Conductive hydrogel and its preparation method and application

Abstract

The present invention relates to the field of hydrogel technology, and specifically to a conductive hydrogel, a preparation method thereof, and an application thereof. Hyaluronic acid that is formyl- and phenylboronic acid-grafted, a carboxymethyl chitosan solution, and dopamine-modified graphene oxide are uniformly mixed and immediately gelled to obtain the conductive hydrogel. The hydrogel of the present invention is connected through multiple networks, has strong mechanical properties and self-healing properties, and can recover after injury. It can be used as a hydrogel strain sensor and can adhere to the skin surface by itself. The hydrogel has a specific response to pH and redox responsiveness. The hydrogel has a fast gelling speed and high biocompatibility, and can be used in a variety of application scenarios and various complex wound repairs.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogels, and in particular to a conductive hydrogel and a preparation method and application thereof. Background Art

[0002] Flexible sensors have multifunctional application prospects in the fields of wearable devices, soft robots, electronic skin, etc. However, traditional substrates (polymer films and polymer elastomers) have problems such as mismatched mechanical properties, short fatigue life, low strain conduction sensitivity, electrochemical reaction and poor biocompatibility, which limit their application. Therefore, there is an urgent need to develop wearable conductive materials with flexibility, biocompatibility and bioadaptability. Hydrogel is a polymer material with a three-dimensional network structure and a high water content. Due to its excellent physical and chemical properties, good tissue similarity and biocompatibility, and adjustable biological functions, it has attracted widespread attention from researchers.

[0003] Currently, the preparation of conductive hydrogels mainly involves filling conductive components (such as nanometals, carbon materials, metals, ionic liquids or conductive polymers) into the hydrogel network. Although hydrogels have many excellent properties, they are extremely easy to be damaged or even fall off in actual applications. Therefore, in order to achieve long-term physiological signal detection, hydrogels must have adhesion and self-healing properties to extend their service life. More importantly, hydrogels should have multifunctional and intelligent properties, such as antibacterial, antioxidant and multi-responsive properties, to meet practical applications in complex scenarios.

[0004] To date, designing multifunctional conductive hydrogels with excellent biocompatibility remains a significant challenge, and current hydrogel research has mostly focused on one specific aspect. To address this issue, the present invention proposes a novel method for preparing conductive gels, designing a multifunctional and biocompatible hydrogel and its preparation method, which can be used in fields such as skin dressings and flexible sensors. The hydrogel prepared by this method exhibits excellent biocompatibility, self-healing properties, antibacterial properties, photothermal effects, and pH responsiveness, and is promising as a new material for flexible electronic devices. Summary of the Invention

[0005] The present invention provides a preparation method and application of a conductive hydrogel, the purpose of which is to improve the mechanical properties and conductive properties of a natural polysaccharide polymer base.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The first object of the present invention is to provide a method for preparing a conductive hydrogel, comprising the following steps:

[0008] S1: adding the aldehyde-modified and phenylboronic acid-grafted hyaluronic acid to a phosphate buffer solution to obtain solution A;

[0009] S2: adding carboxymethyl chitosan solution and dopamine-modified graphene oxide to phosphate buffer to obtain solution B;

[0010] S3: Mix solution A and solution B evenly and form gel immediately to obtain the conductive hydrogel.

[0011] Preferably, in step S1, the mass fraction of solution A is 10%-20%;

[0012] In step S2, the mass fraction of the carboxymethyl chitosan solution is 10%-15%, and the concentration of the dopamine-modified graphene oxide is 1 mg / mL-3 mg / mL;

[0013] In step S3, the ratio of solution A to solution B is 1:1-1:2.

[0014] Preferably, in step S1, the formaldehyde- and phenylboronic acid-grafted hyaluronic acid is prepared by the following steps:

[0015] S1-1: Add an oxidant to an aqueous solution of hyaluronic acid, allow to react in the dark for 2±1 hours, then add a terminator to terminate the reaction, dialyze, and dry to obtain aldehyde-modified hyaluronic acid;

[0016] S1-2: Dissolve the aldehyde-modified hyaluronic acid in buffer A, add DMTMM and react for 30±10 min, then add 3-aminophenylboronic acid and react for 24±10 h, dialyze, and freeze-dry to obtain aldehyde-modified and phenylboronic acid-grafted hyaluronic acid.

[0017] Preferably, in step S1-1, the oxidant is sodium periodate, and the terminator is ethylene glycol;

[0018] The mass ratio of hyaluronic acid to oxidant is 1:(0.5~1).

[0019] Preferably, in step S1-2, the buffer A is MES buffer;

[0020] The mass ratio of aldehyde-modified hyaluronic acid to DMTMM is 1:(0.5~1);

[0021] The mass ratio of aldehyde-modified hyaluronic acid to 3-aminophenylboronic acid is 1:(0.04~0.1).

[0022] Preferably, in step S2, the dopamine-modified graphene oxide is prepared by the following steps: dissolving graphene oxide in buffer B, then adding dopamine, reacting under nitrogen for 24 hours, centrifuging to obtain a precipitate, washing, and drying to obtain dopamine-modified graphene oxide rGO@PDA.

[0023] Preferably, the buffer B is 100 mM Tris-HCl (pH=8.0); and the washing is performed multiple times with ethanol and water.

[0024] Preferably, in step S2, carboxymethyl chitosan is dissolved in DTP solution at a concentration of (0.1-1) g / mL;

[0025] The DTP solution is prepared by dissolving 3,3'-dithiobis(propionylhydrazide) in a phosphate buffer solution. The concentration of the DTP solution is 2.5 mg / mL-10 mg / mL.

[0026] Another object of the present invention is to provide a conductive hydrogel prepared by the above method.

[0027] Another object of the present invention is to provide an application of the conductive hydrogel in a flexible sensor.

[0028] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0029] 1. The method of the present invention has strong self-healing performance and rapid gelation speed, as well as good biocompatibility.

[0030] 2. The hydrogel of the present invention is connected by multiple networks, such as phenylboronic acid ester bonds, amide bonds, acylhydrazone bonds and other dynamic covalent bonds, so that the hydrogel has strong mechanical properties and self-healing properties, and can recover after damage.

[0031] 3. The hydrogel of the present invention is an adhesive conductive hydrogel material, which can be used as a hydrogel strain sensor and can adhere to the skin surface by itself.

[0032] 4. The hydrogel of the present invention has a specific response to pH. In addition, the hydrogel also has redox responsiveness and can be used in a variety of application scenarios and various complex wound repairs.

[0033] 5. The hydrogel of the present invention has a fast gelling speed and high biocompatibility, and has a strong application development prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is the Fourier infrared image of the hydrogel.

[0035] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the hydrogel.

[0036] Figure 3 This is a test diagram of hydrogel compression strength.

[0037] Figure 4 This is a diagram showing the adhesion effect of hydrogel.

[0038] Figure 5 is a graph of hydrogel adhesion strength.

[0039] Figure 6 This is the hydrogel rheological test diagram.

[0040] Figure 7 is a macroscopic self-healing test diagram of the hydrogel, where: Figure 7A This is the macro self-healing test diagram of Example 1. Figure 7B This is a macroscopic self-healing test diagram of Example 4.

[0041] Figure 8 is the pH sensitivity diagram of the hydrogel.

[0042] Figure 9 is a graph showing the antioxidant properties of the hydrogel.

[0043] Figure 10 is the macroscopic conductive property of the hydrogel.

[0044] Figure 11 is the conductivity diagram of the hydrogel.

[0045] Figure 12 is the hydrogel heating diagram.

[0046] Figure 13 This is a picture of hydrogel photothermal antibacterial effect.

[0047] Figure 14 This is a hydrogel CCK8 test image.

[0048] Figure 15 This is a photograph of live-dead staining of hydrogel. DETAILED DESCRIPTION

[0049] The present invention will be further described below in conjunction with specific embodiments:

[0050] Example 1

[0051] Preparation method of OHA-PBA: 1g hyaluronic acid HA is dissolved in deionized water, 0.535g sodium periodate is added, and the mixture is reacted in the dark for 2h, followed by adding 1.5mL ethylene glycol solution to terminate the reaction for 1h, followed by dialyzation for 3 days, and the resulting solution is freeze-dried to obtain OHA, followed by dissolving 1g OHA in MES buffer, adding 0.7g DMTMM and reacting for half an hour, followed by adding 0.0456g 3-aminophenylboronic acid and reacting for 24h, dialyzing the resulting reaction solution for 3 days, and then freeze-drying the resulting solution to obtain OHA-PBA.

[0052] OHA-PBA was dissolved in PBS buffer (pH = 7.4) to prepare a 10% wt solution.

[0053] Carboxymethyl chitosan was dissolved in PBS buffer to prepare a 10% wt solution.

[0054] 1 mL of OHA-PBA solution was added to 2 mL of carboxymethyl chitosan solution and immediately homogenized to obtain a self-healing hydrogel, in which OHA-PBA:CMC=1:2.

[0055] Example 2

[0056] Preparation method of OHA-PBA: 1g hyaluronic acid HA is dissolved in deionized water, 0.535g sodium periodate is added, and the reaction is carried out in the dark for 2h, followed by adding 1.5mL ethylene glycol solution to terminate the reaction for 1h, followed by dialyzation for 3 days, and the resulting solution is freeze-dried to obtain OHA, followed by dissolving 1g OHA in MES buffer, adding 0.7g DMTMM and reacting for half an hour, followed by adding 0.0456g 3-aminophenylboronic acid and reacting for 24h, dialyzing the resulting reaction solution for 3 days, and then freeze-drying the resulting solution to obtain OHA-PBA.

[0057] Preparation method of rGO@PDA: Graphene oxide (GO) was dissolved in 100mM Tris-HCl (pH=8.0) buffer, and then dopamine (PDA) was added. The reaction was carried out under nitrogen for 24 hours. The reaction solution was centrifuged to obtain a precipitate. The precipitate was then washed with ethanol and water multiple times, and freeze-dried to obtain rGO@PDA.

[0058] OHA-PBA was dissolved in PBS buffer (pH = 7.4) to prepare a 10% wt solution.

[0059] Dissolve 2.5 mg of 3,3'-dithiobis(propionylhydrazide) in 1 mL of PBS buffer to obtain a 2.5 mg / mL DTP solution.

[0060] Subsequently, 0.2 g of carboxymethyl chitosan was dissolved in 2 mL of DTP solution (pH = 7.4) to prepare a CMC / DTP mixed solution with CMC:DTP = 40:1.

[0061] 2 mg of rGO@PDA was dissolved in 2 mL of CMC / DTP mixed solution, ultrasonicated for half an hour, and mixed thoroughly to obtain a mixed solution of rGO@PDA / CMC / DTP.

[0062] 1 mL of the above-mentioned OHA-PBA solution was added to 2 mL of rGO@PDA / CMC / DTP solution and mixed evenly to obtain a self-healing conductive hydrogel immediately, wherein OHA-PBA:CMC:rGO@PDA:DTP = 100:200:2:5.

[0063] Example 3

[0064] Preparation method of OHA-PBA: 1g hyaluronic acid HA is dissolved in deionized water, 0.535g sodium periodate is added, and the mixture is reacted in the dark for 2h, followed by addition of 1.5mL ethylene glycol solution to terminate the reaction for 1h, followed by dialyzation for 3 days, and the resulting solution is freeze-dried to obtain OHA, followed by dissolution of 1g OHA in MES buffer, addition of 0.7g DMTMM for half an hour, and then addition of 0.0456g 3-aminophenylboronic acid for 24h, followed by dialyzation for 3 days, and then freeze-drying the resulting solution to obtain OHA-PBA.

[0065] Preparation method of rGO@PDA: GO was dissolved in 100mM Tris-HCl (pH=8.0) buffer, and then dopamine was added. The reaction was carried out under nitrogen for 24 hours. The reaction solution was centrifuged to obtain a precipitate. The precipitate was then washed with ethanol and water multiple times and freeze-dried to obtain rGO@PDA.

[0066] OHA-PBA was dissolved in PBS buffer (pH = 7.4) to prepare a 10% wt solution.

[0067] Dissolve 2.5 mg of 3,3'-dithiobis(propionylhydrazide) in 1 mL of PBS buffer to obtain a 2.5 mg / mL DTP solution.

[0068] Subsequently, 0.2 g of carboxymethyl chitosan was dissolved in 2 mL of DTP solution (pH = 7.4) to prepare a CMC / DTP mixed solution with CMC:DTP = 40:1.

[0069] 4 mg of rGO@PDA was dissolved in 2 mL of CMC / DTP mixed solution, ultrasonicated for half an hour, and mixed thoroughly to obtain a mixed solution of rGO@PDA / CMC / DTP.

[0070] 1 mL of the above-mentioned OHA-PBA solution was added to 2 mL of rGO@PDA / CMC / DTP solution and mixed evenly to obtain a self-healing conductive hydrogel immediately, wherein OHA-PBA:CMC:rGO@PDA:DTP =100:200:4:5.

[0071] Example 4

[0072] Preparation method of OHA-PBA: 1g hyaluronic acid HA is dissolved in deionized water, 0.535g sodium periodate is added, and the mixture is reacted in the dark for 2h, followed by addition of 1.5mL ethylene glycol solution to terminate the reaction for 1h, followed by dialyzation for 3 days, and the resulting solution is freeze-dried to obtain OHA, followed by dissolution of 1g OHA in MES buffer, addition of 0.7g DMTMM for half an hour, and then addition of 0.0456g 3-aminophenylboronic acid for 24h, followed by dialyzation for 3 days, and then freeze-drying the resulting solution to obtain OHA-PBA.

[0073] The preparation method of rGO@PDA is described. GO is dissolved in 100mM Tris-HCl (pH=8.0) buffer, and then dopamine is added. The reaction is carried out under nitrogen for 24 hours. The reaction solution is centrifuged to obtain a precipitate. The precipitate is then washed with ethanol and water multiple times and freeze-dried to obtain rGO@PDA.

[0074] OHA-PBA was dissolved in PBS buffer (pH = 7.4) to prepare a 10% wt solution.

[0075] Dissolve 2.5 mg of 3,3'-dithiobis(propionylhydrazide) in 1 mL of PBS buffer to obtain a 2.5 mg / mL DTP solution.

[0076] Subsequently, 0.2 g of carboxymethyl chitosan was dissolved in 2 mL of DTP solution (pH = 7.4) to prepare a CMC / DTP mixed solution with CMC:DTP = 40:1.

[0077] 6 mg of rGO@PDA was dissolved in 2 mL of CMC / DTP mixed solution, ultrasonicated for half an hour, and mixed thoroughly to obtain a mixed solution of rGO@PDA / CMC / DTP.

[0078] 1 mL of the above-mentioned OHA-PBA solution was added to 2 mL of rGO@PDA / CMC / DTP solution and mixed evenly to obtain a self-healing conductive hydrogel immediately, wherein OHA-PBA:CMC:rGO@PDA:DTP =100:200:6:5.

[0079] Example 5

[0080] The rGO@PDA in Example 4 was replaced with GO, and the remaining steps were the same.

[0081] In summary, after adopting the above scheme, the present invention provides a new method for flexible sensors. The hydrogel is linked by multiple dynamic covalent bonds, such as Schiff bases, phenylboronic acid ester bonds, acylhydrazone bonds, etc., which give the hydrogel good self-healing properties and pH sensitivity. The composite rGO@PDA gives the hydrogel good conductive effect and photothermal effect. Based on the self-healing properties of the hydrogel, it can quickly heal itself after damage without affecting its conductive properties. In addition, the pH responsiveness and glucose responsiveness of the hydrogel, as well as good biocompatibility make it of great significance and clinical application value in biomedical flexible sensing. In addition, the drug-carrying function of the hydrogel gives it application prospects in skin treatment and other aspects.

[0082] The above embodiments are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention.

[0083] Figure 1 and Figure 2 The following are the Fourier transform infrared spectra and nuclear magnetic resonance hydrogen spectra of OHA-PBA and HA prepared in Implementation 1-4. Analysis of the infrared spectra shows that compared with the spectrum of HA, the synthesized OHA-PBA has a -1 The C=O aldehyde peak appeared around 1300 cm -1 The BO boron group peak appeared around 4.5-5.0 pm, confirming the successful grafting of phenylboronic acid. Analysis of the H NMR spectrum revealed a chemical shift at around 4.5-5.0 pm for OHA, confirming the successful synthesis of the aldehyde group. The spectrum of OHA-PBA not only exhibited a chemical shift at around 4.5-5.0 pm, but also a shift of hydrogen atoms belonging to the benzene ring at around 7.0-7.5 pm, indicating that both the aldehyde group and phenylboronic acid were successfully grafted.

[0084] Figure 3 This is the compression strength test of Examples 1 to 4. It can be seen from the figure that the hydrogel has good mechanical properties, and its compressive strength increases with the increase of the modified graphene oxide content, and is better than that of the hydrogel compounded with unmodified graphene oxide.

[0085] Figure 4 、 Figure 5 The adhesion properties of Examples 1-4 were demonstrated, and the results showed that the hydrogels all had good adhesion properties, and the adhesion properties increased with the increase of the modified graphene oxide content.

[0086] Figure 6This is the rheological diagram of Example 1. By performing a strain sweep test on the hydrogel, it was found that the hydrogel would break under high strain and heal under low strain. This sol-gel transition proves that the hydrogel has good self-healing properties.

[0087] Figure 7 shows the macroscopic self-healing performance test of Example 1 and Example 4. After the hydrogel was split into two halves, the hydrogels were reattached after standing for a period of time, indicating that the hydrogels have a certain self-healing ability.

[0088] Figure 8 It is the pH sensitivity of the hydrogel. It can be found that the hydrogel can achieve gel-sol-gel transition under the action of HCl and NaOH.

[0089] Figure 9 The antioxidant properties of the hydrogel were tested using the DPPH method. The results showed that the hydrogel had certain antioxidant properties, and the antioxidant properties increased with the increase of the modified graphene oxide content.

[0090] Figure 10 、 11 The conductive properties of the hydrogels in Examples 1-4 were tested using a four-probe method. The results showed that the hydrogels had electrical activity similar to that of the skin, and the conductivity increased with increasing content of modified graphite oxide in the hydrogels.

[0091] Figure 12 、 Figure 13 The photothermal effect of the hydrogel and its antibacterial properties under infrared light were tested respectively. Figure 12 It shows that the hydrogel heats up quickly under light, with the temperature difference reaching up to 40 degrees. Figure 13 It shows that with the increase of illumination time, the bactericidal ability of the hydrogel is enhanced, and complete sterilization can be basically achieved after 15 minutes.

[0092] Figure 14 、 15 The cell compatibility of the hydrogel was tested using CCK8 assay and live-dead staining. The results showed that the hydrogel had a good cell proliferation effect and good cell compatibility.

Claims

1. A method for preparing a conductive hydrogel, characterized in that: The steps include: S1: adding the aldehyde-modified and phenylboronic acid-grafted hyaluronic acid to a phosphate buffer solution to obtain solution A; S2: adding a carboxymethyl chitosan solution and dopamine-modified graphene oxide to a phosphate buffer solution to obtain a solution B; the carboxymethyl chitosan solution is obtained by dissolving carboxymethyl chitosan in a DTP solution, and the DTP solution is obtained by dissolving 3,3'-dithiobis(propionylhydrazide) in a phosphate buffer solution; S3: Mix solution A and solution B evenly and form gel immediately to obtain the conductive hydrogel.

2. The preparation method according to claim 1, characterized in that In step S1, the mass fraction of solution A is 10%-20%; In step S2, the mass fraction of the carboxymethyl chitosan solution is 10%-15%, and the concentration of the dopamine-modified graphene oxide is 1 mg / mL-3 mg / mL; In step S3, the ratio of solution A to solution B is 1:1-1:

2.

3. The preparation method according to claim 1, characterized in that In step S1, the formaldehyde- and phenylboronic acid-grafted hyaluronic acid is prepared by the following steps: S1-1: Add an oxidant to an aqueous solution of hyaluronic acid, allow to react in the dark for 2±1 hours, then add a terminator to terminate the reaction, dialyze, and dry to obtain aldehyde-modified hyaluronic acid; S1-2: Dissolve the aldehyde-modified hyaluronic acid in buffer, add DMTMM and react for 30±10 min, then add 3-aminophenylboronic acid and react for 24±10 h, dialyze, and freeze-dry to obtain aldehyde-modified and phenylboronic acid-grafted hyaluronic acid.

4. The preparation method according to claim 3, characterized in that In step S1-1, the oxidant is sodium periodate and the terminator is ethylene glycol; The mass ratio of hyaluronic acid to oxidant is 1:(0.5~1).

5. The preparation method according to claim 3, characterized in that The buffer in step S1-2 is MES buffer; The mass ratio of aldehyde-modified hyaluronic acid to DMTMM is 1:(0.5~1); The mass ratio of aldehyde-modified hyaluronic acid to 3-aminophenylboronic acid is 1:(0.04~0.1).

6. The preparation method according to claim 1, characterized in that In step S2, the dopamine-modified graphene oxide is prepared by the following steps: dissolving graphene oxide in a buffer solution, then adding dopamine, reacting under nitrogen for 24 hours, centrifuging to obtain a precipitate, washing, and drying to obtain dopamine-modified graphene oxide rGO@PDA.

7. The preparation method according to claim 6, characterized in that In step S2, the buffer used in the preparation of the dopamine-modified graphene oxide is 100 mM Tris-HCl buffer, pH=8.0; the washing is performed multiple times with ethanol and water.

8. The preparation method according to claim 1, characterized in that In step S2, the concentration of the carboxymethyl chitosan solution is (0.1-1) g / mL; the concentration of the DTP solution is 2.5 mg / mL-10 mg / mL.

9. The conductive hydrogel prepared according to the preparation method according to any one of claims 1 to 8.

10. Use of the conductive hydrogel according to claim 9 in a flexible sensor.

Images