Self-Activated Healable Hydrogels with Reversible Temperature

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Self-activated Healable Hydrogels with Reversible Temperature Responsiveness Ruixue Chang, Xuemeng Wang, Xu Li, Heng An, and Jianglei Qin ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b08279 • Publication Date (Web): 02 Sep 2016 Downloaded from http://pubs.acs.org on September 3, 2016

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ACS Applied Materials & Interfaces

Self-activated Healable Hydrogels with Reversible Temperature Responsiveness Ruixue Chang, Xuemeng Wang, Xu Li, Heng An, Jianglei Qin* College of Chemistry and Environmental Science, Hebei University, 180 East Wusi Road, Baoding 071002, China. E-mail: [email protected] KEYWORDS: self-healable hydrogel; self catalysis; dynamic covalent cross-linking; thermoresponsive; sol-gel transition 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-isopropyl acrylamide and acylhydrazine P(NIPAM-co-AH) cross-linked by PEO di-aldehyde. Besides self-healed under catalysis of acid and aniline, the hydrogel can also selfheal activated by excess of acylhydrazine groups. Without interference of catalyst during the hydrogel formation and self-healing, this kind of hydrogel prepared from bio-compatible polymers can be used in more areas including biotechnology and be more persistent. The hydrogel with large part of PNIPAM segment also showed temperature responsiveness around body temperature influenced by variation of group ratio. This self-healable hydrogel has great potential application in areas related to bioscience and biotechnology.

ACS Paragon Plus Environment

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1. Introduction Self-healing and self-repairing ability is one of the most fascinating ability of living creatures compared to our non-living 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 selfhealable polymer materials can be defined as self-healable chemical 14 and physical materials6, 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 re-mendable 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, acidities.

29, 30

28

and showed pH sol-gel transition under various

Matyjaszewski reported self-healable 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 group designed dynamic urea bond as reversible unit to prepare self-healable polymer materials.5 The disulfide bond with redox reversibility,5, 10 dynamic-covalent boronic esters bond,8, 20 oxime bonds23, 31 or other kinds of reversible bonds32-34 are also used to design of 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 bio-compatible polymers without any stimulus or catalysis are greatly expected.


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In this paper, self-healable polymeric hydrogels were prepared based on bio-compatible Poly(N-isopropylacrylamide) (PNIPAM) copolymer and PEO, which are widely used to prepare thermo-responsive hydrogel for bio-applications.14, 35-38 Based on dynamic acylhydrazone crosslinking, 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 self-healability 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 chemical hydrogel with thermo-responsiveness based on selfactivation of bio-compatible polymer. This kind of self-healable hydrogel with thermoresponsivity without additional catalyst have great potential application in bioscience and technology including bio-diagnosis, artificial organ, drug loading and delivery, etc. DDMAT O +

HN

O

O

AIBN

HN

n O O

O

m O

O N H

N

C H

PEO

N C N H H

H2N NH2 o

80 C

O C H

HN

PEO

n m O O HN NH2 O C H

Scheme 1. Synthesis of P(NIPAM-co-AH) through two step reaction and preparation of self-catalyzed healable hydrogel thereof.

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. Di-aldehyde-terminated PEO45 (PEO45 di-aldehyde) was prepared according to literature.30 S-1-Dodecyl-S’-(R,R’-dimethyl-R”-acetic acid) trithiocarbonate (DDMAT) was synthesized according to previous report.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


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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 oC 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 oC 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, then the solution was lyophilized to obtain P(NIPAM313-co-AH40). 2.2.2. Preparation and self-healing of hydrogel. Hydrogel were obtained by dissolving the P(NIPAM313-co-AH40) and PEO45 di-aldehyde 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 di-aldehyde (0.2 mmol aldehyde) were dissolved in 3.9 mL 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. Then the solution was put into a sealed mould to form hydrogel. Rheology test was carried out at 25 oC 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 mould with close contact for 24 h. Photos were taken before and after the self-healing processes. To characterize the temperature responsiveness of the hydrogel, samples in glass vial were put into the heating water bath. The temperature was increased gradually and hold for 5 minute at each temperature, transparency at various temperatures were observed and recorded by a digital camera.


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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 (FT-IR) 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 oC. 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.

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 ratio was 11.3%. The DP of PNIPAM and PMA were calculated to be 313 and 40 separately and the copolymer was named as P(NIPAM313-coMA40).


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*

*

a HN b

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*

n m O O HN d NH2

b a

d

O

a HN

8

m O

b

c

b a 10

O

6

c

4

2

0

Chemical shift (ppm)

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 *.

Hydrazinolysis of the PMA unit was carried out in methanol by hydrazine hydrate according to literature 30 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 temperature of P(NIPAM313-co-MA40) is 31.4 oC, a little bit lower than pure PNIPAM because of the hydrophobic MA segment. The phase transition temperature of P(NIPAM313-co-AH40) increased to 47.1 oC 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 oC are inserted for direct visualization. After the MA segments were transformed into acylhydrazine segments, the Tg of the copolymer increased from 132.4 oC to 148.1 oC because of increased intermolecular force.


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100

75

Transmittance (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


50

25

0 30

40

50

60

70

o

Temperature ( C)

Figure 2. Thermo-responsiveness 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 oC separately. (Credit from Hebei University)

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 copolymer structure during hydrazinolysis, as shown in Figure 3 (bottom). This process also provides an effective method to prepare acylhydrazine containing copolymers.


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P(NIPAM313-co-MA40)

1730

P(NIPAM313-co-AH40)

3298 2972 1646

4000

3200

2400

1600

800

-1

Wavenumber (cm )

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

3.2 Preparation of self-healable hydrogel and mechanism study. The hydrogels were prepared by reaction of P(NIPAM313-co-AH40) and PEO45 di-aldehyde. It was noted that PEO45 di-aldehyde can cross-link the P(NIPAM313-co-AH40) to form dynamic covalent cross-linked hydrogel at 10% weight ratio of gelator concentration, rather than selfhealable 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 minute 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 mould 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 two 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 minute without acetic acid and the cut hydrogel self-healed after contacted for 24 h, as shown in Figure


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4-2(a-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 reported 30, 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 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 4-3(b-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 4-4(a-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. Based on 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 matter of the pH value. To prove this hypothesis, several experiments were carried out for verification. First, 2% N, N-dimethylaniline 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, N-dimethylaniline, 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 hours, compared to that no gel formed without catalysis.29 This amazing self-healing process with self-activation does not need


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to worry about the toxicity or running away of the catalyst and ensures better persistence in application, which also ensured better bio-compatibility and application properties in related areas. Since 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’ self-repairing.

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. represented the group ratio of acylhydrazine to aldehyde; no catalyst was used for 3 and 4). (Credit from Hebei University) O O C

H N

H H2N NH O

O

O H N

N H

O

O

H2N

O

C N H H HN NH

N H

CH

O

N NH

Scheme 2. The acylhydrazone exchange reaction triggered by excess of acylhydrazine catalyzed by active protons.

3.3 Mechanical property of dynamic hydrogel.


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Mechanical properties of hydrogels with or without catalyst were characterized by dynamic rheological measurements. In Figure 5, the storage moduli (G′), loss moduli (G″) and complex viscosity (η*) of the hydrogels are presented as function of frequency (ω) at a strain of γ = 5.0%. All three samples (Figure 5a,b,c) display a solid-like characteristic with G′>G″ with the frequency as low as ω=0.08 rad S-1. 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 5(a). It was assumed that the G′ is frequency-independent for chemical gels cross-linked by stable covalent bonds, while the gel containing reversible covalent bonds and supramolecular networks are frequency-dependent.30 So it is reasonable to see this trend for the self-healable 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 5(b). 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 5 (b), 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.


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b)

a)

10000

10000

1000 G' G'' η∗

100

1000

η ∗/Pa.s

1000 η ∗/Pa.s

G', G"/Pa

G' G'' η∗

G', G"/Pa

1000

100 100

100

10 0.1

1

-1

10

10 0.1

100

1

ω/ rad s

ω/ rad s d)

c)

-1

10

1:1 without catalyst 1:1 5% CH3CO2H

10000 1600

100

10000

2:1 without catalyst 1000 1200

100

G'/Pa

100

800

η ∗/Pa.s

1000

1000 η ∗/Pa.s

G' G'' η∗

G', G"/Pa

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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10

10 100 0.1

1

ω/ rad s

-1

10

100

0.1

1

-1

10

100

ω/ rad s

Figure 5. Rheological properties of hydrogel at 25 oC 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.

The G′ and η* of above three samples are compared in Figure 5(d). The G′ and η* of the selfhealable 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 thermo responsiveness 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 hydrogel (Figure 6a), the hydrogel dissolved in several minute and transparent solution was obtained, as shown in Figure 6 (b). When the HCl was neutralized by addition of N(C2H5)3, hydrogel was reobtained again (Figure 6 c). The appearance of the hydrogel was of no difference with that before


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pH cycle except bubbles generated during shaking. All other hydrogels showed the same pH responsiveness and showed no difference up to 6 cycles.

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. (Credit from Hebei University)

As an important temperature sensitive polymer, the self-healable hydrogels with large part of 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 1:1 ratio of acylhydrazine to aldehyde and 5% glacier acetic acid turned from clear gel into opaque mainly between 35-38 oC, 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 oC; but the transmittance decreased slowly with increasing temperature within large temperature range (Figure S4). However, rather than phase separation of physical gel,38 thermo responsivity of the self-healable hydrogels are completely reversible even if phase separation occurred at above 60 oC (Figure S5). The selfhealable 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 bio-diagnose, 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


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with self-activated self-healing property and temperature responsive property around body temperature was obtained. Without additional stimulus during hydrogel formation and selfhealing, this kind of self-healable hydrogel could have better bio-compatibility. Moreover, the acylhydrazine is a mild functional group compared to amido group and the acylhydrazone is a bio-active group used in drugs. As a result, these hydrogels could have great potential application in bioscience and biotechnology including bio-diagnosis, controlled drug loading and delivery, which is under intensive study.

Figure 7. Thermo-responsiveness 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 temperature for samples a to f are: 30 oC; 33 oC; 35 oC; 38 oC; 40 oC; 50 oC separately. Credit from Hebei University)

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

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-co-


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AH40) and PEO45 di-aldehyde. Besides traditional catalyst, the hydrogel also formed and selfhealed 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 is much similar to that of living creatures and help us to understand the mechanism of organisms′ self-repairing. ASSOCIATED CONTENT Supporting Information. GPC curve of P(NIPAM313-co-MA40), reshape process of selfhealable 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 oC and room temperature, reversible thermo responsiveness of hydrogel with 1:1 group ratio and 5% acetic acid . These materials are available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *Fax: +86-0312-5079359. Phone: +86-15733210284. E-mail: [email protected]. 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. ACKNOWLEDGMENT


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TOC Graphic


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Self-Activated Healable Hydrogels with Reversible Temperature

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