CN115068673A

CN115068673A - Preparation method and application of MXene-based autocatalytic conductive hydrogel dressing

Info

Publication number: CN115068673A
Application number: CN202210771082.4A
Authority: CN
Inventors: 林权; 刘厚; 冯钰斌; 关琳; 杨欣婷
Original assignee: Jilin University
Current assignee: Jilin University
Priority date: 2022-06-30
Filing date: 2022-06-30
Publication date: 2022-09-20
Anticipated expiration: 2042-06-30
Also published as: CN115068673B

Abstract

The invention provides a preparation method and application of MXene-based autocatalytic conductive hydrogel dressing. The hydrogels of the present invention can be prepared rapidly at room temperature. The hydrogel has the characteristics of excellent antibacterial property and oxidation resistance, good conductivity, stronger adhesiveness, mechanical strength and the like. Under the assistance of electrical stimulation, the wound repair dressing has remarkable repair effect on the infected chronic wounds, and can be used as a dressing for the infected chronic wounds. The strain sensor can be manufactured, and has application prospects in wearable electronic equipment, electronic skin, personalized medical detection, human-computer interfaces, signal monitoring and other aspects.

Description

Preparation method and application of MXene-based autocatalytic conductive hydrogel dressing

Technical Field

The invention belongs to the technical field of high polymer materials, and particularly relates to a preparation method of an MXene-based autocatalytic conductive hydrogel dressing and application of the dressing to repairing of an infected chronic wound under the assistance of electrical stimulation.

Background

Bacterial infection is an important factor affecting wound healing. Severe bacterial infection often leads to increased wound exudate, insufficient oxygenation of the wound, reduced nutrients and inhibition of granulation tissue formation, thereby hindering wound healing and chronizing the wound. In addition, excessive oxidative stress in an injured wound also largely hinders the process of wound healing. Excessive Reactive Oxygen Species (ROS) are accumulated in the wound surface, so that not only can a strong inflammatory reaction be caused, but also the wound surface is fragile, and the functions of endogenous stem cells and macrophages can be inhibited, and the regeneration of wound surface tissues is hindered. It is well known that ROS can significantly limit angiogenesis, resulting in endothelial dysfunction, and that ROS produced by bacterial infections, in addition to ROS produced by the wound itself, can cause significant damage to blood vessels and endothelial cells, leading to the formation of chronic wounds. Traditional wound dressings (such as gauze, bandages, wound dressings and the like) do not have a biochemical function of promoting wound healing, so that the treatment effect on infectious wounds and some special chronic wounds (such as pressure sores, diabetic ulcers, bedsores and the like) is very limited. Therefore, researchers have developed various novel wound dressings such as hydrogel, polymer film, nanofiber film, etc., and have imparted unique functions such as conductivity and oxidation resistance to the above wound dressings by compounding various materials and bioactive substances.

In recent years, conductive hydrogels have attracted much attention because they can improve the cell behavior at wounds, and promote wound healing by controlling the growth of cells and tissues by means of promoting cell proliferation, simulating electronic or ionic conductivity, and pharmacologic current. Besides adding common conductive polymer materials such as polypyrrole, polyaniline and metal nanowires into hydrogel, carbon-based materials are widely applied due to good biocompatibility and biological function. MXene is a class of two-dimensional materials composed of transition metal carbides that have received a high degree of attention due to the high conductivity, hydrophilicity, chemical modification, biocompatibility, and biodegradability of its metalloids. Recently, MXene has also become a conductive nanofiller for polymer hydrogels, showing great potential in the field of soft electronics and biomedicine.

In view of the fact that appropriate Electrical Stimulation (ES) to tissues and cells can improve biological functions of the heart, nerves, bones and muscles, researchers have begun to focus on the auxiliary effects of ES on wound healing. ES reportedly can down-regulate Nuclear transcription factor (NF-kB) signal transduction by changing the inherent current of the wound surface, influence the expression of cytokines, promote the proliferation and migration of endothelial cells, and accelerate blood circulation to promote wound healing and tissue regeneration. However, ES as a separate treatment is not ideal. Defective wounds are in a state of impaired signal transmission and ES does not provide the antibacterial and anti-inflammatory environment required for wound repair, and therefore, there is a need to develop a synergistic therapeutic strategy combining ES and other therapeutic approaches. The combined treatment of the multifunctional conductive hydrogel and the ES can obviously promote collagen deposition, vascularization and epidermal remodeling on the basis of anti-inflammation and anti-infection, accelerate wound healing and provide a new idea for the repair of chronic infected wounds and the design of a novel wound dressing.

Disclosure of Invention

The invention aims to provide a preparation method of an MXene-based autocatalytic conductive hydrogel dressing and application of the dressing to repairing of an infected chronic wound under the assistance of electrical stimulation.

The method comprises the steps of firstly preparing Ag/TA @ MXene nanosheets with catalytic effects, then mixing acrylic acid and water in different volumes, adding a certain amount of gelatin solution, and stirring uniformly. And then, sequentially adding an initiator Ammonium Persulfate (APS) and a crosslinking agent N, N' -Methylene Bisacrylamide (MBA) into the mixed solution, finally adding Ag/TA @ MXene solutions with different amounts while stirring, and preparing the conductive hydrogel at room temperature in a short time under the catalysis of the Ag/TA @ Mxene on the APS under the conditions of no heating and no accelerator. The hydrogel has good adhesiveness due to abundant functional groups on the surface, and the addition of Ag/TA @ MXene not only has the characteristic of autocatalytic hydrogel formation, but also enables the hydrogel to have excellent antibacterial property and oxidation resistance. In addition, the hydrogel has good biocompatibility, and has excellent electric conductivity and mechanical properties. We also further demonstrate the feasibility of the conductive hydrogel as a dressing in combination with electrical stimulation ES for application in infectious chronic wound repair through cytotoxicity tests, animal tests, and the like. By combining the characteristics, the multifunctional autocatalytic conductive hydrogel has great potential as a novel wound dressing to further improve the healing efficiency of infected chronic wounds such as diabetic ulcer, pressure sore and the like, and provides a new strategy for the design of the novel wound dressing and the clinical treatment of the chronic infected wound.

The invention relates to a preparation method of Ag/TA @ MXene nanosheets and autocatalytic multifunctional conductive hydrogel, which comprises the following specific steps:

(1) preparation of Ag/TA @ MXene nanosheets: 5mL of Ti with a concentration of 5mg/mL is taken ₃ C ₂ The Tx nanosheet dispersion was placed in a 20mL glass reaction flask. Adding 3-30mg of polyphenol substances, stirring uniformly, adding 200 mu L of Tris buffer solution, and adjusting the pH value of the mixed solution to be approximately equal to 8.0. Then adding 30-90mg of silver nitrate, violently stirring for 2-4h at normal temperature, and carrying out ultrasonic oscillation reaction for 10-20 min. And (3) washing the reacted solution by using deionized water and repeatedly operating for three times by using 8800rpm for centrifugation to obtain the Ag/TA @ MXene nanosheet. It was lyophilized and stored at 4 ℃ under nitrogen for further use.

(2) Preparing multifunctional conductive hydrogel: adding 1.2mL of 20% gelatin solution into 18mL of mixed solution of the monomer and the water in a mass ratio of 1:4-1:2, and uniformly stirring. And then, sequentially adding 50-120mg of ammonium persulfate APS and 3.0-6.0mg of N, N' -methylene bisacrylamide MBA into the mixed solution, finally adding 15-30mg of Ag/TA @ MXene nanosheets while stirring, and standing for 30-60s to obtain the Ag/TA @ MXene catalyzed conductive hydrogel dressing. A common hydrogel set without Ag/TA @ MXene nanoplatelets is represented by PAA.

In the above method, the monomer may be a water-soluble polymerizable monomer such as acrylic acid, acrylamide and N-isopropylacrylamide.

In the above method, the polyphenol can be tannic acid, tea polyphenol, and grape polyphenol.

The invention has the following advantages: 1. the hydrogel has wide raw material source, easy storage and good biocompatibility, and is beneficial to commercialization of products; 2. the hydrogel dressing is simple and convenient in preparation and operation process, short in time, green and pollution-free. 3. The hydrogel dressing has strong adhesiveness and certain mechanical strength, is convenient to fix and replace, and can avoid secondary damage caused by external force; 4. the conductive hydrogel can be prepared at room temperature in a short time by the catalytic action of Ag/TA @ Mxene on APS under the conditions of no heating and no accelerator. It has excellent antibacterial and antioxidant effects, and can prevent secondary infection of wound; 5. the good conductivity of the hydrogel can accelerate wound healing by promoting information communication among epidermal cells; 6. the scanning electron microscope image of the hydrogel after freeze-drying shows that the hydrogel is of a loose porous structure and is convenient for absorbing wound exudate; 7. the hydrogel dressing is assisted by Electric Stimulation (ES), so that the healing efficiency of the infected chronic wound is further improved; 8. the invention is suitable for dressings, tissue regeneration auxiliary materials and the like of different types of infectious chronic wounds, and has wide application prospect; 9. the conductive hydrogel can be made into a strain sensor, and has application prospects in wearable electronic equipment, electronic skin, personalized medical detection, human-computer interfaces, signal monitoring and other aspects.

Drawings

FIG. 1: in the macroscopic solution and transmission electron microscope images of the Ag/TA @ MXene nanosheet prepared in example 1, it can be seen that the color of the Ag/TA @ MXene nanosheet solution is brown yellow, and Ag nanoparticles formed in situ are uniformly distributed on the surface of the MXene nanosheet.

FIG. 2: phase transition diagram of the multifunctional conductive hydrogel dressing prepared for example 1. By comparing the front and back changes of the substances in the inclined reagent bottle, the conductive hydrogel dressing can be quickly formed at room temperature in a short time after the Ag/TA @ MXene nanosheets are added.

FIG. 3: scanning electron microscope images of the multifunctional conductive hydrogel dressing prepared for example 1 after freeze-drying. From the figure, we can clearly see that the loose and porous structure in the hydrogel is beneficial to absorption of seepage and material exchange.

FIG. 4: conductivity histogram of hydrogel prepared for embodiment 1. As shown in the figure, the conductivity of the hydrogel after the Ag/TA @ MXene nanosheets are added is obviously improved, and the conductivity is improved along with the increase of the content of the Ag/TA @ MXene nanosheets in the hydrogel.

FIG. 5: in vitro antibacterial experimental graph of the multifunctional hydrogel dressing prepared for embodiment 1. By comparing the size of the antibacterial ring, the Ag/TA @ MXene nanosheets endow the conductive hydrogel with good antibacterial property, and the hydrogel has a good antibacterial effect.

FIG. 6: macroscopic view (panel a) and two-dimensional wound area measurement (panel B) of infected chronic wounds for different groups of mice in example 1 were repaired. From the figure, we can see that after 12 days of wound treatment, the wound healing speed of mice in the control group and the common hydrogel group is slower, and the wound healing speed of mice in the conductive hydrogel electrically stimulated group is fastest, which shows that the prepared conductive hydrogel wound dressing and the ES-assisted synergistic treatment method can further promote the healing of the infected chronic wound.

Detailed Description

Example 1:

(1) preparation of Ag/TA @ MXene nanosheets: 5mL of 5mg/mL Ti was taken ₃ C ₂ The Tx nanosheet dispersion was placed in a 20mL glass reaction flask. 25mg of tannic acid is added, and after uniform stirring, 200. mu.L of Tris buffer is added to adjust the pH of the mixed solution to be approximately equal to 8.0. Then 90mg of silver nitrate is added, the mixture is stirred vigorously for 4 hours at normal temperature, and ultrasonic oscillation is used for reaction for 15 min. And (3) washing the reacted solution by using deionized water and repeatedly operating for three times by using 8800rpm for centrifugation to obtain the Ag/TA @ MXene nanosheet. Freeze-drying at 4 deg.C under nitrogenAnd storing for later use.

(2) Preparing multifunctional conductive hydrogel: adding 1.2mL of 20% gelatin solution into 18mL of mixed solution of acrylamide and water at a mass ratio of 1:2, and uniformly stirring. And then sequentially adding 50mg of APS and 3.0mg of MBA into the mixed solution, finally adding 15mg of Ag/TA @ MXene nanosheet while stirring, and standing for 40 seconds to obtain the Ag/TA @ MXene catalyzed conductive hydrogel dressing.

Example 2:

(1) preparation of Ag/TA @ MXene nanosheets: 5mL of Ti with a concentration of 5mg/mL is taken ₃ C ₂ The Tx nanosheet dispersion was placed in a 20mL glass reaction flask. 25mg of tannic acid is added, and after uniform stirring, 200. mu.L of Tris buffer is added to adjust the pH of the mixed solution to be approximately equal to 8.0. Then 90mg of silver nitrate is added, the mixture is stirred vigorously for 4 hours at normal temperature, and ultrasonic oscillation is used for reaction for 20 minutes. And (3) washing the reacted solution by using deionized water and repeatedly operating for three times by using 8800rpm for centrifugation to obtain the Ag/TA @ MXene nanosheet. It was lyophilized and stored at 4 ℃ under nitrogen for further use.

(2) Preparing multifunctional conductive hydrogel: adding 1.2mL of 20% gelatin solution into 18mL of mixed solution of acrylic acid and water at a mass ratio of 1:2, and uniformly stirring. And then, sequentially adding 50mg of APS and 3.0mg of MBA into the mixed solution, finally adding 15mg of Ag/TA @ MXene nanosheets while stirring, and standing for 40 seconds to obtain the Ag/TA @ MXene catalyzed conductive hydrogel dressing.

Example 3:

(1) preparation of Ag/TA @ MXene nanosheets: ti concentration of 5mg/mL ₃ C ₂ The Tx nanosheet dispersion was placed in a 20mL glass reaction flask. Adding 25mg of tea polyphenol, stirring uniformly, adding 200 mu L of Tris buffer solution, and adjusting the pH value of the mixed solution to be approximately equal to 8.0. Then 90mg of silver nitrate is added, the mixture is stirred vigorously for 4 hours at normal temperature, and ultrasonic oscillation is used for reaction for 10 minutes. And (3) washing the reacted solution by using deionized water and repeatedly operating for three times by using 8800rpm for centrifugation to obtain the Ag/TA @ MXene nanosheet. It was lyophilized and stored at 4 ℃ under nitrogen for further use.

Claims

1. A preparation method of MXene-based autocatalytic conductive hydrogel dressing is characterized by comprising the following steps: the method comprises the following specific steps:

(1) preparation of Ag/TA @ MXene nanosheets: 5mL of Ti with a concentration of 5mg/mL is taken ₃ C ₂ Placing the Tx nanosheet dispersion in a 20mL glass reaction bottle; adding 3-30mg of polyphenol substances, stirring uniformly, adding 200 mu L of Tris buffer solution, and adjusting the pH value of the mixed solution to be approximately equal to 8.0; then adding 30-90mg of silver nitrate, violently stirring for 2-4h at normal temperature, and carrying out ultrasonic oscillation reaction for 10-20 min; washing the reacted solution by deionized water and repeatedly operating for three times by means of 8800rpm centrifugation to obtain Ag/TA @ MXene nanosheets; freeze-drying, and storing at 4 deg.C under nitrogen;

(2) preparing multifunctional conductive hydrogel: adding 1.2mL of 20% gelatin solution into 18mL of mixed solution of the monomers and the water in a mass ratio of 1:4-1:2, and uniformly stirring; then, sequentially adding 50-120mg of ammonium persulfate APS and 3.0-6.0mg of N, N' -methylene bisacrylamide MBA into the mixed solution, finally adding 15-30mg of Ag/TA @ MXene nanosheets while stirring, and standing for 30-60s to obtain the Ag/TA @ MXene catalyzed conductive hydrogel dressing; a common hydrogel set without Ag/TA @ MXene nanoplatelets is represented by PAA.

2. The method for preparing an MXene-based autocatalytic conductive hydrogel dressing as claimed in claim 1, wherein: the polyphenols in step (1) can be tannic acid, tea polyphenols and grape polyphenols.

3. The method for preparing an MXene-based autocatalytic conductive hydrogel dressing as claimed in claim 1, wherein: the monomer in step (2) may be a water-soluble polymerizable monomer such as acrylic acid, acrylamide and N-isopropylacrylamide.

4. The method for preparing an MXene-based autocatalytic conductive hydrogel dressing as claimed in claim 1, wherein: under the conditions of no heating and no accelerator addition, the hydrogel can be prepared at room temperature in a short time through the catalytic action of Ag/TA @ Mxene; the hydrogel has the characteristics of excellent antibacterial property and oxidation resistance, stronger adhesiveness, mechanical strength and the like.

5. A hydrogel prepared by a method for preparing an MXene-based autocatalytic conducting hydrogel dressing as claimed in any one of claims 1 to 4 characterized in that: the hydrogel is a loose porous structure, so that wound exudate can be absorbed conveniently; the hydrogel has the characteristics of good conductivity, acceleration of wound repair through promotion of information communication between epidermal cells and the like.

6. The hydrogel prepared by the preparation method of any MXene-based autocatalytic conductive hydrogel dressing as claimed in claims 1-4, characterized in that: the hydrogel is used as a dressing, has obvious repair effect on the infected chronic wounds with the assistance of Electrical Stimulation (ES), and can be used as a dressing of the infected chronic wounds and a tissue regeneration auxiliary material.

7. The hydrogel prepared by the preparation method of any MXene-based autocatalytic conductive hydrogel dressing as claimed in claims 1-4, characterized in that: the hydrogel can be made into a strain sensor, and signals are displayed on a mobile terminal of a mobile phone by utilizing a wireless technology, so that motion detection is realized; the method has application prospects in wearable electronic equipment, electronic skin, personalized medical detection, human-computer interfaces, signal monitoring and other aspects.