CN117065086A

CN117065086A - Multifunctional conductive hydrogel and preparation method and application thereof

Info

Publication number: CN117065086A
Application number: CN202311307170.XA
Authority: CN
Inventors: 章虹; 窦益永; 张育玮
Original assignee: Jinan University
Current assignee: Jinan University
Priority date: 2023-10-10
Filing date: 2023-10-10
Publication date: 2023-11-17

Abstract

The invention provides a multifunctional conductive hydrogel and a preparation method and application thereof, and relates to the field of biomedicine. The preparation method comprises the following raw materials in parts by mass: 5-25 parts of heparin, 0.2-0.8 part of dopamine, 0.5-1.5 part of graphene oxide, 90-110 parts of acrylamide, 3-7 parts of ammonium persulfate, 1.0-1.5 parts of N, N' -methylenebisacrylamide, 0.4-0.8 part of tetramethyl ethylenediamine and 350-400 parts of water. The reduced graphene oxide nanosheets with high reduction degree and high dispersibility are prepared by the polydopamine and heparin synergistic reduction modified graphene oxide, so that the conductive nano composite hydrogel with excellent conductivity, antibacterial activity, oxidation resistance and high biocompatibility is prepared, and the hydrogel can be applied to flexible sensors, catheters, cardiovascular equipment or dressings of diabetic wounds, and can accelerate skin wound healing under the condition of exogenous electrical stimulation.

Description

Multifunctional conductive hydrogel and preparation method and application thereof

Technical Field

The invention relates to the technical field of biomedicine, in particular to a multifunctional conductive hydrogel and a preparation method and application thereof.

Background

The graphene has a unique crystal stable structure in terms of structure and morphological characteristics; meanwhile, the functional groups of the catalyst can be used as covalent/non-covalent modified catalytic active centers. Graphene has excellent electrical, optical, magnetic and thermal properties. Therefore, the graphene material has potential application value in the aspects of flexible sensors and wound dressings.

Graphene Oxide (GO) is used as a raw material, and a physical or chemical method is used to prepare graphene oxide (rGO), which is considered to be the most effective method for producing graphene at low cost and on a large scale, wherein the redox method is one of the best methods. However, the prepared graphene also shows some fatal problems, namely, cytotoxicity exists, so that hemolysis and thrombus formation are caused, and the application of the graphene as biological materials is limited; secondly, agglomeration phenomenon easily occurs, resulting in degradation of electrical and mechanical properties. The above problems are solved by the search of documents to find biomolecules as reducing agents, end-capping agents or stabilizers.

The conductive hydrogel is a soft material with a three-dimensional network structure formed by chemical or physical composite crosslinking of a conductive material and a hydrophilic macromolecule or polymer monomer; the graphene conductive hydrogel is prepared by introducing a graphene nanomaterial on the basis of a hydrogel matrix; the graphene hydrogel has potential application value in the field of flexible sensors. However, the dispersibility of the graphene material in the hydrogel matrix affects the conductivity and mechanical properties of the graphene hydrogel, thereby affecting the sensing performance, which is a non-negligible problem. At present, a great deal of literature reports on preparing polydopamine reduced graphene oxide conductive hydrogel, but common problems of limited reduction degree and dispersibility of polydopamine-graphene nanosheets generally exist, which restrict the preparation of high-sensitivity flexible sensors.

The skin is reported to be sensitive to electrical signals with conductivity values of 10 ^-4 Between 2.6 mS/cm. When the skin is damaged, the micro-current naturally generated by the human body is disturbed, thereby causing the cell to be in disorder. The electrical stimulation can regulate cell behavior and promote wound healing and regeneration. Therefore, the method has potential application value in treating wound healing by simulating micro-current naturally generated by human body through exogenous electric stimulation. How to develop a hydrogel material that is biocompatible, has low biotoxicity and good electrical conductivity, and can be used as a sensor for promoting chronic wound healing is a problem to be solved by the person skilled in the art.

Disclosure of Invention

The invention aims to provide a multifunctional conductive hydrogel and a preparation method and application thereof, so as to solve the problems of poor conductivity, poor biocompatibility, biotoxicity and the like of a material caused by low reduction degree and poor dispersibility of graphene in a gel material in the conventional conductive gel material.

In order to achieve the above object, the present invention provides the following technical solutions:

the invention provides a multifunctional conductive hydrogel which is prepared from the following raw materials in parts by weight: 5-25 parts of heparin, 0.2-0.8 part of dopamine, 0.5-1.5 part of graphene oxide, 90-110 parts of acrylamide, 3-7 parts of ammonium persulfate, 1.0-1.5 parts of N, N' -methylenebisacrylamide, 0.4-0.8 part of tetramethyl ethylenediamine and 350-400 parts of water.

The invention provides a preparation method of a multifunctional conductive hydrogel, which comprises the following steps:

1) Regulating the pH value of the dopamine aqueous solution, then mixing with heparin, and reacting to obtain a Hep-PDA compound;

2) Mixing graphene oxide aqueous dispersion liquid with a Hep-PDA compound, and reacting to obtain a mixed liquid containing Hep-PDA-rGO;

3) And mixing the mixed solution containing the Hep-PDA-rGO with acrylamide, ammonium persulfate, N' -methylene bisacrylamide and tetramethyl ethylenediamine for reaction to obtain a pre-polymerized solution, and solidifying and molding the pre-polymerized solution to obtain the multifunctional conductive hydrogel.

Preferably, the reaction in the step 1) is performed under the condition of stirring, and the reaction time is 15-20 min;

and adjusting the pH value of the aqueous solution of dopamine to 10-11.

Preferably, the reaction in the step 2) is performed under the condition of stirring, and the reaction time is 15-20 min.

Preferably, the reaction in the step 3) is performed in an ice-water bath, and the reaction time is 20-40 s.

The invention also provides a preparation method of the multifunctional conductive hydrogel, which comprises the following steps:

1) Mixing heparin aqueous solution with graphene oxide aqueous dispersion, and stirring for reaction to obtain Hep-rGO dispersion;

2) Regulating the pH value of the dopamine aqueous solution, performing oxidation self-polymerization reaction, then adding a Hep-rGO dispersion liquid, and performing reduction reaction to obtain a mixed liquid containing Hep-PDA-rGO;

3) Adding acrylamide, ammonium persulfate, N' -methylene bisacrylamide and tetramethyl ethylenediamine into the mixed solution containing the Hep-PDA-rGO to react to obtain a prepolymer, and solidifying and molding the prepolymer to obtain the multifunctional conductive hydrogel.

Preferably, the stirring speed in the step 1) is 400-600 r/min, and the reaction time is 15-25 min.

Preferably, the time of the oxidation self-polymerization reaction in the step 2) is 15-25 min;

and adjusting the pH value of the aqueous solution of dopamine to 10-11.

The reduction reaction is carried out under the condition of stirring, and the stirring speed is 400-600 r/min; the reduction reaction time is 10-20 min.

The invention provides application of multifunctional conductive hydrogel in the field of biomedicine.

The invention has at least the following beneficial effects:

1. according to the invention, the reduction reaction time and the reducing agent are improved, wherein after the heparin and the polydopamine are compounded, the polydopamine can be used as the reducing agent, and the heparin can be used as the dispersing agent, so that the reduction degree and biocompatibility of graphene are effectively improved, and the problem that graphene is easy to agglomerate in a hydrogel matrix is solved, so that the conductivity of the graphene hydrogel is greatly improved.

2. The graphene-containing hydrogel prepared by the invention has more excellent sensing performance and mechanical performance, and can be used as a flexible sensor for monitoring human body movement in real time.

3. The graphene-containing hydrogel based on flexible sensing and chronic wound healing has good biocompatibility, antibacterial property and oxidation resistance, can be applied to flexible sensors, catheters, cardiovascular equipment or dressings of diabetic wounds, and can accelerate skin wound healing under the condition of exogenous electrical stimulation.

Drawings

FIG. 1 is a graph showing the dispersion state of nano-sheets of different components in water with time;

FIG. 2 is a scanning electron microscope image of the hydrogel prepared by the invention, wherein a is a scanning electron microscope image of GO-PAM, and b is a Hep ₂₀ Scanning electron microscope image of-rGO-PAM, c is PDA _0.8 Scanning electron microscope image of-rGO-PAM, d is Hep ₂₀ -PDA _0.2 Scanning electron microscope image of-rGO-PAM, e is Hep ₂₀ -PDA _0.4 Scanning electron microscope image of-rGO-PAM, f is Hep ₂₀ -PDA _0.8 -scanning electron microscopy of rGO-PAM;

FIG. 3 is a graph showing the sterilization rate of hydrogels prepared according to the present invention;

FIG. 4 is a graph showing the results of an antibacterial experiment on a hydrogel prepared according to the present invention, wherein a is the growth of Staphylococcus aureus on a blank culture substrate, and b is the growth of Staphylococcus aureus on a culture substrate containing Hep ₂₀ -PDA _0.2 Growth on culture substrate of rGO-PAM hydrogel, c is Staphylococcus aureus and Hep ₂₀ -PDA _0.4 -rGO-PAM hydrogel co-cultured for 4 hours, d is staphylococcus aureus and Hep ₂₀ -PDA _0.8 -rGO-PAM hydrogel co-cultured for 4 hours, e is the growth of Pseudomonas aeruginosa on blank culture substrate, and f is Pseudomonas aeruginosa and Hep ₂₀ -PDA _0.2 Growth after 4 hours of co-culture of rGO-PAM hydrogel, g is Pseudomonas aeruginosa and Hep ₂₀ -PDA _0.4 Growth of rGO-PAM hydrogel 4 hours after co-culture, h is Pseudomonas aeruginosa and Hep ₂₀ -PDA _0.8 -growth after 4 hours of co-culture of rGO-PAM hydrogel;

FIG. 5 is a diagram showing the movement of a monitored human body, wherein a is a diagram showing the movement of the monitored human body, b is a curve of the resistance change rate-time of the finger when the finger is bent at different angles, c is a curve of the resistance change rate-time of the finger when the finger is bent at different angles for multiple cycles, d is a curve of the resistance change rate-time of the elbow when the finger is bent at multiple cycles, e is a curve of the resistance change rate-time of the knee when the knee is bent at multiple cycles, and f is a curve of the resistance change rate-time of the running on walking;

fig. 6 is a graph of promoting diabetic wound healing under electrical stimulation, wherein a is a schematic diagram of wound generation and electrical stimulation treatment process, b is a graph of chronic wound healing of diabetes on days 0, 3, 7 and 14, c is a graph of wound healing of an electrical stimulation rat, and d is a graph of wound closure rate in different time periods.

Detailed Description

The invention provides a multifunctional conductive hydrogel which is prepared from the following raw materials in parts by weight: 5-25 parts of heparin, 0.2-0.8 part of dopamine, 0.5-1.5 part of graphene oxide, 90-110 parts of acrylamide, 3-7 parts of ammonium persulfate, 1.0-1.5 parts of N, N' -methylenebisacrylamide, 0.4-0.8 part of tetramethyl ethylenediamine and 350-400 parts of water; the compound comprises, by weight, 17-23 parts of heparin, 0.3-0.7 part of dopamine, 0.7-1.3 parts of graphene oxide, 93-107 parts of acrylamide, 3.5-6.5 parts of ammonium persulfate, 1.1-1.4 parts of N, N' -methylenebisacrylamide, 0.5-0.8 part of tetramethyl ethylenediamine and 355-395 parts of water; further preferably 19-21 parts of heparin, 0.4-0.6 part of dopamine, 0.9-1.1 part of graphene oxide, 95-105 parts of acrylamide, 4-6 parts of ammonium persulfate, 1.2-1.3 parts of N, N' -methylenebisacrylamide, 0.6-0.7 part of tetramethyl ethylenediamine and 360-390 parts of water; more preferably, the composition comprises 20 parts of heparin, 0.5 part of dopamine, 1.0 part of graphene oxide, 98-102 parts of acrylamide, 5 parts of ammonium persulfate, 1.25 parts of N, N' -methylenebisacrylamide, 0.6-0.7 part of tetramethyl ethylenediamine and 370-380 parts of water.

In the invention, the reaction in the step 1) is carried out under the condition of stirring, and the reaction time is 15-20 min, preferably 16-19 min, and more preferably 17-18 min; the stirring speed is 200-800 r/min, preferably 400-600 r/min, and more preferably 450-550 r/min.

In the invention, the pH value of the dopamine aqueous solution is preferably adjusted to 10-11 by adopting NaOH solution, and the pH value is further preferably adjusted to 11.

In the present invention, the concentration of the aqueous solution of dopamine is 0.5 to 4.0mg/mL, preferably 1.0 to 3.5mg/mL, more preferably 1.5 to 3.0mg/mL, and even more preferably 2.0 to 2.5mg/mL.

In the invention, the reaction in the step 2) is carried out under the condition of stirring, wherein the stirring speed is 400-600 r/min, preferably 450-550 r/min, more preferably 480-530 r/min, and even more preferably 500-510 r/min; the reaction time is 15 to 20 minutes, preferably 16 to 19 minutes, and more preferably 17 to 18 minutes.

In the invention, the concentration of the graphene oxide aqueous dispersion is 1.5-10 mg/mL, preferably 2.5-7.5 mg/mL, more preferably 4-6 mg/mL, and even more preferably 4.5-5.5 mg/mL.

In the present invention, the reaction in the step 3) is performed in an ice-water bath for 20 to 40 seconds, preferably 25 to 35 seconds, more preferably 28 to 32 seconds, and still more preferably 30 seconds.

In the present invention, the raw materials such as acrylamide, ammonium persulfate, N' -methylenebisacrylamide, tetramethylethylenediamine, etc. in the step 3) are preferably added sequentially, and stirred for 1 to 6 minutes, preferably for 2 to 4 minutes, after each raw material is added.

In the invention, the stirring speed in the step 1) is 400-600 r/min, preferably 450-550 r/min, more preferably 480-530 r/min, and even more preferably 500-510 r/min; the reaction time is 15 to 25 minutes, preferably 17 to 23 minutes, more preferably 19 to 21 minutes, and even more preferably 20 minutes.

In the invention, the concentration of the heparin aqueous solution is 30-100 mg/mL, preferably 40-90 mg/mL, more preferably 50-80 mg/mL, and even more preferably 60-70 mg/mL; the concentration of the graphene oxide aqueous dispersion solution is 1.5-10 mg/mL, preferably 2.5-7.5 mg/mL, more preferably 4-6 mg/mL, and even more preferably 4.5-5.5 mg/mL.

In the present invention, the time of the oxidative auto-polymerization reaction in the step 2) is 15 to 25 minutes, preferably 17 to 23 minutes, more preferably 19 to 21 minutes, and even more preferably 20 minutes.

The pH value of the dopamine aqueous solution is preferably adjusted to 10-11 by adopting a NaOH solution.

In the invention, the reduction reaction is carried out under the condition of stirring, wherein the stirring speed is 400-600 r/min, preferably 450-550 r/min, more preferably 480-530 r/min, and more preferably 500-510 r/min; the reduction reaction time is 5 to 15 minutes, preferably 7 to 13 minutes, more preferably 8 to 11 minutes, and still more preferably 9 to 10 minutes.

In the invention, the concentration of the aqueous solution of dopamine is 5-40 mg/mL, preferably 10-35 mg/mL, more preferably 15-30 mg/mL, and even more preferably 20-25 mg/mL.

The invention also provides application of the multifunctional conductive hydrogel in the biomedical field, in particular application of the multifunctional conductive hydrogel in preparing wound dressing and flexible sensor.

The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.

Example 1

25mg of Graphene Oxide (GO) and 4.5mL of water are mixed, ultrasonically stirred and dispersed for 30min, and GO dispersion is obtained.

Dissolving 5mg of Dopamine (DA) in 5mL of water, stirring for 10min, adding 500 mu L of 1mol/L NaOH solution to adjust the pH value of the system to 11, stirring again for 20min for oxidation self-polymerization to obtain PDA, adding 500mg of heparin (Hep), and stirring at a rotating speed of 500r/min for 20min to obtain a Hep-PDA compound.

The GO dispersion was mixed with the Hep-PDA complex and stirred for 20min before the following operations were performed in sequence: 2.5g of acrylamide was added and stirred for 6 minutes, 125mg of ammonium persulfate was added and stirred for 2 minutes, and 30mg of N, N' -methylenebisacryloyl was addedAmine stirring for 3min, adding 20 μL of tetramethyl ethylenediamine ice bath stirring for 30s to obtain a pre-polymerization solution, pouring the pre-polymerization solution into a mold, solidifying and molding to obtain multifunctional conductive hydrogel, wherein Hep accounts for 20% of the mass of acrylamide, DA accounts for 0.2% of the mass of acrylamide, and the hydrogel material can be written as Hep ₂₀ -PDA _0.2 -rGO-PAM。

Example 2

Dissolving 10mg of Dopamine (DA) in 5mL of water, stirring for 10min, adding 500 mu L of 1mol/L NaOH solution to adjust the pH value of the system to 11, stirring again for 20min to perform oxidation self-polymerization to obtain PDA, adding 500mgHep, and stirring at a rotating speed of 500r/min for 20min to obtain a Hep-PDA compound.

The GO dispersion was mixed with the Hep-PDA complex and stirred for 20min before the following operations were performed in sequence: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mould, and solidifying and molding to obtain the multifunctional conductive hydrogel, wherein Hep accounts for 20% of the mass of the acrylamide, DA accounts for 0.4% of the mass of the acrylamide, and the hydrogel material can be written as Hep ₂₀ -PDA _0.4 -rGO-PAM。

Example 3

Dissolving 20mg of Dopamine (DA) in 5mL of water, stirring for 10min, adding 500 mu L of 1mol/L NaOH solution to adjust the pH value of the system to 11, stirring for 20min again to perform oxidation self-polymerization to obtain PDA, adding 500mgHep, and stirring for 20min at a rotating speed of 500r/min to obtain the Hep-PDA compound.

The GO dispersion was mixed with the Hep-PDA complex and stirred for 20min before the following operations were performed in sequence: 2.5g of acrylamide is added and stirred for 6min, 125mg of ammonium persulfate is added and stirred for 2min, 30mgN, N' -methylene bisacrylamide is added and stirred for 3min, 20 mu L of tetramethyl ethylenediamine is added and stirred for 30s in an ice bath to obtain a prepolymer,pouring the prepolymer into a mould to solidify and form a multifunctional conductive hydrogel, wherein the Hep accounts for 20% of the mass of the acrylamide, the DA accounts for 0.8% of the mass of the acrylamide, and the hydrogel material can be written as Hep ₂₀ -PDA _0.8 -rGO-PAM。

Example 4

20mg of Graphene Oxide (GO) and 5mL of water are mixed, ultrasonically stirred and dispersed for 30min, and GO dispersion is obtained.

Dissolving 10mg of Dopamine (DA) in 4mL of water, stirring for 10min, adding a NaOH solution to adjust the pH value of the system to 11, stirring again for 20min to perform oxidation self-polymerization to obtain PDA, adding 200mg of Hep, and stirring at a rotating speed of 500r/min for 20min to obtain a Hep-PDA compound.

The GO dispersion was mixed with the Hep-PDA complex and stirred for 20min before the following operations were performed in sequence: 2.5g of acrylamide is added and stirred for 6min, 120mg of ammonium persulfate is added and stirred for 2min, 32mgN, N' -methylene bisacrylamide is added and stirred for 3min, 20 mu L of tetramethyl ethylenediamine is added and stirred for 30s in an ice bath to obtain a prepolymer solution, and the prepolymer solution is poured into a mold to be solidified and molded to obtain the multifunctional conductive hydrogel.

Example 5

13mg of Graphene Oxide (GO) and 3.5mL of water are mixed, ultrasonically stirred and dispersed for 30min, and GO dispersion is obtained.

Dissolving 20mg of Dopamine (DA) in 5mL of water, stirring for 10min, adding 500 mu L of 1mol/L NaOH solution to adjust the pH value of the system to 11, stirring for 20min again to perform oxidation self-polymerization to obtain PDA, adding 125mgHep, and stirring at a rotating speed of 500r/min for 20min to obtain a Hep-PDA compound.

The GO dispersion was mixed with the Hep-PDA complex and stirred for 20min before the following operations were performed in sequence: 2.5g of acrylamide is added and stirred for 6min, 115mg of ammonium persulfate is added and stirred for 2min, 26mgN, N' -methylene bisacrylamide is added and stirred for 3min, 18 mu L of tetramethyl ethylenediamine is added and stirred for 30s in an ice bath to obtain a prepolymer solution, and the prepolymer solution is poured into a mold to be solidified and molded to obtain the multifunctional conductive hydrogel.

Example 6

500mgHep was dissolved in 6.0mL of water to obtain a Hep solution; mixing 25mgGO with 3.0mL of water, and performing ultrasonic dispersion for 30min to obtain GO dispersion; mixing heparin solution and GO dispersion liquid, stirring for 20min under the condition of 600r/min, and carrying out reduction reaction to obtain Hep-rGO dispersion liquid.

Dissolving 5mgDA in 0.5mL of water, adding NaOH solution to adjust the pH of the system to 11, stirring at 500r/min for 20min to perform oxidation self-polymerization reaction to obtain PDA solution, adding Hep-rGO dispersion liquid, stirring at 500r/min for 10min, and performing reduction reaction to obtain Hep-PDA-rGO. The following operations are then carried out in sequence: 2.5g of acrylamide is added into Hep-PDA-rGO, stirring is carried out for 6min, 130mg of ammonium persulfate is added, stirring is carried out for 2min, 30mgN, N' -methylene bisacrylamide is added, stirring is carried out for 3min, 20 mu L of tetramethyl ethylenediamine is added, ice bath stirring is carried out for 30s, thus obtaining a prepolymer solution, and the prepolymer solution is poured into a mould for solidification and molding, thus obtaining the multifunctional conductive hydrogel.

Example 7

500mgHep was dissolved in 5.0mL of water to obtain a Hep solution; mixing 25mgGO with 4.0mL of water, and performing ultrasonic dispersion for 30min to obtain GO dispersion; mixing heparin solution and GO dispersion liquid, stirring for 15min at 600r/min, and carrying out reduction reaction to obtain Hep-rGO dispersion liquid.

Dissolving 10mgDA in 0.5mL of water, adding NaOH solution to adjust the pH of the system to 11, stirring at a rotation speed of 500r/min for 20min to perform oxidation self-polymerization reaction to obtain PDA solution, adding Hep-rGO dispersion liquid, stirring at a rotation speed of 400r/min for 8min, and performing reduction reaction to obtain Hep-PDA-rGO. The following operations are then carried out in sequence: 2.5g of acrylamide is added into Hep-PDA-rGO, stirring is carried out for 6min, 125mg of ammonium persulfate is added, stirring is carried out for 2min, 28mgN, N' -methylene bisacrylamide is added, stirring is carried out for 3min, 22 mu L of tetramethyl ethylenediamine is added, ice bath stirring is carried out for 30s, thus obtaining a prepolymer solution, and the prepolymer solution is poured into a mould for solidification and molding, thus obtaining the multifunctional conductive hydrogel.

Example 8

500mgHep was dissolved in 5.0mL of water to obtain a Hep solution; mixing 25mgGO with 4.0mL of water, and performing ultrasonic dispersion for 30min to obtain GO dispersion; mixing heparin solution and GO dispersion liquid, stirring for 20min under the condition of 600r/min, and carrying out reduction reaction to obtain Hep-rGO dispersion liquid.

Dissolving 20mgDA in 0.5mL of water, adding NaOH solution to adjust the pH of the system to 11, stirring for 20min at the rotation speed of 500r/min to perform oxidation self-polymerization reaction to obtain PDA solution, adding Hep-rGO dispersion liquid, stirring for 10min at the rotation speed of 500r/min, and performing reduction reaction to obtain Hep-PDA-rGO. The following operations are then carried out in sequence: 2.5g of acrylamide is added into Hep-PDA-rGO, stirring is carried out for 6min, 125mg of ammonium persulfate is added, stirring is carried out for 2min, 30mgN, N' -methylene bisacrylamide is added, stirring is carried out for 3min, 17 mu L of tetramethyl ethylenediamine is added, ice bath stirring is carried out for 30s, thus obtaining a prepolymer solution, and the prepolymer solution is poured into a mould for solidification and molding, thus obtaining the multifunctional conductive hydrogel.

Example 9

125mgHep was dissolved in 4.0mL of water to obtain a Hep solution; mixing 25mgGO with 4.0mL of water, and performing ultrasonic dispersion for 30min to obtain GO dispersion; mixing heparin solution and GO dispersion liquid, stirring for 20min under the condition of 600r/min, and carrying out reduction reaction to obtain Hep-rGO dispersion liquid.

Dissolving 20mgDA in 0.5mL of water, adding NaOH solution to adjust the pH of the system to 11, stirring for 20min at the rotation speed of 500r/min to perform oxidation self-polymerization reaction to obtain PDA solution, adding Hep-rGO dispersion liquid, stirring for 10min at the rotation speed of 500r/min, and performing reduction reaction to obtain Hep-PDA-rGO. The following operations are then carried out in sequence: 2.5g of acrylamide is added into Hep-PDA-rGO, stirring is carried out for 6min, 130mg of ammonium persulfate is added, stirring is carried out for 2min, 30mgN, N' -methylene bisacrylamide is added, stirring is carried out for 3min, 20 mu L of tetramethyl ethylenediamine is added, ice bath stirring is carried out for 30s, thus obtaining a prepolymer solution, and the prepolymer solution is poured into a mould for solidification and molding, thus obtaining the multifunctional conductive hydrogel.

Example 10

250mgHep was dissolved in 5.0mL of water to obtain a Hep solution; mixing 25mgGO with 4.0mL of water, and performing ultrasonic dispersion for 30min to obtain GO dispersion; mixing heparin solution and GO dispersion liquid, stirring for 20min under the condition of 600r/min, and carrying out reduction reaction to obtain Hep-rGO dispersion liquid.

Dissolving 20mgDA in 0.5mL of water, adding NaOH solution to adjust the pH of the system to 11, stirring for 20min at the rotation speed of 500r/min to perform oxidation self-polymerization reaction to obtain PDA solution, adding Hep-rGO dispersion liquid, stirring for 10min at the rotation speed of 500r/min, and performing reduction reaction to obtain Hep-PDA-rGO. The following operations are then carried out in sequence: 2.5g of acrylamide is added into Hep-PDA-rGO, stirring is carried out for 6min, 125mg of ammonium persulfate is added, stirring is carried out for 2min, 30mgN, N' -methylene bisacrylamide is added, stirring is carried out for 3min, 20 mu L of tetramethyl ethylenediamine is added, ice bath stirring is carried out for 30s, thus obtaining a prepolymer solution, and the prepolymer solution is poured into a mould for solidification and molding, thus obtaining the multifunctional conductive hydrogel.

Comparative example 1

2.5g of acrylamide was mixed with 10mL of water and stirred at 500r/min for 6min, followed in this order by the following operations: 125mg of ammonium persulfate is added and stirred for 2min, 30mgN, N' -methylene bisacrylamide is added and stirred for 3min, 20 mu L of tetramethyl ethylenediamine is added and stirred for 30s in an ice bath to obtain a prepolymer liquid, and the prepolymer liquid is poured into a mould to be solidified and molded to obtain the PAM hydrogel material.

Comparative example 2

After mixing 25mgGO with 10mL of water and ultrasonic dispersing for half an hour, the following operations are sequentially performed: 2.5g of acrylamide is added and stirred for 6min, 125mg of ammonium persulfate is added and stirred for 2min, 30mgN, N' -methylene bisacrylamide is added and stirred for 3min, 20 mu L of tetramethyl ethylenediamine is added and stirred for 30s in an ice bath to obtain a prepolymer solution, and the prepolymer solution is poured into a mold to be solidified and molded to obtain the GO-PAM hydrogel material.

Comparative example 3

25mgGO was mixed with 10mL of water, dispersed by sonication for half an hour, 125mgHep was added, followed by the following operations in order: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain Hep ₅ -rGO-PAM hydrogel material.

Comparative example 4

25mgGO was mixed with 10mL of water, dispersed by sonication for half an hour, 250mgHep was added, and then the following operations were performed sequentially: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain Hep ₁₀ -rGO-PAM hydrogel material.

Comparative example 5

25mgGO is mixed with 10mL of water, after half an hour of ultrasonic dispersion, 500mgHep is added, and then the following operations are sequentially carried out: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain Hep ₂₀ -rGO-PAM hydrogel material.

Comparative example 6

Mixing 25mgGO with 4.5mL of water, and performing ultrasonic dispersion for 30min; mixing 5mgDA and 5mL of water, stirring for 10min, adding 50 mu LNaOH solution to adjust the pH value to 11, stirring for 20min to perform oxidation self-polymerization to obtain PDA solution, adding GO dispersion liquid into the PDA solution, stirring for 20min, performing reduction reaction to obtain PDA-rGO, and then sequentially performing the following operations: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain PDA _0.2 -rGO-PAM hydrogel material.

Comparative example 7

Mixing 25mgGO with 4.5mL of water, and performing ultrasonic dispersion for 30min; mixing 10mgDA and 5mL of water, stirring for 10min, adding 50 mu LNaOH solution to adjust the pH value to 11, stirring for 20min to perform oxidation self-polymerization to obtain PDA solution, adding GO dispersion liquid into the PDA solution, stirring for 20min, performing reduction reaction to obtain PDA-rGO, and then sequentially performing the following operations: adding 2.5g of acrylamide, stirring for 6min, adding 125mg of ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 mu L of tetramethyl ethylenediamine, stirring for 30s in an ice bath to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain PDA _0.4 -rGO-PAM hydrogel material.

Comparative example 8

Mixing 25mgGO with 4.5mL of water, and performing ultrasonic dispersion for 30min; mixing 20mgDA and 5mL of water, stirring for 10min, adding 50 mu LNaOH solution to adjust the pH value to 11, stirring for 20min to perform oxidation self-polymerization to obtain PDA solution, adding GO dispersion liquid into the PDA solution, stirring for 20min, performing reduction reaction to obtain PDA-rGO, and then sequentially performing the following operations: add 2.5Stirring g acrylamide for 6min, adding 125mg ammonium persulfate, stirring for 2min, adding 30mgN, N' -methylenebisacrylamide, stirring for 3min, adding 20 μl tetramethylethylenediamine ice bath, stirring for 30s to obtain a prepolymer solution, pouring the prepolymer solution into a mold, and solidifying and molding to obtain PDA _0.8 -rGO-PAM hydrogel material.

In the preparation methods described in examples 1 to 3 and comparative examples 2 to 8, the subsequent steps of adding acrylamide, ammonium persulfate, N' -methylenebisacrylamide and tetramethylethylenediamine and solidifying and molding are omitted to obtain corresponding nano-sheet dispersion liquid, which is in turn Hep ₂₀ -PDA _0.2 -rGO、Hep ₂₀ -PDA _0.4 -rGO、Hep ₂₀ -PDA _0.8 -rGO、GO、Hep ₅ -rGO、Hep ₁₀ -rGO、Hep ₂₀ -rGO、PDA _0.2 -rGO、PDA _0.4 -rGO and PDA _0.8 The rGO nano-sheet dispersion liquid is placed in a centrifuge tube for standing for 90 days, the result of photographing record is shown as figure 1, and GO and Hep are sequentially arranged in the centrifuge tube from left to right in figure 1 ₅ -rGO、Hep ₁₀ -rGO、Hep ₂₀ -rGO、Hep ₂₀ -PDA _0.2 -rGO、Hep ₂₀ -PDA _0.4 -rGO、Hep ₂₀ -PDA _0.8 -rGO、PDA _0.2 -rGO、PDA _0.4 -rGO、PDA _0.8 An aqueous dispersion of rGO, from figure 1, it can be seen that the Hep-PDA-rGO group is darker relative to the Hep-rGO and PDA-rGO groups, which laterally demonstrates that Hep and PDA can effectively co-reduce GO, with the Hep-PDA-rGO group having the highest degree of reduction. According to potential and particle size tests, the GO nano-sheets are negatively charged, the Hep can be adsorbed on rGO to form a Hep-rGO compound with larger particle size, and the Hep has abundant negative charge groups, so that the potential of particles in a system is increased, the repulsion between the particles is increased due to the strong electrostatic effect, and the aggregation of the rGO nano-sheets can be effectively prevented; the PDA-rGO solution had agglomerated and settled on the third day and PDA on the seventh day _0.8 The rGO is completely agglomerated and settled, and the stability is poor; except that under the electrostatic stabilization of the Hep-PDA complex, hep ₂₀ -PDA _0.8 The rGO solution is stable for at least 90 days, since the adhesion of the PDA is such thatHep adsorbs better on both sides of the rGO surface.

FIG. 2 is a scanning electron microscope image of graphene hydrogel prepared by the method, wherein images a-f are GO-PAM (a) and Hep in sequence ₂₀ -rGO-PAM(b)、PDA _0.8 -rGO-PAM(c)、Hep ₂₀ -PDA _0.2 -rGO-PAM(d)、Hep ₂₀ -PDA _0.4 -rGO-PAM(e)、Hep ₂₀ -PDA _0.8 -rGO-PAM (f), it can be seen from a in fig. 2 that the GO-PAM hydrogel has a uniform lamellar structure and smooth pore walls; in Hep-rGO-PAM hydrogels, hep attaches to rGO surface through non-covalent interactions, making the overall network compact; although the microstructure of the PDA-rGO-PAM hydrogel is compact, the dispersion among rGO is poor, aggregation occurs, the lamellar structures are mutually stacked, and the mechanical property and the electric conductivity of the formed hydrogel can be influenced; however, aggregation between rGO was seen to reduce the stacking of lamellar structures by the Hep-PDA-rGO-PAM hydrogels (d, e, f in FIG. 2), indicating that Hep acts as a dispersant therein ₂₀ -PDA _0.8 The conductive network structure of the rGO-PAM hydrogel is more compact and complete.

For the Hep prepared in examples 1 to 3 ₂₀ -PDA _0.2 -rGO-PAM、Hep ₂₀ -PDA _0.4 -rGO-PAM、Hep ₂₀ -PDA _0.8 The antibacterial property of the rGO-PAM hydrogel material is tested by the following specific test method: the test was performed using Pseudomonas aeruginosa and Staphylococcus aureus from Guangdong Cryptographic microorganism technologies Co. And the antibacterial performance of the hydrogel is verified by adopting a plate colony counting method, and the hydrogel prepared in the examples 1-3 is used as an experimental group and a blank (anhydrous gel sample) is used as a control group. 4 replicates of each group were used for the antimicrobial test. All bacteria were cultured in Luria-Bertani broth. 10 mu L of two bacterial suspensions (10) ⁸ CFU/mL) was added dropwise to the surfaces of the three hydrogel materials of uniform size, and the humidity was kept at 90% or higher to prevent evaporation of the bacterial liquid, and co-culture was carried out at 37 ℃ for 4 hours. After 4 hours, bacteria on the hydrogel surface were rinsed off with 1ml pbs; then ultrasonic treatment is carried out for 5min, and bacteria attached to the surface of the hydrogel are fully oscillated; then dissolveThe liquid is subjected to gradient dilution to 10 ⁴ CFU/mL was added to the agar plate 100. Mu.L of the gradient diluted solution, the applicator was spread evenly, and the solution was placed in a bacterial incubator at 37℃for 24 hours, and the photographed count was taken out, and the result is shown in FIG. 4. The sterilization capacity of the Hep-PDA-rGO-PAM hydrogel reaches more than 90%, and the sterilization efficiency trend is consistent with a flat-plate coating graph; in contrast to the blank, hep ₂₀ -PDA _0.8 The killing rate of the rGO-PAM hydrogel to staphylococcus aureus is 99.7 percent and the killing rate to staphylococcus aureus is 99.81 percent.

The hydrogel sample is fixed on a human body monitoring part such as a finger, a knee, a throat and the like through a conductive adhesive tape, and is connected with an electrochemical workstation through the conductive hydrogel, the working mode of the electrochemical workstation is set to be i-t, the voltage is 1.0V, and current data are recorded in real time. The current data are shown as a-f in figure 5 and are respectively delta R/R for monitoring human motion schematic diagrams, fingers, multiple times of cyclic bending of fingers with different angles, multiple times of cyclic bending of elbows, multiple times of cyclic bending of knees and walking running ₀ (%) time curve (rate of change of resistance versus time line). Firstly, adhering a hydrogel flexible sensor to a finger to perform bending preliminary monitoring at different angles and analyzing an obtained resistance change rate relation graph (b in fig. 5), wherein the finger is correspondingly displayed with different resistance change rates at different angles; the finger bends 45 degrees and 90 degrees circularly to perform periodic movement (b in fig. 5), the hydrogel sensor can clearly distinguish the bending and loosening of the finger, and the resistance change rate also performs stable periodic change; in addition, the conductive hydrogel sensor, when attached to the elbow and knee for cyclic flexion (c in fig. 5, d in fig. 5), also rapidly exhibits a smooth, highly reproducible signal response. The hydrogel sensor not only has tensile sensitivity, but also can be used as a tensile strain sensor, can monitor compressive movement based on high compressive sensitivity, and can realize accurate identification of walking and running of a human being according to the differential frequency of resistance change and the waveform of a signal as shown in e in fig. 5.

15 healthy male white closed group rats are selected, and the weight of the rats is 220-250 g and the age is 7-8 weeks. Randomly, 5 groups of 3 rats were housed, 3 rats/cage fed, and were fed and drunk freely. Each rat was acclimatized for one week. After 12 hours of overnight fast, streptozotocin (60 mg/kg body weight) was intravenously injected into male SD rats (250-300 g) to induce type II diabetes mellitus, and blood glucose levels in tail vein blood were monitored with a blood glucose meter. Until the blood glucose level exceeded 16.67mM, it was considered that the type II diabetes rat model was successfully established. After successful modeling (i.e. blood glucose levels exceeding 16.67 mM), the backs of each rat were dehaired and sterilized by anesthesia with 10% (w/v) chloral hydrate (0.3 mL/100g body weight), and then four square full thickness wounds (.about.1X1 cm) were formed in the backs of each rat. Each wound was inoculated with 50. Mu.L of 1X 10 ⁸ CUF/mL bacterial suspension of Staphylococcus aureus. These wounds were divided into five groups, blank: treating the wound surface with physiological saline; control group: AQUACEL (AQUACL) ^® Series of Ag ⁺ Dressing; experimental group: 1. the wound surface covered by the GO-PAM hydrogel is marked as a GO group; 2. with Hep having optimal antibacterial and antioxidant properties and optimal biocompatibility ₂₀ -PDA _0.8 The wound covered by rGO-PAM hydrogel is marked as rGO group; 3. by Hep ₂₀ -PDA _0.8 The wound surface covered by rGO-PAM hydrogel is recorded as rGO+ES group, which is stimulated with 100mv/mm DC voltage for 1h every day. Commercial dressing sets dressing changes weekly during the healing process. Wound size was measured by tracking wound boundaries at predetermined time intervals for the wound 0, 1, 3, 7, 14 days after injury. Wound changes are shown in FIG. 6, from which it can be seen that the rGO group is a Hep made by the present invention ₂₀ -PDA _0.8 The rGO-PAM hydrogel covers the wound surface, the wound surface heals faster, and the wound surface is more commercial Ag after fourteen days ⁺ The wound surface covered by the dressing is small, which shows that the hydrogel dressing prepared by the invention has a certain effect of promoting wound healing; in addition, the rGO+ES group is stimulated for 1h by 100mv/mm direct current voltage every day, and the wound almost completely heals after fourteen days, which shows that the gel material disclosed by the invention can be matched with electric stimulation to promote the chronic wound healing of the diabetic mice.

The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.

Claims

1. The multifunctional conductive hydrogel is characterized by being prepared from the following raw materials in parts by weight: 5-25 parts of heparin, 0.2-0.8 part of dopamine, 0.5-1.5 part of graphene oxide, 90-110 parts of acrylamide, 3-7 parts of ammonium persulfate, 1.0-1.5 parts of N, N' -methylenebisacrylamide, 0.4-0.8 part of tetramethyl ethylenediamine and 350-400 parts of water.

2. The method for preparing the multifunctional conductive hydrogel as set forth in claim 1, comprising the steps of:

3. The method for preparing the multifunctional conductive hydrogel according to claim 2, wherein the reaction in the step 1) is performed under the condition of stirring, and the reaction time is 15-20 min;

and adjusting the pH value of the aqueous solution of dopamine to 10-11.

4. The method for preparing a multifunctional conductive hydrogel according to claim 3, wherein the reaction in the step 2) is performed under stirring, and the reaction time is 15-20 min.

5. The method for preparing a multifunctional conductive hydrogel according to claim 3 or 4, wherein the reaction in the step 3) is performed in an ice-water bath, and the reaction time is 20-40 s.

6. The method for preparing the multifunctional conductive hydrogel as set forth in claim 1, comprising the steps of:

7. The method for preparing the multifunctional conductive hydrogel according to claim 6, wherein the stirring speed in the step 1) is 400-600 r/min, and the reaction time is 15-25 min.

8. The method for preparing a multifunctional conductive hydrogel according to claim 7, wherein the time of the oxidative autopolymerization reaction in the step 2) is 15-25 min;

the pH value of the dopamine aqueous solution is adjusted to 10-11;

9. The method for preparing the multifunctional conductive hydrogel according to claim 8, wherein the reaction in the step 3) is performed in an ice-water bath, and the reaction time is 20-40 s.

10. Use of a multifunctional conductive hydrogel according to claim 1 in the biomedical field.