CN110117369B

CN110117369B - Antibacterial adhesive conductive hydrogel and preparation method and application thereof

Info

Publication number: CN110117369B
Application number: CN201910405038.XA
Authority: CN
Inventors: 林权; 赵月; 刘厚; 赵玥琪; 杨喆; 杨柏
Original assignee: Jilin University
Current assignee: Jilin University
Priority date: 2019-05-16
Filing date: 2019-05-16
Publication date: 2022-03-01
Anticipated expiration: 2039-05-16
Also published as: CN110117369A

Abstract

An antibacterial adhesive conductive hydrogel and a preparation method and application thereof, belonging to the technical field of functional polymer materials. The invention adopts the method that the synthesized silver nano particles modified by polydopamine are compounded in the solution of conductive polymer monomers and polyvinyl alcohol, and initiator is utilized to initiate polymerization to prepare the conductive functional hydrogel in situ. The hydrogel has good biocompatibility, high biological adhesion, excellent conductive property, excellent antibacterial performance for gram-negative bacteria and gram-positive bacteria, and adjustable mechanical property. Can be used as a novel medical polymer wound dressing and has potential biological and medical application values in the aspects of promoting the healing of body wounds and the like.

Description

Antibacterial adhesive conductive hydrogel and preparation method and application thereof

Technical Field

The invention belongs to the technical field of high polymer materials, and particularly relates to an antibacterial adhesive conductive hydrogel, a preparation method and application thereof in wound dressings.

Background

The skin is the largest organ of the human body, and has the effects of protecting the human body from being damaged, preventing the invasion of microorganisms, maintaining the balance of body fluid and electrolytes and the like. Once the skin has serious defects, the wounds seriously affect the life and health of people. Wounds, especially extensive full thickness wounds, take a long time to repair, and acute and chronic wounds have been a major clinical problem. Therefore, the development of wound dressings with the characteristics of rapidly closing wounds, promoting wound healing, preventing bacterial growth and the like has important clinical value. To date, a variety of biomaterials including electrospun nanofibers, porous foams, polymeric membranes, functional hydrogels, and the like have been used in dressings for promoting wound healing. Among all biomaterials, hydrogel dressings have attracted attention because of their characteristics of maintaining a moist wound environment, absorbing tissue exudates, allowing oxygen to permeate and cool the wound surface, thereby alleviating pain of patients, and the like.

Although recently developed hydrogel-based wound dressings promote wound healing to some extent, these conventional hydrogels are easily absorbable by microorganisms and are easily infected by a large number of pathogenic bacteria parasitic on the surface of human skin, thereby causing inflammatory reactions, wound infections or immune reactions, which pose a direct threat to human health. In addition, skin is also an electrical signal sensitive tissue with 2.6mS/cm to 1X 10⁴Conductivity of mS/cm. Electroactive materials have been shown to be effective in promoting cell adhesion, proliferation, migration, and the like. Therefore, the development of the antibacterial adhesive conductive hydrogel can further promote wound healing, and has important significance clinically.

Disclosure of Invention

The invention aims to provide an antibacterial adhesive conductive hydrogel, a preparation method and application thereof in wound dressings.

Firstly, synthesizing poly-dopamine modified silver nanoparticles; and then adding a conductive polymer monomer and polyvinyl alcohol into the solution at 90 ℃, and initiating polymerization by using an initiator to form the dark green conductive hydrogel. The hydrogel has good biocompatibility, adhesiveness and antibacterial performance. By combining the excellent properties, the antibacterial adhesive electroactive hydrogel has potential biological and medical application values in the aspect of promoting wound healing in vivo as a novel medical polymer wound dressing.

The preparation method of the conductive hydrogel with antibacterial adhesion comprises the following specific steps:

(1) first, aqueous solutions of silver nitrate (0.1mM, 10-100 mL), sodium citrate (180mM, 1-10 mL), polyvinylpyrrolidone (4.2mM, 1-10 mL) and hydrogen peroxide (30 wt.%, 0.24-0.5 mL) were mixed and vigorously stirred open at room temperature. Then, sodium borohydride (100mm, 0.60-1.0 mL) is rapidly added into the mixed solution. After reacting for 30 minutes, a colloidal solution of silver nanoparticles was obtained.

(2) And dissolving the reactant 1 (47.5-285 mg) in the silver nanoparticle aqueous solution prepared above. And dropwise adding NaOH solution (1M), adjusting the pH value of the system to 8.5-11, and stirring the mixture at room temperature for 2 hours open and violently to obtain the silver nanoparticles coated by the reactant 1.

(3) And (3) preparing the antibacterial adhesive conductive hydrogel. And adding the reactant 2 (1-5 g) into the prepared silver nanoparticle solution (9-45 mL) coated with the reactant 1, and stirring at 90 ℃ until the silver nanoparticle solution is completely dissolved. Then, aniline (100-500. mu.L), 3-aminophenylboronic acid (75-375 mg) and reactant 3 (835-4175. mu.L, 6M) were added and stirred for 2 hours. After cooling to room temperature, adding reactant 4 solution (808-4040 mu L,6M) to form dark green conductive hydrogel with weak mechanical properties. Finally, the conductive hydrogel prepared above was cooled at-40 ℃ overnight. Finally, the antibacterial adhesive conductive hydrogel with widely adjustable mechanical properties is obtained.

In the above method, the silver nanoparticles may be triangular, spherical, etc.

In the above method, the reactant 1 may be tannic acid, dopamine, gallic acid, or the like.

In the above method, the reactant 2 may be polyvinyl alcohol, gelatin, agar, chitosan, cellulose, or the like.

In the above method, the reactant 3 may be hydrochloric acid, nitric acid, sulfuric acid.

In the above method, reactant 4 may be ammonium persulfate or potassium persulfate.

The invention has the following advantages: 1. the mechanical property of the prepared hydrogel can be changed by changing the content of the components, so that the mechanical property with large-range adjustability can be obtained. From low modulus to high modulus, the interface stability and environmental adaptability of the hydrogel in practical application are improved, and the application prospect of the hydrogel material in the aspect of biomedical materials is greatly expanded. 2. The prepared conductive hydrogel takes polyaniline and polymer with good biocompatibility as main raw materials, endows the hydrogel with good conductivity, and has the characteristics of no toxicity, low price, good biocompatibility and the like. 3. Different from traditional conductive hydrogel, the conductive hydrogel has obvious inhibition effect on gram negative (escherichia coli) and gram positive (staphylococcus aureus), namely, the hydrogel has broad-spectrum antibacterial activity. 4. The hydrogel has high water content, which can reach more than 90%. The electron microscope image after freeze-drying can prove that the hydrogel is loose and porous, and the structure is favorable for gas transportation, material exchange and the like. 5. Because the gel forming time of the hydrogel can be adjusted, the hydrogel has good processing property, and can be formed into various shapes by means of 3D printing, molding, injection and the like so as to meet the actual needs.

Drawings

FIG. 1: is a phase change diagram of the antibacterial conductive hydrogel prepared in example 1. As can be seen from the reagent bottle inclination experiment, the mixed solution of the prepared dopamine-coated silver nanoparticles, aniline, 3-aminophenylboronic acid and polyvinyl alcohol is in a sol state at room temperature, and becomes gel from the sol after ammonium persulfate is added.

FIG. 2: is an electron micrograph of the antibacterial conductive hydrogel prepared in example 1. As can be seen, the hydrogel was porous.

FIG. 3: the antibacterial effect of the antibacterial conductive hydrogel prepared in example 1 is shown. With the increase of silver nano particles in the hydrogel, the area of the antibacterial ring on the agar plate is larger and larger, which shows that the antibacterial effect of the conductive hydrogel is enhanced.

FIG. 4: the effect of the antimicrobial conductive hydrogel prepared for example 1 and a control on the treatment of diabetic foot wounds is shown. Compared with a control group, the antibacterial conductive hydrogel used as the wound dressing can effectively promote the healing of the diabetic foot wound and has faster wound healing rate.

Detailed Description

Example 1:

(1) solutions of silver nitrate (0.1mM, 97mL), sodium citrate (180mM, 1mL), polyvinylpyrrolidone (4.2mM,1mL) and hydrogen peroxide (30 wt.%, 0.24mL) were mixed and vigorously stirred at room temperature with an open mouth. Sodium borohydride (100mm, 0.30mL) was then added rapidly to the above mixed solution. After 30 minutes of reaction, a blue colloidal solution of silver nanoparticles having a triangular shape was obtained.

(2) 95mg of dopamine was dissolved in the silver nanoparticle aqueous solution prepared above. The dopamine-coated silver nanoparticles can be obtained by dropwise adding NaOH solution (1M), adjusting the pH value of the system to 8.5, and violently stirring the system for 2 hours at room temperature in an open manner.

(3) And (3) preparing the antibacterial adhesive conductive hydrogel. 9mL of the prepared dopamine-coated silver nanoparticle solution was added with 1g of polyvinyl alcohol, and stirred at 90 ℃ until completely dissolved. Then 200. mu.L of aniline, 75mg of 3-aminophenylboronic acid, and hydrochloric acid (1000. mu.L, 6M) were added and stirring was continued for 2 hours. After cooling to room temperature, a dark green, mechanically weak, electrically conductive hydrogel was formed after the addition of ammonium persulfate solution (808 μ L, 6M). Finally, the conductive hydrogel prepared above was cooled at-40 ℃ overnight. Finally, the antibacterial adhesive conductive hydrogel with widely adjustable mechanical properties is obtained.

Example 2:

(2) Tannic acid 95mg was dissolved in the silver nanoparticle aqueous solution prepared above. And dropwise adding NaOH solution (1M), adjusting the pH value of the system to 8.5, and violently stirring the mixture at room temperature for 2 hours in an open mode to obtain the silver nanoparticles coated with the tannic acid.

(3) And (3) preparing the antibacterial adhesive conductive hydrogel. 9mL of the tannic acid-coated silver nanoparticle solution prepared above was added with 1g of agar, and stirred at 90 ℃ until completely dissolved. Then 200. mu.L of aniline, 75mg of 3-aminophenylboronic acid, and sulfuric acid (1000. mu.L, 6M) were added and stirring was continued for 2 hours. After cooling to room temperature, a dark green, mechanically weak, electrically conductive hydrogel was formed after addition of potassium persulfate solution (808 μ L, 6M). Finally, the conductive hydrogel prepared above was cooled at-40 ℃ overnight. Finally, the antibacterial adhesive conductive hydrogel with widely adjustable mechanical properties is obtained.

Claims

1. A preparation method of antibacterial adhesive conductive hydrogel is characterized by comprising the following steps: the method comprises the following specific steps:

(1) firstly, mixing 10-100 mL of 0.1mM silver nitrate, 1-10 mL of 180mM sodium citrate, 1-10 mL of 4.2mM polyvinylpyrrolidone and 0.24-0.5 mL of 30 wt.% hydrogen peroxide aqueous solution, and then vigorously stirring the mixture at room temperature in an open manner; then, quickly adding 0.60-1.0 mL of 100mM sodium borohydride into the mixed solution; reacting for 30 minutes to obtain a colloidal solution of silver nanoparticles;

(2) dissolving 47.5-285 mg of reactant 1 in the prepared silver nanoparticle aqueous solution; dropwise adding 1M NaOH solution, adjusting the pH value of the system to 8.5-11, and stirring the mixture for 2 hours at room temperature to obtain silver nanoparticles coated with a reactant 1; the reactant 1 is tannic acid, dopamine or gallic acid;

(3) preparing the antibacterial adhesive conductive hydrogel; taking 9-45 mL of the prepared silver nanoparticle solution coated by the reactant 1, adding 1-5 g of the reactant 2, and stirring at 90 ℃ until the reactant is completely dissolved; then adding 100-500 mu L of aniline, 75-375 mg of 3-aminophenylboronic acid and 3835-4175 mu L of 6M reactant, and continuously stirring for 2 hours, wherein the reactant 3 is hydrochloric acid, nitric acid or sulfuric acid; cooling to room temperature, adding 808-4040 mu L of 6M reactant 4 solution to form dark green conductive hydrogel with weak mechanical properties, wherein the reactant 4 is ammonium persulfate or potassium persulfate; finally, cooling the prepared conductive hydrogel at-40 ℃ overnight; finally, the antibacterial adhesive conductive hydrogel with widely adjustable mechanical properties is obtained; the reactant 2 is polyvinyl alcohol, gelatin, agar, chitosan or cellulose.

2. The method for preparing the conductive hydrogel with antibacterial adhesion according to claim 1, wherein the method comprises the following steps: the silver nano particles in the step (1) are triangular or spherical.

3. The electrically conductive hydrogel produced by the method of any one of claims 1-2 for antimicrobial adhesive electrically conductive hydrogel.

4. Use of a conductive hydrogel according to claim 3 in the preparation of a wound dressing.