CN115068673B

CN115068673B - Preparation method and application of MXene-based self-catalyzed conductive hydrogel dressing

Info

Publication number: CN115068673B
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: 2023-06-06
Anticipated expiration: 2042-06-30
Also published as: CN115068673A

Abstract

The invention provides a preparation method and application of an MXene-based self-catalyzed 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, oxidation resistance, good conductivity, strong adhesiveness, strong mechanical strength and the like. The wound dressing is remarkable in repair of the infectious chronic wound under the assistance of electric stimulation, and can be used as a dressing of the infectious chronic wound surface. The strain sensor can be manufactured, and has application prospects in the aspects of wearable electronic equipment, electronic skin, personalized medical detection, human-computer interface, signal monitoring and the like.

Description

Preparation method and application of MXene-based self-catalyzed 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 self-catalyzed conductive hydrogel dressing and application of the dressing to repair of an infectious chronic wound under the assistance of electric stimulation.

Background

Bacterial infection is an important factor affecting wound healing. Serious bacterial infection often causes increased wound exudate, insufficient wound oxygenation, reduced nutrients and inhibition of granulation tissue formation, thereby preventing wound healing and enabling the wound to be chronically changed. In addition, excessive oxidative stress in damaged wounds also largely impedes the process of wound healing. Excessive reactive oxygen species (Reactive oxygen species, ROS) accumulate in the wound surface, which not only can cause strong inflammatory reaction and make the wound surface fragile, but also can inhibit the functions of endogenous stem cells and macrophages and prevent the regeneration of wound surface tissues. It is well known that ROS can significantly limit angiogenesis, leading to endothelial dysfunction, and that ROS produced by bacterial infection can cause significant damage to blood vessels and endothelial cells in addition to ROS produced by the wound itself, leading to the formation of chronic wounds. Traditional wound dressing (such as gauze, bandages, wound dressings and the like) do not have the 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 hydrogels, polymer films, nanofiber films, and the like, and endow the wound dressings with unique functions such as conductivity, oxidation resistance, and the like by compounding different materials and bioactive substances.

In recent years, conductive hydrogels have received attention because they can improve cell behavior at wounds, control cell and tissue growth by promoting cell proliferation, simulating electron or ion conductivity, pharmacological current, and the like, and promote wound healing. Besides the addition of common conductive polymer materials such as polypyrrole, polyaniline and metal nanowires in hydrogels, carbon-based materials are widely used due to their good biocompatibility and biological function. MXene is a two-dimensional material composed of transition metal carbides, and is highly interesting due to its high conductivity, hydrophilicity, chemical modifier, biocompatibility and biodegradability of the metalloids. Recently, MXene has also become a conductive nanofiller for polymer hydrogels, showing great potential in the soft electronics and biomedical fields.

Whereas appropriate Electrical Stimulation (ES) of tissues and cells can improve the biological functions of the heart, nerves, bones and muscles, researchers have begun focusing on the auxiliary effects of ES on wound healing. It has been reported that ES can affect cytokine expression by altering intrinsic current of wound surface, down-regulating Nuclear factor-kappa B (NF- κB) signal transduction, promote endothelial cell proliferation and migration, and accelerate blood circulation to promote wound healing and tissue regeneration. However, ES is not ideal as a stand alone treatment. Defective wounds are in a state of impaired signaling and ES cannot provide the antibacterial and anti-inflammatory environment required for wound repair, and therefore, it is necessary to develop a synergistic therapeutic strategy combining ES and other therapeutic approaches. The multifunctional conductive hydrogel and ES combined therapy can obviously promote collagen deposition, vascularization and epidermis remodeling on the basis of anti-inflammation and anti-infection, accelerate wound healing, and provide a new thought for the repair of chronic infection wound surfaces and the design of novel wound dressing.

Disclosure of Invention

The invention aims to provide a preparation method of an MXene-based self-catalyzed conductive hydrogel dressing and application of the dressing to repair of infectious chronic wounds under the assistance of electric stimulation.

Firstly, preparing Ag/TA@MXene nano sheets with a catalytic effect, then mixing acrylic acid with different volumes with water, adding a certain amount of gelatin solution, and uniformly stirring. Then, ammonium Persulfate (APS) as an initiator and N, N' -Methylene Bisacrylamide (MBA) as a crosslinking agent are sequentially added into the mixed solution, and finally, different amounts of Ag/TA@MXene solution are added while stirring, so that the conductive hydrogel can be prepared in a short time at room temperature through the catalysis of Ag/TA@Mxene on the APS under the conditions of no heating and no accelerator. The rich functional groups on the surface of the hydrogel endow the hydrogel with good adhesiveness, and the addition of Ag/TA@MXene not only has the characteristic of forming the hydrogel by autocatalysis, but also ensures that the hydrogel has excellent antibacterial property and oxidation resistance. In addition, the hydrogel has good biocompatibility and excellent electric conductivity and mechanical property. We have also further demonstrated the feasibility of the conductive hydrogels as dressings in combination with electrostimulation ES for use in the repair of infectious chronic wounds by cytotoxicity assays, animal assays, and the like. By combining the characteristics, the multifunctional self-catalytic conductive hydrogel has great potential as a novel wound dressing to further improve the healing efficiency of diabetic ulcers, pressure sores and other infectious chronic wounds, and provides a novel strategy for the design of the novel wound dressing and the clinical treatment of chronic infectious wounds.

The invention relates to a preparation method of Ag/TA@MXene nano-sheets and self-catalyzed multifunctional conductive hydrogel, which comprises the following specific steps:

(1) Preparation of Ag/TA@MXene nanosheets: taking 5mL of Ti with the concentration of 5mg/mL ₃ C ₂ The Tx nanoplatelet dispersion was placed in a 20mL glass reaction flask. 3-30mg of polyphenols are added, after stirring evenly, 200 mu L of Tris buffer is added, and the pH of the mixed solution is regulated to be approximately equal to 8.0. Then 30-90mg of silver nitrate is added, and the mixture is vigorously stirred for 2-4 hours at normal temperature, and then ultrasonic oscillation reaction is carried out for 10-20 minutes. And (3) washing the reacted solution with deionized water and centrifuging at 8800rpm for three times to obtain the Ag/TA@MXene nano sheet. It was lyophilized and stored at 4℃under nitrogen for further use.

(2) Preparation of multifunctional conductive hydrogel: adding 1.2mL of gelatin solution with concentration of 20% into 18mL of mixed solution with the mass ratio of the monomer to water 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 nano sheets while stirring, and standing for 30-60s to obtain the Ag/TA@MXene catalyzed conductive hydrogel dressing. A common hydrogel set without the addition of Ag/TA@MXene nanoplatelets is denoted 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 polyphenols may be tannic acid, tea polyphenols, and dextran polyphenols.

The invention has the following advantages: 1. the hydrogel has wide raw material sources, is easy to store, has good biocompatibility and is beneficial to commercialization of products; 2. the hydrogel dressing has simple and convenient preparation operation process, short time and no pollution. 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 without heating and without adding an accelerator. It has excellent antibacterial and antioxidant properties, and can prevent secondary infection of wound; 5. good conductivity of hydrogels can accelerate wound healing by promoting information communication between epidermal cells; 6. the scanning electron microscope image of the freeze-dried hydrogel shows that the hydrogel is of a loose porous structure, so that wound seepage can be absorbed conveniently; 7. the healing efficiency of the hydrogel dressing on the infectious chronic wound is further improved under the assistance of Electric Stimulation (ES); 8. the invention is suitable for dressing of different types of infection chronic wound surfaces, tissue regeneration auxiliary materials and the like, and has wide application prospect; 9. the conductive hydrogel can be made into a strain sensor, and has application prospects in the aspects of wearable electronic equipment, electronic skin, personalized medical detection, human-computer interface, signal monitoring and the like.

Drawings

Fig. 1: for the macroscopic solution and transmission electron microscopy of the Ag/TA@MXene nanoplatelets prepared in example 1, it can be seen that the Ag/TA@MXene nanoplatelet solution is brown-yellow in color, and the Ag nanoparticles formed in situ are relatively uniformly distributed on the surface of the MXene nanoplatelets.

Fig. 2: phase transition diagram of the multifunctional conductive hydrogel dressing prepared in example 1. By comparing the front-to-back changes of the substances in the inclined reagent bottles, we can see that after the Ag/TA@MXene nanoplatelets are added, the conductive hydrogel dressing can be rapidly formed at room temperature in a short time.

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

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

Fig. 5: an in vitro antibacterial experimental graph of the multifunctional hydrogel dressing prepared in the embodiment 1. By comparing the sizes of the antibacterial rings, the Ag/TA@MXene nano sheet can be seen to endow the conductive hydrogel with good antibacterial property, so that the hydrogel has good antibacterial effect.

Fig. 6: macroscopic images (panel a) and two-dimensional wound area measurements (panel B) of mice infected chronic wounds were repaired for different groups in embodiment 1. From the figure, the wound healing speed of mice in a control group and a common hydrogel group is slower after 12 days of wound treatment, and the wound healing speed of mice in a conductive hydrogel electricity-added stimulation group is fastest, so that the conductive hydrogel wound dressing prepared by us and the ES-assisted cooperative treatment method can further promote the healing of infectious chronic wounds.

Detailed Description

Example 1:

(1) Preparation of Ag/TA@MXene nanosheets: taking 5mL of 5mg/mLTi ₃ C ₂ The Tx nanoplatelet dispersion was placed in a 20mL glass reaction flask. 25mg of tannic acid was added, and after stirring uniformly, 200. Mu.L of Tris buffer was added to adjust the pH of the mixed solution to approximately 8.0. Then 90mg of silver nitrate is added, and the mixture is stirred vigorously at normal temperature for 4 hours, and then the reaction is carried out for 15 minutes by using ultrasonic oscillation. And (3) washing the reacted solution with deionized water and centrifuging at 8800rpm for three times to obtain the Ag/TA@MXene nano sheet. It was lyophilized and stored at 4℃under nitrogen for further use.

(2) Preparation of multifunctional conductive hydrogel: 1.2mL of gelatin solution with the concentration of 20% is added into 18mL of mixed solution with the mass ratio of acrylamide to water of 1:2, and the mixture is stirred uniformly. Then, 50mg APS,3.0mg MBA is added into the mixed solution in sequence, and finally 15mg of Ag/TA@MXene nano sheets are added while stirring, and the mixture is left for 40 seconds to obtain the Ag/TA@MXene catalyzed conductive hydrogel dressing.

Example 2:

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

(2) Preparation of multifunctional conductive hydrogel: 1.2mL of gelatin solution with concentration of 20% is added into 18mL of mixed solution with the mass ratio of acrylic acid to water of 1:2, and the mixture is stirred uniformly. Then, 50mg APS,3.0mg MBA is added into the mixed solution in sequence, and finally 15mg of Ag/TA@MXene nano sheets are added while stirring, and the mixture is left for 40 seconds to obtain the Ag/TA@MXene catalyzed conductive hydrogel dressing.

Example 3:

(1) Preparation of Ag/TA@MXene nanosheets: the concentration is 5mg/mL Ti ₃ C ₂ The Tx nanoplatelet dispersion was placed in a 20mL glass reaction flask. 25mg of tea polyphenol was added, and after stirring uniformly, 200. Mu.L of Tris buffer was added to adjust the pH of the mixed solution to approximately 8.0. Then 90mg of silver nitrate is added, and the mixture is stirred vigorously for 4 hours at normal temperature, and the reaction is carried out for 10 minutes by using ultrasonic oscillation. And (3) washing the reacted solution with deionized water and centrifuging at 8800rpm for three times to obtain the Ag/TA@MXene nano sheet. It was lyophilized and stored at 4℃under nitrogen for further use.

Claims

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

(1) Preparation of Ag/TA@MXene nanosheets: taking Ti with 5mL concentration of 5mg/mL ₃ C ₂ The Tx nano-sheet dispersion liquid is placed in a 20mL glass reaction bottle; adding 3-30mg polyphenols, stirring, adding 200 μl Tris buffer, and adjusting pH of the mixed solution to about 8.0; then adding 30-90mg of silver nitrate, vigorously stirring at normal temperature for 2-4h, and performing ultrasonic vibration reaction for 10-20 min; washing the reacted solution with deionized water and centrifuging at 8800rpm for three times to obtain Ag/TA@MXene nano sheets; freeze-drying, and storing at 4deg.C under nitrogen for use;

(2) Preparation of multifunctional conductive hydrogel: adding 1.2mL of gelatin solution with concentration of 20% into the 18mL mixed solution with the mass ratio of the monomer to water of 1:4-1:2, and uniformly stirring; then, sequentially adding 50-120-mg ammonium persulfate APS and 3.0-6.0mg N, N' -methylene bisacrylamide MBA into the mixed solution, adding 15-30mg Ag/TA@MXene nano sheets while stirring, and standing for 30-60s to obtain the Ag/TA@MXene catalyzed conductive hydrogel dressing.

2. The method for preparing the MXene-based self-catalyzed conductive hydrogel dressing according to claim 1, wherein the method comprises the following steps: the polyphenol substance in the step (1) is tannic acid or tea polyphenol or glucan polyphenol.

3. The method for preparing the MXene-based self-catalyzed conductive hydrogel dressing according to claim 1, wherein the method comprises the following steps: the monomer in the step (2) is acrylic acid or acrylamide or N-isopropyl acrylamide water-soluble polymerizable monomer.

4. The method for preparing the MXene-based self-catalyzed conductive hydrogel dressing according to claim 1, wherein the method comprises the following steps: hydrogels can be prepared at room temperature in a short time by the catalytic action of Ag/TA@Mxene without heating and without adding an accelerator.

5. A hydrogel prepared by the method for preparing an MXene-based autocatalytic conductive hydrogel dressing according to any one of claims 1-4, characterized in that: the hydrogel is of a loose porous structure, so that wound seepage can be absorbed conveniently; the hydrogel has good conductivity, and accelerates wound repair by promoting information communication among epidermal cells.

6. A hydrogel prepared by the method for preparing an MXene-based autocatalytic conductive hydrogel dressing according to any one of claims 1-4, characterized in that: the hydrogel is used for preparing a dressing for repairing an infectious chronic wound.

7. A hydrogel prepared by the method for preparing an MXene-based autocatalytic conductive hydrogel dressing according to any one of claims 1-4, characterized in that: the hydrogel is manufactured into a strain sensor, and a wireless technology is utilized to display signals on a mobile terminal of a mobile phone so as to realize motion detection.

8. A hydrogel prepared by the method for preparing an MXene-based autocatalytic conductive hydrogel dressing according to any one of claims 1-4, characterized in that: the hydrogel is used for preparing wearable electronic equipment or electronic skin.