordinates between Fe3+ and –COO groups is mainly − in the form triple-dentate coordinates; when the Fe3+ concentration exceeds the certain value, the Polymers 2019, 11, 952 12 of 18

triple-dentate coordinates in the DN hydrogels decreases. The ionic coordinates between –COO− and Fe3+ are more likely as bidentate coordinates and/or even monodentate coordinates, which could decrease in the lower cross-linking density of DN hydrogels. The high Fe3+ concentration could occur the negative effect for the free radical copolymerization reaction of AAc and Am monomers, which is because Fe3+ may consume active free radicals [17,45]. The typical compressive stress-strain curves of hydrogels with various Fe3+ concentrations are shown in Figure7d. It is observed that the compressive strength of DN hydrogels first increases and then decreases as the Fe3+ concentrations increase, which shows similar trend with tensile test of DN hydrogel with various Fe3+ concentrations. The compressive strength of P(AAc-co-Am)/PVA DN hydrogel with 0.20mmol Fe3+ is the maximum and could reach 11.4 MPa at strain 90%. The hysteresis behavior and self-recovery properties of P(AAc-co-Am)/PVA DN hydrogels were also evaluated, as displayed in Figure S1. It is clear that the loading-unloading curves of P(AAc-co-Am)/PVA DN hydrogels (Gel-8) under various strains show obvious hysteresis loops, revealing that the synthesized DN hydrogels could dissipate a large amount of energy in cyclic test. The area of loop increases as the strain increases, showing a higher energy dissipation. This may be attributed to the non-covalent interaction and reversible covalent. A similar result has been reported by Shao et al. [16] in the physically cross-linked PAA-CNF-Fe3+ hydrogels. It can be also observed from Figure S1b that the stress-strain curves gradually recover to the original loading pathway as the resting time increases, especially for the lower strain (<300%). This reveals that self-recovery properties of P(AAc-co-Am)/PVA DN hydrogels show time-dependence. This is assigned to the reorganizing of the reformed bonds. In this process, the ionic coordinates, “di-ol” complex and hydrogen bond act as sacrificial bonds, which endows P(AAc-co-Am)/PVA DN hydrogels with good toughness and self-recovery.

3.5. Self-Healing Properties and Self-Healing Mechanism of Poly(acrylic acid-co-acrylamide)/Poly(vinyl alcohol) Double Network Hydrogels During the experiment, we found that the prepared poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels not only present highly stretchable and resilient properties, but also show the certain self-healing capacity. As shown in Figure8a, a cylindrical sample was cut into two sections. When the freshly fractured surfaces contact, two sections can merge to form a single, cylindrical sample. The self-healed samples can undergo signiﬁcant deformation, as displayed in Figure8b. These phenomena revealed that the synthesized P(AAc- co-Am)/PVA double network hydrogels presents good self-healing performance, which is mainly assigned to the special chemical structures. As shown in Figure8c, the self-healing capacity of P(AAc- co-Am)/PVA double network hydrogels are mainly due to complexation reaction between borate ion and two di-ol units in PVA chains, electrostatic interaction between carboxyl anion and Fe3+ and hydrogen bonding between carboxyl and amide groups, which are dynamically reversible bonds [46–49]. When samples were cut in half, these bonds were damaged. However, the halves were in contact, the carboxyl anion and Fe3+ could produce electrostatic interaction, accelerating the integration of two halves. Simultaneously, complexation reaction between borate ion and two di-ol units in PVA chains and hydrogen bonding between carboxyl and amide in the inter-interface formed again. These reversible bonds together maintain and improve the self-healing capacity of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels. Polymers 2018, 10, x FOR PEER REVIEW 14 of 19 carboxyl and amide groups, which are dynamically reversible bonds [46–49]. When samples were cut in half, these bonds were damaged. However, the halves were in contact, the carboxyl anion and Fe3+ could produce electrostatic interaction, accelerating the integration of two halves. Simultaneously, complexation reaction between borate ion and two di-ol units in PVA chains and hydrogen bonding between carboxyl and amide in the inter-interface formed again. These reversible bonds together maintain and improve the self-healing capacity of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) Polymers 2019, 11, 952 13 of 18 double network hydrogels.

Figure 8. (a,b) presenting the macroscopic self-healing behavior of P(AAc-co-Am)/PVA double Figure 8. (a) and (b) presenting the macroscopic self-healing behavior of P(AAc-co-Am)/PVA double network hydrogels (Gel-9); (c) Schematic of the self-healing mechanism of P(AAc-co-Am)/PVA double network hydrogels (Gel-9); (c) Schematic of the self-healing mechanism of P(AAc-co-Am)/PVA double network hydrogels. network hydrogels. The self-healing conditions of poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogelsThe self were-healing further conditions discussed of and poly(acrylic analyzed, acid and-co the-acrylamide) results were/poly( displayedvinyl alcohol in Figure) double9a,b) networkAs Figure hydrogels9a, the tensile were strengthfurther discussed and elongation and analyzed, at break and of sample the results healed were at 30displayed◦C are in 100.8 Figure KPa 9anda,b) 4.2As Fig mmure/mm, 9a, respectively.the tensile strength By increasing and elongation the self-healing at break temperature, of sample healed the tensile at 30 °C strength are 100.8 and KPaelongation and 4.2 at mm/mm, break obviously respectively. increases. By increasing The influence the self of self-healing-healing temperature, time on the the self-healing tensile strength capacity andwas elongation shown in Figureat break9b. obviously The tensile increases. strength The and influence elongation of self at break-healing increase time on as the self-healingself-healing capacitytime increases, was shown and in the Fig tensileure 9b. strength The tensile and elongationstrength and at breakelongation at 48 at h couldbreak reachincrease 281.0 as the KPa self and- healing10.0 mm time/mm, increases, respectively. and the Yuan tensile et strength al [24] also and reportedelongation that at break the increase at 48 h could time andreach temperature 281.0 KPa andcontributed 10.0 mm/mm, to the respectively. improvement Yuan of self-healinget al [24] also ability, reported which that maythe increase be attributed time and to thetemperature enhanced comobilityntributed of to the the polymer improvement chains atof longerself-healing times ability, and higher which temperatures. may be attributed To deeply to the analyze enhanced the mobilityself-healing of the properties polymer ofchains P(AAc- at longerco-Am) times/PVA and double higher network temperatures. hydrogels, To the deeply self-healing analyze ethefficiency self- healingwas calculated properties by of the P(AAc ratio- ofco the-Am)/PVA tensile strengthdouble network of the self-healing hydrogels, sample the self to-healing the tensile efficiency strength was of calculatedthe original by sample. the ratio It of can the be tensile known strength that the of sample the self Gel-3-healing at 40 sample◦C for 48to hthe could tensile recover strength to 85.3% of the of the original tensile strength. There results reveal that the self-healing properties of the synthesized DN hydrogels improve as the self-healing temperature and time increase. Therefore, the DN hydrogels exhibit excellent self-healing ability. Furthermore, the effect of the compositions on the self-healing property was discussed at a temperature 40 ◦C for 24 h. Tensile strength and elongation at break of healed samples are listed in Table2, and the obtained healing e fficiency is shown in Figure9c,d. As in Figure9c the HEstress and HEstrain of DN hydrogel with 10% of Am content are 96.4% and 69.7%, respectively. By increasing the Am contents, the self-healing efficiency rapidly decreases. For DN Polymers 2018, 10, x FOR PEER REVIEW 15 of 19

original sample. It can be known that the sample Gel-3 at 40 °C for 48 h could recover to 85.3% of the original tensile strength. There results reveal that the self-healing properties of the synthesized DN hydrogels improve as the self-healing temperature and time increase. Therefore, the DN hydrogels exhibit excellent self-healing ability. Furthermore, the effect of the compositions on the self-healing property was discussed at a temperature 40 °C for 24 h. Tensile strength and elongation at break of healed samples are listed in Table 2, and the obtained healing efficiency is shown in Figure 9c,d. As Polymers 2019, 11, 952 14 of 18 in Figure 9c the HEstress and HEstrain of DN hydrogel with 10% of Am content are 96.4% and 69.7%, respectively. By increasing the Am contents, the self-healing efficiency rapidly decreases. For DN hydrogel with 90% of Am content, its HEstress and HEstrain are only 39.0% and 25.1%, respectively. hydrogel with 90% of Am content, its HEstress and HEstrain are only 39.0% and 25.1%, respectively. 3+ FigureFigure9 9dd shows shows the the inﬂuence influence of of the the Fe Fe3+ concentrationsconcentrations on on self self-healing-healing efficiency. eﬃciency. It is clear that the HEstress increases from 28.4% to 83.8% as the Fe3+3+ concentration increases from 0.01 mmol to 0.30 mmol. HEstress increases from 28.4% to 83.8% as the Fe concentration increases from 0.01 mmol to 0.30 mmol.

(a)250 (b)400

30℃ 8h 200 16h 40℃ 300 50℃ 24h 36h 150 48h

200

100 Stres (KPa) Stres

Stress (KPa) Stress

100 50

0 0 0 2 4 6 8 10 0 2 4 6 8 10 12 Strain (mm/mm) Strain (mm/mm)

HEstress HEstress

80 HEstrain 80 HEstrain

60 60

40 40

Healing efficiency (%) efficiency Healing Healing efficiency (%) efficiency Healing 20 20

0 0 Gel-1 Gel-2 Gel-3 Gel-4 Gel-5 Gel-6 Gel-7 Gel-3 Gel-8 Gel-9 Gel-10

Figure 9. Tensile stress-strain curves (a,b) of healed sample Gel-3: (a) various self-healing temperatures; (b) various self-healing times; Healing efficiency (c,d): (c) hydrogels with different Am/AAc ratios; (Figured) hydrogels 9. Tensile with di stressfferent-strain Fe3+ concentrations. curves (a,b) of healed sample Gel-3: (a) various self-healing temperatures; (b) various self-healing times; Healing efficiency (c,d): (c) hydrogels with different 3.6. BiodegradationAm/AAc ratios; Properties (d) hydrogels of Poly(acrylic with different acid-co-acrylamide) Fe3+ concentrations/Poly(vinyl. alcohol) Double Network Hydrogels 3.6. BiodTheegradation biodegradability Properties of hydrogelsof Poly(acrylic has acid an important-co-acrylamide) influences/Poly(vinyl on applications alcohol) Double in biomedicine Network and tissueHydrogels engineering. Therefore, the degradation properties of P(AAc-co-Am)/PVA DN hydrogels were also investigated,The biodegradability and the obtained of hydrogels results has are an displayed important in influences Figure 10. on As applications in Figure 10, thein biomedicine weight loss inand phosphate tissue engi buneering.ffer solution Therefore, (pH = 7.4,the Idegradation= 0.1) is significantly properties less of thanP(AAc that-co of-Am)/PVA the simulated DN hydrogels intestinal fluid.were also The investigated, simulated intestinal and the obtained fluid contains results trypsinare displayed compared in Fig toure the 10. phosphate As in Figure bu 1ff0er, the solution, weight suggestingloss in phosphate that trypsin buffer promotes solution the (pH degradation = 7.4, I = 0.1) of P(AAc- is significantlyco-Am)/PVA less DN than hydrogels. that of the However, simulated the mechanismintestinal fluid. of the The influence simulated oftrypsin intestinal on thefluid degradability contains trypsin of P(AAc- comparedco-Am) to/ PVA) the phosphate double network buffer hydrogelssolution, suggesting is still unclear, that andtrypsin it needs promotes further the research. degradation Figure of 10P(AAca shows-co-Am)/PVA the weight DN loss hydrogels after the. degradation of P(AAc-co-Am)/PVA DN hydrogels with various Am/AAc ratios. It is clear that the weight loss of Gel-1 and Gel-2 is less than 3%, which may be related to the high AAc content. Sun et al [50] reported the analogical result that the PAAc hydrogel is difficult to degrade by buffer solution and enzymes. By increasing the Am content, the weight loss significantly increases. For DN hydrogel with 90% of Am content, the weight loss in phosphate buffer solution and simulated intestinal fluid could reach 70% and 74%, respectively. Figure 10b displayed the influences of Fe3+ concentrations on degradation properties of P(AAc-co-Am)/PVA) DN hydrogels. By increasing the Fe3+ concentrations, Polymers 2018, 10, x FOR PEER REVIEW 16 of 19

However, the mechanism of the influence of trypsin on the degradability of P(AAc-co-Am)/PVA) double network hydrogels is still unclear, and it needs further research. Figure 10a shows the weight loss after the degradation of P(AAc-co-Am)/PVA DN hydrogels with various Am/AAc ratios. It is clear that the weight loss of Gel-1 and Gel-2 is less than 3%, which may be related to the high AAc content. Sun et al [50] reported the analogical result that the PAAc hydrogel is difficult to degrade by buffer solution and enzymes. By increasing the Am content, the weight loss significantly increases. For DN hydrogel with 90% of Am content, the weight loss in phosphate buffer solution and simulated Polymers 2019, 11, 952 15 of 18 intestinal fluid could reach 70% and 74%, respectively. Figure 10b displayed the influences of Fe3+ concentrations on degradation properties of P(AAc-co-Am)/PVA) DN hydrogels. By increasing the theFe3+ weight concentrations, loss is enhanced. the weight For P(AAc-loss is enhancco-Am)e/PVA)d. For DN P(AAc hydrogels-co-Am)/PVA with 0.30) DN mmol hydrogels Fe3+, the with weight 0.30 lossmmol in phosphateFe3+, the weight buffer loss solution in phosphate and simulated buffer intestinalsolution and fluid simulated are 66% and intestinal 71%, respectively. fluid are 66% It canand be71%, also respectively. found from It Figure can be 10 alsob that found the weight from Fig lossure of 1 the0b that sample the withweight lower loss Fe of3+ theconcentrations sample with inlower the simulatedFe3+ concentrations intestinal influid the is simulated much larger intestinal than that fluid of phosphateis much larger buff er than solution, that of and phosphate the difference buffer decreasessolution, and as the the Fedifference3+ concentration decreases increases. as the Fe3+ Thisconcentration is because increases. the network This basedis because on poly(acrylicthe network acid-basedco -acrylamide)on poly(acrylic and acid Fe3-+conot-acrylamide) only exists and the ionicFe3+ not coordination only exists between the ionic –COO– coordination and Fe3 between+, but has – 3+ theCOO hydrogen– and Fe bonding, but has between the hydrogen –COOH bonding and –CONH between2. The –COOH hydrogen and bond –CONH is weak2. The with hydrogen respect ionicbond coordination.is weak with Thisrespect result ionic reveals coordination. that trypsin This at result the simulated reveals that intestinal trypsin fluid at the has simulated different abilityintestinal to degradefluid has ionic different coordination ability to and degrade hydrogen ionic bond. coordination and hydrogen bond.

(a)100 (b)100 in pH=7.4 buffer solution in pH=7.4 buffer solution in simulated intestinal fluid in simulated intestinal fluid 80 80

60 60

40 40 Weight loss (%) loss Weight (%) loss Weight

20 20

0 0 Gel-1 Gel-2 Gel-3 Gel-4 Gel-5 Gel-6 Gel-7 Gel-3 Gel-8 Gel-9 Gel-10

Figure 10. The weight loss of P(AAc-co-Am)/PVAdouble network hydrogels after 10 days of degradation inFigure phosphate 10. The buﬀ weighter solution loss (pH of =P(AAc7.4, I-=co-0.1)Am)/PVA and the double simulated network intestinal hydrogels ﬂuid: (a )after hydrogels 10 days with of 3+ variousdegradation Am/AAc in phosphate ratios; (b) hydrogelsbuffer solution with various(pH = 7.4 Fe, I concentrations.= 0.1) and the simulated intestinal fluid: (a) 3+ 4. Conclusionshydrogels with various Am/AAc ratios; (b) hydrogels with various Fe concentrations.

4. ConclusionsWe synthesized a novel biodegradable poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) double network hydrogels with good mechanical properties and efficient self-healing properties on the basis We synthesized a novel biodegradable poly(acrylic acid-co-acrylamide)/poly(vinyl alcohol) of dynamically reversible bonds. The properties of P(AAc-co-Am)/PVA double network hydrogels, double network hydrogels with good mechanical properties and efficient self-healing properties on such as swelling ratios, mechanical properties, self-healing properties and degradability, are adjusted the basis of dynamically reversible bonds. The properties of P(AAc-co-Am)/PVA double network by tuning the composition. The incorporation of reversible cross-linking network could provide hydrogels, such as swelling ratios, mechanical properties, self-healing properties and degradability, the P(AAc-co-Am)/PVA double network hydrogels with high extensibility, and self-recovery ability. are adjusted by tuning the composition. The incorporation of reversible cross-linking network could P(AAc-co-Am)/PVA double network hydrogels show the tensile strength of 329.5 KPa and elongation provide the P(AAc-co-Am)/PVA double network hydrogels with high extensibility, and self-recovery at break of 12.9 mm/mm, respectively. The compressive strength could reach 11.4 MPa at strain ability. P(AAc-co-Am)/PVA double network hydrogels show the tensile strength of 329.5 KPa and 90%. What is more, the incorporation of dynamically reversible bonds endow the hydrogel with the elongation at break of 12.9 mm/mm, respectively. The compressive strength could reach 11.4 MPa at excellent self-healing properties and degradability, and the self-healing efficiency and weight loss of strain 90%. What is more, the incorporation of dynamically reversible bonds endow the hydrogel P(AAc-co-Am)/PVA double network hydrogels could also reach 96.4% and 74%, respectively. Therefore, with the excellent self-healing properties and degradability, and the self-healing efficiency and the P(AAc-co-Am)/PVA double network hydrogels would have a great potential application in various weight loss of P(AAc-co-Am)/PVA double network hydrogels could also reach 96.4% and 74%, biomedical fields. respectively. Therefore, the P(AAc-co-Am)/PVA double network hydrogels would have a great Supplementarypotential application Materials: in variousThe following biomedical are available fields. online at http://www.mdpi.com/2073-4360/11/6/952/s1. Figure S1: Hysteresis and self-recovery properties of P(AAc-co-AM)/PVA DN hydrogels at room temperature: (a)Supplementary cyclic tensile loading-unloadingMaterials: The following curves are under available different online strains at www.mdpi.com/xxx/s1. at certain resting time (5 min) between two successive measurements; (b) cyclic tensile loading-unloading curves under different strains at certain resting time (30 min) between two successive measurements. Author Contributions: Investigation, Z.J. and A.X.; Data Curation, Z.J. and A.X.; Formal Analysis, Z.Z.; Writing-Original Draft Preparation, Z.J.; Writing-Review & Editing, Z.J. and Y.-Q.L.; Supervision, C.Y.; Project Administration, Y.L. and P.H. Funding: This research was funded by the Natural Science Foundation of Guangdong Province (2018A03037020), Project of enhancing school with innovation of Guangdong ocean university (2017KQNCX089), Science and Technology Planning Project of Zhanjiang City (2017A02016) and Scientific Research Start-Up Funds of Guangdong Ocean University (to Zhanxin Jing). Polymers 2019, 11, 952 16 of 18

Conﬂicts of Interest: The authors declare no conﬂict of interest.

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