Self-Activated Healable Hydrogels with Reversible ... - ACS Publications

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Self-Activated Healable Hydrogels with Reversible Temperature Responsiveness Ruixue Chang, Xuemeng Wang, Xu Li, Heng An, and Jianglei Qin* College of Chemistry and Environmental Science, Hebei University, 180 East Wusi Road, Baoding 071002, China S Supporting Information *

ABSTRACT: The self-healable polymer hydrogel along with reversible temperature responsiveness was prepared through self-catalyzed dynamic acylhydrazone formation and exchange without any additional stimulus or catalyst. The hydrogel was prepared from a copolymer of N-isopropylacrylamide and acylhydrazine P(NIPAM-co-AH) cross-linked by PEO dialdehyde. Besides self-healed under catalysis of acid and aniline, the hydrogel can also self-heal activated by excess of acylhydrazine groups. Without interference of catalyst during the hydrogel formation and self-healing, this kind of hydrogel prepared from biocompatible polymers can be used in more areas including biotechnology and be more persistent. The hydrogel with a large part of the PNIPAM segment also showed temperature responsiveness around body temperature influenced by the variation in group ratio. This self-healable hydrogel has great potential application in areas related to bioscience and biotechnology. KEYWORDS: self-healable hydrogel, self-catalysis, dynamic covalent cross-linking, thermoresponsive, sol−gel transition with redox reversibility,5,10 dynamic-covalent boronic esters bond,8,20 oxime bonds,23,31 or other kinds of reversible bonds32−34 are also used to design self-healable polymer materials. Among these self-healable materials, self-healable hydrogel is the most attractive since they play importance role in living creatures and have great potential application in bioscience. But the self-healing processes of most dynamic hydrogels were catalyzed by mild acid, aniline, or other kinds of triggers, which are inapplicable or even toxic to organisms, and the self-healing property would vanish when the catalyst run away. Self-healable hydrogels from biocompatible polymers without any stimulus or catalysis are greatly expected. In this paper, self-healable polymeric hydrogels were prepared based on biocompatible Poly(N-isopropylacrylamide) (PNIPAM) copolymer and PEO, which are widely used to prepare thermoresponsive hydrogel for bioapplications.14,35−38 On the basis of dynamic acylhydrazone cross-linking, the hydrogel showed self-healing property under catalysis and the sol−gel transition responsive to pH. More importantly, this hydrogels also formed under neutral conditions and selfhealability can be activated by excess of acylhydrazine group without any catalyst or triggers. Moreover, the self-healable hydrogels showed temperature responsiveness based on temperature sensitivity of PNIPAM segment. To the best of our knowledge, there is no precedent report on the self-healable

1. INTRODUCTION Self-healing and self-repairing ability is one of the most fascinating ability of living creatures compared to our nonliving counterpart. Accordingly, the living creatures can automatically repair damages on their body by self-healing process; as a result, the damage is repaired and the function of the organ is restored. This striking self-healing feature has inspired researchers to design self-healable synthetic materials and hope to reveal the self-healing mystery of organisms. Thus, the self-healable materials1−6 and gels7−12 draw great attentions and made great progress in past decade.13 Based on the cross-linking point in the materials, the self-healable polymer materials can be defined as self-healable chemical14 and physical materials,6,11,12,15−19 respectively. Besides physical cross-linked ones, self-healable materials based on dynamic chemical bonds show better stability and draw great attentions in past years.4,5,20−25 In 2002, Fred Wudl reported a thermally remendable polymeric material based on reversible nature of Diels−Alder reaction upon heating.26 Chung et al. prepared a crack healable polymeric materials via reversible cycloaddition of cinnamate.2 Deng et al. designed a novel self-healable polymeric gels based on dynamic covalent acylhydrazone bond27,28 and showed pH sol−gel transition under various acidities.29,30 Matyjaszewski reported selfhealable polymer material under UV-triggered reshuffling reaction of trithiocarbonate.25 Imato had reported dynamic materials with diarylbibenzofuranone employed as a dynamic covalent bond through coupling of stable radicals.7,21 Cheng’s group designed a dynamic urea bond as a reversible unit to prepare self-healable polymer materials.5 The disulfide bond © 2016 American Chemical Society

Received: July 8, 2016 Accepted: September 2, 2016 Published: September 2, 2016 25544

DOI: 10.1021/acsami.6b08279 ACS Appl. Mater. Interfaces 2016, 8, 25544−25551

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ACS Applied Materials & Interfaces

Scheme 1. Synthesis of P(NIPAM-co-AH) through Two-Step Reaction and Preparation of Self-Catalyzed Healable Hydrogel Thereof

the transparencies at various temperatures were observed and recorded by a digital camera. 2.2.3. Characterizations. 1H NMR characterizations was carried out on a Bruker 600 MHz spectrometer (Avance III, Bruker Co. Switzerland) at room temperature in CDCl3. A Varian 600 IR spectrometer was used to obtain the Fourier-transform infrared (FTIR) spectra. The samples were dissolved in CH2Cl2 and casted on a KBr plate for characterization. Gel permeation chromatography (GPC) was performed on a set of Shimazu GPC with a refractive index detector and a set of Styragel columns. THF was used as eluent with a flow rate of 1.0 mL min−1 and the characterization was carried out at 30 °C. Scanning electron microscopy (SEM) image was observed on a JSM-7500 microscope to determine the morphology of the micro porous material with operating voltage at 10 kV. The mechanical properties of the hydrogels were characterized on an AR2000ex rheometer with a 25 mm plate at 25 °C. The scanning frequency range was from 0.05 to 100 rad s−1 with the strain of 5%. Modulus (G′, G″) and complex viscosity (η*) were compared to determine the characteristic of the gels and cross-linking mechanism.

chemical hydrogel with thermoresponsiveness based on selfactivation of biocompatible polymer. This kind of self-healable hydrogel with thermoresponsivity without additional catalyst have great potential applications in bioscience and technology including biodiagnosis, artificial organ, drug loading, delivery, etc.

2. MATERIALS AND METHODS 2.1. Materials. N-Isopropylacrylamide (NIPAM), 4-hydroxybenzaldehyde, methyl acrylate (MA), tosyl chloride and Poly(ethylene oxide) (PEO45, Mn = 2000) were purchased from Maya Reagent Co. Dialdehyde-terminated PEO45 (PEO45 dialdehyde) was prepared according to literature.30 S-1-Dodecyl-S′-(R,R′-dimethyl-R″-acetic acid) trithiocarbonate (DDMAT) was synthesized according to previous reports.39 All other reagents and solvents including hydrazine hydrate, methanol, and dioxane were supplied by Kermel Chemical Reagent Co. and used as-received. All water used in experiments is deionized water. 2.2. Method. 2.2.1. Synthesis of P(NIPAM313-co-AH40) through RAFT Copolymerization and Hydrazinolysis. The P(NIPAM-co-MA) was prepared through RAFT copolymerization and hydrazinolysis as shown in Scheme 1. DDMAT (36.4 mg, 0.1 mmol), NIPAM (3.96 g, 35 mmol), MA (0.39 g, 4.5 mmol) and AIBN (4.9 mg, 0.3 mmol) were dissolved in 4.5 mL dioxane in a 25 mL reaction tube. The oxygen was removed by three freeze−pump−thaw cycles and the reaction was carried out for 24 h at 60 °C under continuous stirring.16,40,41 The polymer product was purified by precipitating in cold petroleum ether four times. The molecular weight of the polymer was evaluated by monomer conversion. The composition of the polymer was calculated from 1H NMR spectrum by comparing peak areas corresponding protons. Hydrazinolysis of the PMA segments was carried out in methanol by excess of hydrazine hydrate (80% in water, w/w) at 80 °C for 72 h.30 After the mixture was cooled to room temperature, the methanol was evaporated under reduced pressure and the copolymer precipitated from the solution under heating. The product was dissolved in deionized water again and excess of hydrazine hydrate was removed by dialysis against deionized water, and the solution was then lyophilized to obtain P(NIPAM313-co-AH40). 2.2.2. Preparation and Self-Healing of Hydrogel. Hydrogel were obtained by dissolving the P(NIPAM 313 -co-AH40 ) and PEO 45 dialdehyde in deionized water with or without catalyst. The typical procedure was described as follows: 200 mg of P(NIPAM313-co-AH40) (0.2 mmol of acylhydrazine) and 230 mg of PEO45 dialdehyde (0.2 mmol aldehyde) were dissolved in 3.9 mL of deionized water to form a clear solution with total concentration of 10%. Then 5% glacier acetic acid based on solution weight was added and mixed together. The solution was then put into a sealed mold to form a hydrogel. Rheology test was carried out at 25 °C after the gel was aged for 12 h. Each hydrogel was cut into two pieces across the center, and then the two pieces were put back into the sealed mold with close contact for 24 h. Photos were taken before and after the self-healing processes. To characterize the temperature responsiveness of the hydrogel, we put samples in glass vials into the heating water bath. The temperature was increased gradually and held for 5 min at each temperature, and

3. RESULTS AND DISCUSSION 3.1. Synthesis of P(NIPAM-co-AH) through RAFT Polymerization and Hydrazinolysis. Copolymer of P(NIPAM-co-AH) was prepared through RAFT polymerization and hydrazinolysis. The synthesis of P(NIPAM-co-MA) was initiated by AIBN and mediated by DDMAT (Scheme 1). The GPC curve showed the copolymerization was well-mediated (Figure S1, PDI = 1.21) and the Mn of the copolymer was 38.8 kDa evaluated by monomer conversion. The 1H NMR spectra of the copolymers are shown in Figure 1. By comparing the peak areas of b and c in Figure 1 (bottom), the PMA molar

Figure 1. 1H NMR spectra of P(NIPAM-co-MA) in CDCl3 (bottom) and P(NIPAM-co-AH) in DMSO-d6 (up). The solvents were marked as *. 25545


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ACS Applied Materials & Interfaces ratio was 11.3%. The DP of PNIPAM and PMA were calculated to be 313 and 40, respectively, and the copolymer was named as P(NIPAM313-co-MA40). Hydrazinolysis of the PMA unit was carried out in methanol by hydrazine hydrate according to literature30 and determined by 1H NMR. The PNIPAM segments were pretty stable under hydrazinolysis while the MA segments were transformed into acylhydrazine segments almost completely, as shown in Figure 1 (top). The methyl group almost disappeared (c) and new peak appeared at 9.78 ppm (d). By comparing the area of related peak areas, the hydrazinolysis ratio is calculated to about 90% and the polymer was named as P(NIPAM313-co-AH40) for convenience. The phase transition temperature increased due to higher hydrophilicity of acylhydrazine compared to MA segment. The phase transition temperature of the polymers was determined by turbidity studies using a UV−vis spectrophotometer in 0.5 mg mL−1 solutions at 500 nm wavelength. The change in transmission of the solutions with increasing temperature is shown in Figure 2. The phase transition

Figure 3. FT-IR spectra of copolymer before (top) and after hydrazinolysis (bottom).

copolymer structure during hydrazinolysis, as shown in Figure 3 (bottom). This process also provides an effective method to prepare acylhydrazine-containing copolymers. 3.2. Preparation of Self-Healable Hydrogel and Mechanism Study. The hydrogels were prepared by reaction of P(NIPAM313-co-AH40) and PEO45 dialdehyde. It was noted that PEO45 dialdehyde can cross-link the P(NIPAM313-coAH40) to form dynamic covalent cross-linked hydrogel at 10% weight ratio of gelator concentration, rather than self-healable PNIPAM hydrogels based on physical cross-linking.43,44 The hydrogel prepared from 1:1 ratio of acylhydrazine to aldehyde groups with 5% weight ratio of glacier acetic acid is illustrated in Figure 4-1. It was noted that clear hydrogel formed within 3 min with the apparent pH of ≈3, as shown in Figure 4-1a. Then the hydrogel was cut into two pieces (Figure 4-1b) and put back into the sealed mold with close contact along the cut line. The two pieces merged into a single piece after incubated at room for 24 h (Figure 4-1c) and cannot be split along the cut line under stretching (Figure 4-1d). However, some scars can still be figured out where the hydrogel pieces were not contacted very well, this is because of the poor reshaping rate of the hydrogel based on high functionality of the polymer. When the gel was broken into small pieces and put into a glass vial, the pieces merged into a whole. But this process is pretty slow and cost 2 weeks to finish the reshape process (Figure S2). The aniline also catalyzed the formation of the acylhydrazone bond like reported in literature.44 With 1% weight ratio of aniline addition, the hydrogel also formed within 3 min without acetic acid and the cut hydrogel self-healed after contacted for 24 h, as shown in Figure 4-2a−d. This result is consistent with literature report that the acid as catalyst is not necessary and the aniline can also catalyze the reversible reaction of acylhydrazone.30,45 It is not surprising to see that hydrogel also formed in about 10 min without any catalyst as reported30,46 (Figure 4-3a). When the gelator concentration was increased to 20%, gel formed within 2 min with large amount of bubbles (Figure S3); the gel also formed with 5% gelator concentration, but the strength was too low to carry out self-healing experiment. It was reported that acylhydrazone bond did not form without catalysis in DMF;29 possible reason is that the protons in water or on PNIPAM segment acted as catalyst as well in this research. But because the reversible bonds were mostly locked

Figure 2. Thermoresponsiveness of P(NIPAM313-co-MA40) (square) and P(NIPAM313-co-AH40) (circle). The insert is the photograph of P(NIPAM313-co-AH40) at room temperature and 60 °C separately.

temperature of P(NIPAM313-co-MA40) is 31.4 °C, a little bit lower than pure PNIPAM because of the hydrophobic MA segment. The phase transition temperature of P(NIPAM313-coAH40) increased to 47.1 °C because the hydrophobic MA segments were transformed into hydrophilic acylhydrazine and different pendant groups can influence the LCST of PNIPAM.42 The photographs of the P(NIPAM313-co-AH40) solutions at room temperature and 60 °C are inserted for direct visualization. After the MA segments were transformed into acylhydrazine segments, the Tg of the copolymer increased from 132.4 to 148.1 °C because of increased intermolecular force. The polymerization and hydrazinolysis were also tracked by FT-IR, two absorbance representing carbonyl groups appeared on FT-IR spectrum of P(NIPAM313-co-MA40), as shown in Figure 3 (top). The absorbance at 1730 cm−1 is derived from the ester bond of PMA and the absorbance at 1646 cm−1 is derived from PNIPAM. After hydrazinolysis, the absorbance at 1646 cm−1 kept at its original position; however, the absorbance at 1730 cm−1 disappeared, proved the ester bond was transformed into amide during hydrazinolysis. At the same time, other peaks kept intact, showed high stability of the 25546


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Figure 4. Self-healing properties of hydrogels through additional catalyst and self-activation. (a) As-prepared hydrogel; (b) cut through the center; (c) contacted for 24 h; (d) under stretching; (the 1:1, etc., down the left side represent the group ratio of acylhydrazine to aldehyde; no catalyst was used for 3 or 4).

Scheme 2. Acylhydrazone Exchange Reaction Triggered by Excess of Acylhydrazine Catalyzed by Active Protons

matter of the pH value. To prove this hypothesis, several experiments were carried out for verification. First, 2% N, Ndimethylaniline without active proton on N atom was added into 10% gelator solution with 1:1 group ratio, the hydrogel did not form until 16 h; much slower that that without N, Ndimethylaniline, proved the active protons on aniline is key factor while acted as catalyst. The hydrogel prepared with excess of aldehyde did not self-heal in 24 h either. The organic gel in DMF was also prepared to confirm the catalysis reactivity of PNIPAM, it was noted the gel also formed with gelator content of 10% in 12 h, compared to that no gel formed without catalysis.29 This amazing self-healing process with selfactivation does not need to worry about the toxicity or running away of the catalyst and ensures better persistence in application, which also ensured better biocompatibility and application properties in related areas. Because this catalysis mechanism can be based on amide bond, which is widely existed in organism as proteins and polypeptide, this discovery could help us to understand the mechanism of organisms’ selfrepairing. 3.3. Mechanical Property of Dynamic Hydrogel. Mechanical properties of hydrogels with or without catalyst were characterized by dynamic rheological measurements. In

and the active functional group density is extremely low under neutral conditions, the hydrogel did not self-heal after contacted for 24 h, as shown in Figure 4-3b−d. However, the formation of the hydrogel via active proton catalysis is still of great importance to explain the mechanism of the reaction and have great potential application especially in bioscience and biotechnology. Copolymer with multifunctional groups allows the variation of group ratios. To regulate the density of pendant acylhydrazine groups, hydrogel was prepared with 2:1 ratio of acylhydrazine to aldehyde. It was amazing to see that this hydrogel also self-healed in 24 h, as shown in Figure 4-4a−d. These results indicated that the dynamic reaction of acylhydrazone bond can be accelerated by excess of acylhydrazine. Since the equilibrium of one reaction would not be changed by group density and the reversible reaction of acylhydrazone bond without catalyst need pretty high temperature and long time scale,4 the mechanism for this self-healing process is supposed to through acylhydrazone exchange rather than reversible reaction, as shown in Scheme 2. On the basis of the above mechanism, it is the active protons including that in water, on aniline and PNIPAM segment acted as catalyst through H-bonding like the formation of the hydrogel no 25547


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Figure 5. Rheological properties of hydrogel at 25 °C with 10% solid content and various compositions. (a) 1:1 with 5% glacier acetic acid; (b) 1:1 without catalyst; (c) 2:1 without catalyst; (d) comparison of G′ and η* for above three samples.

Figure 6. Schematic illustration and pH responsiveness of the slef-healable hydrogel with 5% acetic acid. (a) As-prepared hydrogel; (b) after 1 drop of HCl addition; (c) after addition of N(C2H5)3.

Figure 5, the storage moduli (G′), loss moduli (G″) and complex viscosity (η*) of the hydrogels are presented as a function of frequency (ω) at a strain of γ = 5.0%. All three samples (Figure 5a−c) display a solid-like characteristic with G′ > G″ with the frequency as low as ω = 0.08 rad S1−. For 1:1 group ratio of acylhydrazine to aldehyde with 5% glacier acetic acid as catalyst, the G′ decreased and G″ increased a little bit at low frequency, as shown in Figure 5a. It was assumed that the G′ is frequency-independent for chemical gels cross-linked by stable covalent bonds, whereas the gel containing reversible covalent bonds and supramolecular networks are frequencydependent.30 So it is reasonable to see this trend for the selfhealable hydrogel with 5% glacier acetic acid as catalyst. But because of high cross-linking density in the hydrogel, the G′ kept higher than G″ at pretty low frequency.24 For 1:1 ratio without catalyst or self-healing property, the G′ > G″ is illustrated in whole range with G′ independent of frequency, indicated the acylhydrazone bonds are locked at neutral conditions, as shown in Figure 5b. But it is surprised to notice that hydrogel with 2:1 ratio of acylhydrazine to aldehyde with self-healable property (Figure 5c), the rheological curves are identical to that of Figure 5b, indicated the same kind of cross-

linking. However, this hydrogel was self-healable because the acylhydrazone exchange reaction can be activated by excess of acylhydrazine rather than reversible reaction, as shown in Scheme 2. Also this result is consistent with the mechanism in Scheme 2. The G′ and η* of above three samples are compared in Figure 5d. The G′ and η* of the self-healable hydrogel with 1:1 group ratio is lower than that without catalyst, showing the lower cross-linking density because of equilibrium characteristic of acylhydrazone bond under acid. As a result, some acylhydrazine and aldehyde groups are coexisted in the hydrogel, which reduced the cross-linking density of the hydrogel. The self-healable hydrogel with 2:1 group ratio showed the highest G′, but the composition of gelator in the hydrogel was different, cross-linking density cannot be compared by the G′. 3.4. Sol−Gel Transition and Thermoresponsiveness of Self-Healable Hydrogel. Although the cross-linking density is much higher, the hydrogel still show pH reversible responsiveness based on dynamic property of acylhydrazone bond, as shown in Figure 6. When one drop (∼30 mg) of HCl (36.5%) was added into 1 g of the as prepared self-healable 25548


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healable hydrogel can be obtained again and no difference was noticed after repeated for 5 times (Figure S6). This property endows the self-healable hydrogel with improved properties in bioscience and biotechnology such as biodiagnose, controlled drug loading and delivery, etc. The morphology of the self-healable hydrogel was observed by SEM, the photographs of the sample lyophilized from 2:1 group ratio hydrogel are shown in Figure 8 with different magnification. As shown in Figure 8, irregular pores with chemical cross-linked walls are illustrated. The self-healable walls contain large amount of PNIPAM segment and show thermo-responsivity around body temperature. Based on above results, self-healable hydrogel with self-activated self-healing property and temperature responsive property around body temperature was obtained. Without additional stimulus during hydrogel formation and self-healing, this kind of self-healable hydrogel could have better biocompatibility. Moreover, the acylhydrazine is a mild functional group compared to amido group and the acylhydrazone is a bioactive group used in drugs. As a result, these hydrogels could have great potential application in bioscience and biotechnology including biodiagnosis, controlled drug loading, and delivery, which is under intensive study.

hydrogel (Figure 6a), the hydrogel dissolved in several minute and transparent solution was obtained, as shown in Figure 6b. When the HCl was neutralized by addition of N(C2H5)3, hydrogel was reobtained again (Figure 6c). The appearance of the hydrogel was of no difference with that before pH cycle except bubbles generated during shaking. All other hydrogels showed the same pH responsiveness and showed no difference up to 6 cycles. As an important temperature-sensitive polymer, the selfhealable hydrogels with a large PNIPAM content show temperature-responsiveness as well. Furthermore, the phase transition temperature can be regulated by excess of hydrophilic acylhydrazine groups. As shown in Figure 7, the hydrogel with

4. CONCLUSIONS In summary, we prepared catalyst free self-healing hydrogel with reversible temperature responsiveness based on dynamic covalent acylhydrazone from copolymer of P(NIPAM313-coAH40) and PEO45 dialdehyde. Besides traditional catalyst, the hydrogel also formed and self-healed through acylhydrazone exchange activated by excess of acylhydrazine. Based on living radical polymerization, the ratio and molecular weight of the P(NIPAM-co-AH) can be controlled conveniently. The hydrazinolysis result indicated that the NIPAM segments are very stable and the MA segment can be hydrazinolyzed selectively. This process also provides an effective method to prepare acylhydrazine containing polymers. The formation and self-healing process of this kind of hydrogel with self-catalysis have great potential application in bioscience and biotechnology without worrying about the runaway or toxicity of catalyst. Furthermore, this process and mechanism are very similar to those of living creatures and help us to understand the mechanism of organisms′ self-repairing.

Figure 7. Thermoresponsiveness of hydrogels in response to temperature during heating. The left sample is prepared from 2:1 ratio of acylhydrazine and aldehyde; the right sample is 1:1 ratio with 5% acetic acid. The temperatures are (a) 30, (b) 33, (c) 35, (d) 38, (e) 40, and (f) 50 °C.

1:1 ratio of acylhydrazine to aldehyde and 5% glacier acetic acid turned from clear gel into opaque mainly between 35 and 38 °C, lower than LCST of P(NIPAM313-co-AH40) because most of the acylhydrazine group was consumed. With excess of hydrophilic acylhydrazine groups existed, the hydrogel with 2:1 ratio of acylhydrazine to aldehyde become translucent when the temperature increased above 40 °C; but the transmittance decreased slowly with increasing temperature within large temperature range (Figure S4). However, rather than phase separation of physical gel,38 thermoresponsivity of the selfhealable hydrogels are completely reversible even if phase separation occurred at above 60 °C (Figure S5). The self-

Figure 8. SEM images of hydrogels prepared with 2:1 group ratio after lyophilization. (the magnification is (a) 50 and (b) 200 times, respectively). 25549


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(11) Ueki, T.; Usui, R.; Kitazawa, Y.; Lodge, T. P.; Watanabe, M. Thermally Reversible Ion Gels with Photohealing Properties based on Triblock Copolymer Self-Assembly. Macromolecules 2015, 48, 5928− 5933. (12) Phadke, A.; Zhang, C.; Arman, B.; Hsu, C.-C.; Mashelkar, R. A.; Lele, A. K.; Tauber, M. J.; Arya, G.; Varghese, S. Rapid Self-Healing Hydrogels. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 4383−4388. (13) Yang, Y.; Ding, X.; Urban, M. W. Chemical and Physical Aspects of Self-Healing Materials. Prog. Polym. Sci. 2015, 49−50, 34−59. (14) Miao, L.; Hu, J.; Lu, M.; Tu, Y.; Chen, X.; Li, Y.; Lin, S.; Li, F.; Hu, S. Alkynyl-Functionalization of Hydroxypropyl Cellulose and Thermoresponsive Hydrogel Thereof Prepared with P(NIPAAm-coHEMAPCL). Carbohydr. Polym. 2016, 137, 433−440. (15) Zhan, J.; Zhang, M.; Zhou, M.; Liu, B.; Chen, D.; Liu, Y.; Chen, Q.; Qiu, H.; Yin, S. A Multiple-Responsive Self-Healing Supramolecular Polymer Gel Network Based on Multiple Orthogonal Interactions. Macromol. Rapid Commun. 2014, 35, 1424−1429. (16) Ueki, T.; Nakamura, Y.; Usui, R.; Kitazawa, Y.; So, S.; Lodge, T. P.; Watanabe, M. Photoreversible Gelation of a Triblock Copolymer in an Ionic Liquid. Angew. Chem., Int. Ed. 2015, 54, 3018−3022. (17) Cordier, P.; Tournilhac, F.; Soulie-Ziakovic, C.; Leibler, L. SelfHealing and Thermoreversible Rubber from Supramolecular Assembly. Nature 2008, 451, 977−980. (18) Li, G.; Wu, J.; Wang, B.; Yan, S.; Zhang, K.; Ding, J.; Yin, J. SelfHealing Supramolecular Self-Assembled Hydrogels Based on Poly(Lglutamic acid). Biomacromolecules 2015, 16, 3508−3518. (19) Zhang, M.; Xu, D.; Yan, X.; Chen, J.; Dong, S.; Zheng, B.; Huang, F. Self-Healing Supramolecular Gels Formed by Crown Ether Based Host−Guest Interactions. Angew. Chem. 2012, 124, 7117−7121. (20) Cromwell, O. R.; Chung, J.; Guan, Z. Malleable and SelfHealing Covalent Polymer Networks through Tunable Dynamic Boronic Ester Bonds. J. Am. Chem. Soc. 2015, 137, 6492−6495. (21) Imato, K.; Nishihara, M.; Kanehara, T.; Amamoto, Y.; Takahara, A.; Otsuka, H. Self-Healing of Chemical Gels Cross-linked by Diarylbibenzofuranone-based Trigger-Free Dynamic Covalent Bonds at Room Temperature. Angew. Chem., Int. Ed. 2012, 51, 1138−1142. (22) An, S. Y.; Noh, S. M.; Nam, J. H.; Oh, J. K. Dual SulfideDisulfide Crosslinked Networks with Rapid and Room Temperature Self-Healability. Macromol. Rapid Commun. 2015, 36, 1255−1260. (23) Wei, Z.; Yang, J. H.; Zhou, J.; Xu, F.; Zrinyi, M.; Dussault, P. H.; Osada, Y.; Chen, Y. Self-Healing Gels Based on Constitutional Dynamic Chemistry and Their Potential Applications. Chem. Soc. Rev. 2014, 43, 8114−8131. (24) Mukherjee, S.; Hill, M. R.; Sumerlin, B. S. Self-Healing Hydrogels Containing Reversible Oxime Crosslinks. Soft Matter 2015, 11, 6152−6161. (25) Amamoto, Y.; Kamada, J.; Otsuka, H.; Takahara, A.; Matyjaszewski, K. Repeatable Photoinduced Self-Healing of Covalently Cross-linked Polymers Through Reshuffling of Trithiocarbonate Units. Angew. Chem., Int. Ed. 2011, 50, 1660−1663. (26) Chen, X.; Dam, M. A.; Ono, K.; Mal, A.; Shen, H.; Nutt, S. R.; Sheran, K.; Wudl, F. A Thermally Re-Mendable Cross-Linked Polymeric Material. Science 2002, 295, 1698−1702. (27) Kalia, J.; Raines, R. T. Hydrolytic stability of hydrazones and oximes. Angew. Chem., Int. Ed. 2008, 47, 7523−7526. (28) Yu, F.; Cao, X.; Du, J.; Wang, G.; Chen, X. Multifunctional Hydrogel with Good Structure Integrity, Self-healing, and TissueAdhesive Property Formed by Combining Diels-Alder Click Reaction and Acylhydrazone Bond. ACS Appl. Mater. Interfaces 2015, 7, 24023− 24031. (29) Deng, G.; Tang, C.; Li, F.; Jiang, H.; Chen, Y. Covalent Crosslinked Polymer Gels with Reversible Sol-Gel Transition and SelfHealing Properties. Macromolecules 2010, 43, 1191−1194. (30) Deng, G.; Li, F.; Yu, H.; Liu, F.; Liu, C.; Sun, W.; Jiang, H.; Chen, Y. Dynamic Hydrogels with an Environmental Adaptive SelfHealing Ability and Dual Responsive Sol-Gel Transitions. ACS Macro Lett. 2012, 1, 275−279.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.6b08279. GPC curve of P(NIPAM313-co-MA40), reshape process of self-healable hydrogel with 10% concentration and 5% acetic acid, gel prepared with 20% gelator concentration, transmission curve of hydrogel prepared from 2:1 group ratio vs temperature, hydrogel prepared from 2:1 group ratio above 60 °C and room temperature, reversible thermoresponsiveness of hydrogel with 1:1 group ratio and 5% acetic acid (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Fax: +86-0312-5079359. Phone: +86-15733210284. Author Contributions

The manuscript was written 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.

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ACKNOWLEDGMENTS This research was kindly supported by Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (2014-1685); Hebei University (2013272); Postgraduate’s Innovational Fund Project of Hebei Province (S2016018).

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REFERENCES

(1) Ling, J.; Rong, M.; Zhang, M. Photo-Stimulated Self-Healing Polyurethane Containing Dihydroxyl Coumarin Derivatives. Polymer 2012, 53, 2691−2698. (2) Chung, C.; Roh, Y.; Cho, S.; Kim, J. Crack Healing in Polymeric Materials via Photochemical [2 + 2] cycloaddition. Chem. Mater. 2004, 16, 3982−3984. (3) Ghosh, B.; Urban, M. W. Self-Repairing Oxetane-Substituted Chitosan Polyurethane Networks. Science 2009, 323, 1458−1460. (4) Kuhl, N.; Bode, S.; Bose, R. K.; Vitz, J.; Seifert, A.; Hoeppener, S.; Garcia, S. J.; Spange, S.; van der Zwaag, S.; Hager, M. D.; Schubert, U. S. Acylhydrazones as Reversible Covalent Crosslinkers for Self-Healing Polymers. Adv. Funct. Mater. 2015, 25, 3295−3301. (5) Ying, H.; Zhang, Y.; Cheng, J. Dynamic Urea Bond for the Design of Reversible and Self-Healing Polymers. Nat. Commun. 2014, 5, 3218. (6) Hu, L.; Cheng, X.; Zhang, A. A Facile Method to Prepare UV Light-Triggered Self-Healing Polyphosphazenes. J. Mater. Sci. 2015, 50, 2239−2246. (7) Imato, K.; Ohishi, T.; Nishihara, M.; Takahara, A.; Otsuka, H. Network Reorganization of Dynamic Covalent Polymer Gels with Exchangeable Diarylbibenzofuranone at Ambient Temperature. J. Am. Chem. Soc. 2014, 136, 11839−11845. (8) Cash, J. J.; Kubo, T.; Bapat, A. P.; Sumerlin, B. S. RoomTemperature Self-Healing Polymers Based on Dynamic-Covalent Boronic Esters. Macromolecules 2015, 48, 2098−2106. (9) Ma, X.; Usui, R.; Kitazawa, Y.; Kokubo, H.; Watanabe, M. PhotoHealable Ion Gel with Improved Mechanical Properties using a Tetraarm Diblock Copolymer Containing Azobenzene Groups. Polymer 2015, 78, 42−50. (10) Zhang, P.; Deng, F.; Peng, Y.; Chen, H.; Gao, Y.; Li, H. Redoxand pH-Responsive Polymer Gels with Reversible Sol-Gel Transitions and Self-Healing Properties. RSC Adv. 2014, 4, 47361−47367. 25550


Research Article

ACS Applied Materials & Interfaces (31) Zhou, J.; Zhang, W.; Hong, C.; Pan, C. Silica Nanotubes Decorated by pH-Responsive Diblock Copolymers for Controlled Drug Release. ACS Appl. Mater. Interfaces 2015, 7, 3618−3625. (32) Li, H.; Bai, J.; Shi, Z.; Yin, J. Environmental Friendly Polymers Based on Schiff-Base Reaction with Self-Healing, Remolding and Degradable Ability. Polymer 2016, 85, 106−113. (33) Maiti, B.; Ruidas, B.; De, P. Dynamic Covalent Cross-linked Polymer Gels through the Reaction Between Side-chain beta-Keto Ester and Primary Amine Groups. React. Funct. Polym. 2015, 93, 148− 155. (34) Zheng, P.; McCarthy, T. J. A surprise from 1954: Siloxane Equilibration is a Simple, Robust, and Obvious Polymer Self-Healing Mechanism. J. Am. Chem. Soc. 2012, 134, 2024−2027. (35) James, C.; Johnson, A. L.; Jenkins, A. T. A. Antimicrobial Surface Grafted Thermally Responsive PNIPAM-co-ALA Nano-Gels. Chem. Commun. 2011, 47, 12777−12779. (36) Guan, Y.; Zhang, Y. PNIPAM Microgels for Biomedical Applications: From Dispersed Particles to 3D Assemblies. Soft Matter 2011, 7, 6375−6384. (37) Nguyen, H. H.; Payre, B.; Fitremann, J.; Lauth-de Viguerie, N.; Marty, J.-D. Thermoresponsive Properties of PNIPAM-based Hydrogels: Effect of Molecular Architecture and Embedded Gold Nanoparticles. Langmuir 2015, 31, 4761−4768. (38) Ma, C.; Shi, Y.; Pena, D. A.; Peng, L.; Yu, G. Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Rrelease. Angew. Chem., Int. Ed. 2015, 54, 7376− 7380. (39) Lai, J.; Filla, D.; Shea, R. Functional Polymers from Novel Carboxyl-Terminated Trithiocarbonates as Highly Efficient RAFT Agents. Macromolecules 2002, 35, 6754−6756. (40) Peng, B.; Liu, Y.; Shi, Y.; Li, Z.; Chen, Y. Thermo-Responsive Organic-Inorganic Hybrid Vesicles with Tunable Membrane Permeability. Soft Matter 2012, 8, 12002−12008. (41) Shi, Y.; Wang, X.; Graff, R. W.; Phillip, W. A.; Gao, H. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 239−248. (42) Vatankhah-Varnoosfaderani, M.; Hashmi, S.; GhavamiNejad, A.; Stadler, F. Polym. Chem. 2014, 5, 512−523. (43) Gulyuz, U.; Okay, O. Self-Healing Poly(N-isopropylacrylamide) Hydrogels. Eur. Polym. J. 2015, 72, 12−22. (44) Wang, T.; Zheng, S.; Sun, W.; Liu, X.; Fu, S.; Tong, Z. Notch Insensitive and Self-Healing PNIPAm-PAM-clay Nanocomposite Hydrogels. Soft Matter 2014, 10, 3506−3512. (45) Bhat, V. T.; Caniard, A. M.; Luksch, T.; Brenk, R.; Campopiano, D. J.; Greaney, M. F. Nucleophilic Catalysis of Acylhydrazone Equilibration for Protein-Directed Dynamic Covalent Chemistry. Nat. Chem. 2010, 2, 490−497. (46) Wei, Z.; Yang, J.; Liu, Z.; Xu, F.; Zhou, J.; Zrínyi, M.; Osada, Y.; Chen, Y. Novel Biocompatible Polysaccharide-Based Self-Healing Hydrogel. Adv. Funct. Mater. 2015, 25, 1352−1359.

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