A piezoelectric hydrogel material for wound repair and preparation method thereof

Abstract

The present invention belongs to the technical field of wound repair materials, specifically relating to a piezoelectric hydrogel material for wound repair and its preparation method. The carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel disclosed in the present invention can effectively inhibit bacterial proliferation under ultrasonic stimulation, exerting an antibacterial effect. The hydrogel has a porous structure, good swelling properties, and the ability to promote wound healing. The hydrogel material of the present invention has good adhesion, is safe and non-toxic, is easy to use, and has a simple and easy preparation method. It is a material that can effectively promote the repair of skin wounds and is suitable for use in fields such as wound repair.

Description

Technical Field

[0001] The present invention relates to the technical field of wound repair materials, and in particular to a piezoelectric hydrogel material for wound repair and a preparation method thereof. Background Art

[0002] As the first line of defense between the human body and the outside world, the skin is extremely vulnerable to damage from the external environment. The skin not only maintains internal stability and prevents water and electrolyte loss, but also forms an effective barrier between the body and the external environment, defending against pathogens and preventing infection. Wound healing after skin injury is a complex process consisting of three main phases: inflammation, proliferation, and remodeling.

[0003] Chronic wounds caused by bacterial infections present a serious challenge, especially skin wound infections caused by Staphylococcus aureus, which often lead to slow wound healing and severe tissue damage, even organ damage and death. Therefore, clearing bacteria from the wound site is an important measure to promote wound healing. Clinically, wound infections are mainly treated by taking or injecting antibiotics for antibacterial purposes, but such local drug concentrations may not reach the effective antibacterial range and cause allergic reactions, and may also cause bacteria to develop drug resistance. Therefore, materials / dressings that act directly on wounds and are safe to use are receiving increasing attention.

[0004] By using antibacterial dressings, bacteria can be effectively killed without causing damage to other tissues. The main goal of wound dressings is to protect wounds from bacterial infection and promote wound healing. Hydrogels have good mechanical properties, good carrier properties, excellent biocompatibility, and the ability to provide a moist environment for wound repair. Therefore, they are considered to be ideal dressing materials that promote wound healing and have received widespread attention. Hydrogels can promote wound healing by exerting antibacterial, anti-inflammatory, and cell differentiation and proliferation promoting functions by locally releasing bioactive substances in the wound.

[0005] Carboxymethyl chitosan (CMCS) is a water-soluble chitosan derivative that retains chitosan's inherent biological functions while also exhibiting excellent water absorption and retention properties. Furthermore, the carboxymethyl group is a reactive group that readily reacts with other chemicals, introducing new functionalities into the material. Carbomer (CBM), a synthetic polymer, offers advantages such as high viscosity, excellent thermal stability, and good tissue compatibility, making it a high-quality drug carrier and hydrogel matrix. Tannic acid possesses excellent antioxidant, antibacterial, and antitumor properties. Due to its phenolic hydroxyl groups, tannic acid can form non-covalent interactions with other polymers. Tannic acid also exhibits antibacterial and hemostatic properties. Clinical limitations of hydrogels based on carboxymethyl chitosan are limited hemostatic function and poor antibacterial properties. Tannic acid can act as a crosslinker with carboxymethyl chitosan, enhancing its hemostatic and antibacterial properties while also stimulating angiogenesis and collagen deposition. FeWO4 nanomaterials can be synthesized by a simple hydrothermal method, their shape can be controlled by pH, and they have high piezoelectric catalytic efficiency. Therefore, designing a new carboxymethyl chitosan-carbomer-tannic acid / FeWO4 antibacterial composite hydrogel that promotes wound healing could provide new ideas and methods for the development of wound dressings. Summary of the Invention

[0006] The purpose of the present invention is to provide a piezoelectric hydrogel material for wound repair and a preparation method thereof, so as to solve the deficiencies of the prior art.

[0007] The present invention adopts the following technical solutions:

[0008] A piezoelectric hydrogel material for wound repair and a preparation method thereof, the method comprising the following steps:

[0009] Step 1, dissolving Carbomer 940 in water at a certain temperature, and then adding carboxymethyl chitosan, tannic acid and FeWO4 nanomaterials;

[0010] Step 2: Add a pH regulator to adjust the pH of the solution, and mix evenly to obtain a piezoelectric hydrogel.

[0011] In the above technical solution, further,

[0012] The dissolving temperature is 45-55°C.

[0013] The concentration of carbomer 940 is 1-2%, the concentration of carboxymethyl chitosan is 1-2%, the concentration of tannic acid is 1-2%, and the concentration of FeWO4 is 2-4 mg / mL.

[0014] The amount of Carbomer 940 added is 10-15 mL, the amount of carboxymethyl chitosan added is 2-4 mL, the amount of tannic acid added is 2-4 mL, and the amount of FeWO4 added is 1-2 mL.

[0015] The FeWO4 is a FeWO4 nanorod with piezoelectric effect. The preparation method is as follows: 1-3 mmol (NH4)2Fe(SO4)2·6H2O and 1-3 mmol Na2WO4·2H2O are respectively dissolved in 5-10 mL ultrapure water; the dissolved Na2WO4·2H2O is added dropwise to the (NH4)2Fe(SO4)2·6H2O solution and stirred continuously; then 10-20 mL ultrapure water is added and stirred for 30-60 minutes; the pH is adjusted to 9-9.5 with 3-5 M sodium hydroxide, the reaction is carried out at 160-180° C. for 24-36 hours, and the FeWO4 nanorods are obtained after washing with water and ethanol.

[0016] The pH regulator is sodium hydroxide or triethanolamine, which is used to adjust the pH to 6-7.

[0017] The present invention also provides the use of the carbomer-carboxymethyl chitosan-tannic acid / FeWO4 piezoelectric hydrogel obtained by the above preparation method in skin wound repair.

[0018] Beneficial effects of the present invention:

[0019] The FeWO4 added to the present invention is a piezoelectric material with a piezoelectric effect. It generates ROS under ultrasonic stimulation, exerting an antibacterial effect. The carbomer-carboxymethyl chitosan-tannic acid / FeWO4 piezoelectric hydrogel prepared by the present invention has a porous structure, good swelling properties, and promotes wound healing. The hydrogel material of the present invention has good adhesion, is safe and non-toxic, and has a simple and easy preparation method. It is a material that can effectively promote the repair of skin wounds and is suitable for wound repair and other fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a picture of carbomer-carboxymethyl chitosan-tannic acid / FeWO4 piezoelectric hydrogel.

[0021] Figure 2 This is a scanning electron micrograph of carbomer-carboxymethyl chitosan-tannic acid / FeWO4 piezoelectric hydrogel.

[0022] Figure 3 It is a graph of in vitro antibacterial activity.

[0023] Figure 4 It is a graph of antimicrobial activity in vivo.

[0024] Figure 5 It is a graph of the wound healing area.

[0025] Figure 6 This is an H&E staining image. DETAILED DESCRIPTION

[0026] The present invention will be further explained below in conjunction with the examples and drawings. The following examples are only used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0027] Example 1: A piezoelectric hydrogel material for wound repair and its preparation method

[0028] (1) Preparation of FeWO4 nanorods

[0029] Dissolve 3 mmol of (NH₄)₂Fe(SO₄)₂·6H₂O and 3 mmol of Na₂WO₄·2H₂O in 5 mL of ultrapure water. Add the dissolved Na₂WO₄·2H₂O dropwise to the (NH₄)₂Fe(SO₄)₂·6H₂O solution with continuous stirring. Then, add 20 mL of ultrapure water and stir for 30 minutes. Adjust the pH to 9 with 5 M sodium hydroxide, react at 160°C for 24 hours, and wash with water and ethanol to obtain FeWO₄ nanorods.

[0030] (2) Preparation of piezoelectric hydrogel

[0031] Carbomer 940 was dissolved at 50°C to prepare a 2% (w / t) solution. 10 mL of the 2% Carbomer 940 solution was mixed with 4 mL of carboxymethyl chitosan, 4 mL of tannic acid, and 2 mL of 4 mg / mL FeWO4 nanorods. Triethanolamine was added to adjust the pH to 7.0 to obtain a piezoelectric hydrogel.

[0032] Example 2: Antibacterial activity detection

[0033] (1) In vitro antibacterial activity detection

[0034] 100 μL (10 8 CFU / mL) Staphylococcus aureus suspension was inoculated on an agar plate, and then 100 μL of carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel was added to the culture medium and ultrasonic (1.0 MHz, 1 W·cm -1 After stimulation with 5% CO2 (5 min, 50% duty cycle), the cells were cultured in a shaker at 37°C at a speed of 150 r / min for 0.5 h and 4 h, respectively, and the total number of colonies was calculated.

[0035] The results are as follows Figure 3 As shown in the figure, after adding carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel and ultrasonic stimulation, the total colony count was significantly reduced, and it had good in vitro antibacterial activity.

[0036] (2) In vivo antibacterial activity detection

[0037] Male Kunming mice weighing 22-25g and aged 5-6 weeks were selected and randomly divided into the control group, US group, CBM-CMCS-TA group, CBM-CMCS-TA / FeWO4 group, and CBM-CMCS-TA / FeWO4+US group. All mice were anesthetized with isoflurane, and after shaving the back, a 9mm full-thickness circular wound was created on the back of the mice using an 8mm punch. 50μL of Staphylococcus aureus (10 8 CFU / mL) was applied to the wound surface to establish a bacterial infection model. 50 μL PBS (0.01 M, pH 7.4) was added to the control group, and ultrasonic treatment (1.0 MHz, 1 W·cm -1 , 5 min, 50% duty cycle), 50 μL carbomer-carboxymethyl chitosan-tannic acid hydrogel was added to the CBM-CMCS-TA group, carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel was added to the CBM-CMCS-TA / FeWO4 group, and carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel was added to the CBM-CMCS-TA / FeWO4+US group and ultrasonic treatment (1.0 MHz, 1 W·cm -1 After all operations were completed, the skin tissue was collected, crushed, and dispersed in 5 mL of PBS. The tissue sample containing PBS was then diluted and cultured on an agar plate to count the total number of colonies.

[0038] The results are as follows Figure 4 As shown in the figure, after adding carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel and ultrasonic stimulation, the total bacterial count was significantly reduced, and it had good in vivo antibacterial activity.

[0039] Example 3: Wound healing promotion performance test

[0040] Male Kunming mice weighing 22-25 g and aged 5-6 weeks were selected and randomly divided into the control group, US group, CBM-CMCS-TA group, CBM-CMCS-TA / FeWO4 group, and CBM-CMCS-TA / FeWO4+US group. All mice were anesthetized with isoflurane, and after shaving the back, a 9 mm full-thickness circular wound was created on the back of the mice using an 8 mm punch. 10 μL of Staphylococcus aureus (10 8 CFU / mL) was applied to the wound surface to establish a bacterial infection model. 50 μL PBS (0.01 M, pH 7.4) was added to the control group, and ultrasonic treatment (1.0 MHz, 1 W·cm -1, 5 min, 50% duty cycle), 50 μL carbomer-carboxymethyl chitosan-tannic acid hydrogel was added to the CBM-CMCS-TA group, carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel was added to the CBM-CMCS-TA / FeWO4 group, and carbomer-carboxymethyl chitosan-tannic acid / FeWO4 hydrogel was added to the CBM-CMCS-TA / FeWO4+US group and ultrasonic treatment (1.0 MHz, 1 W·cm -1 , 5 min, 50% duty cycle). Wound changes were recorded by photographing, and skin tissue samples were taken on days 7 and 14 after treatment for hematoxylin-eosin (H&E) staining to evaluate wound healing effects.

[0041] like Figure 5 As shown in the figure, the wound healing efficiency of the CBM-CMCS-TA / FeWO4+US group was significantly higher than that of the other groups, and the wound area was significantly smaller than that of the control group. After 14 days of treatment, the wounds of the mice in the CBM-CMCS-TA / FeWO4+US group were basically healed. This shows that the CBM-CMCS-TA / FeWO4 piezoelectric hydrogel prepared by the present invention can accelerate wound healing. Figure 6 As can be seen, the CBM-CMCS-TA / FeWO4+US group showed significant epidermal growth. On the 7th day after surgery, the wound surface was covered by epidermal tissue, and the scab began to separate from the epidermis. Simultaneously, the stratum corneum appeared, indicating that the wound surface had completely healed. The stratum corneum continued to form on the 14th day. This demonstrates that the hydrogel prepared by this invention can accelerate the repair of damaged tissue and promote epidermalization.

[0042] The embodiments described above provide a detailed description of the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. It should be pointed out that for ordinary technicians in this technical field, various changes and modifications can be made without departing from the spirit and scope of the present invention. These changes and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a piezoelectric hydrogel for wound repair, characterized in that: The hydrogel is formed by cross-linking carbomer 940, carboxymethyl chitosan, tannic acid and FeWO4, and the preparation method thereof comprises the following steps: Step 1, dissolving carbomer 940 in water at a certain temperature, and then adding carboxymethyl chitosan, tannic acid and FeWO4 nanomaterials; the dissolution temperature of carbomer 940 is 45-55 ° C; FeWO4 is FeWO4 nanorods with piezoelectric effect, and the preparation method is as follows: dissolving 1-3 mmol (NH4)2Fe(SO4)2∙6H2O and 1-3 mmol Na2WO4·2H2O in 5-10 mL ultrapure water respectively; adding the dissolved Na2WO4·2H2O dropwise to the (NH4)2Fe(SO4)2∙6H2O solution while stirring continuously; then adding 10-20 mL ultrapure water and stirring for 30-60 min; adjusting the pH to 9-9.5 with 3-5 M sodium hydroxide, reacting at 160-180 ° C for 24-36 h, and washing with water and ethanol to obtain FeWO4 nanorods; Step 2: Add a pH regulator to adjust the pH of the solution, and mix evenly to obtain a piezoelectric hydrogel.

2. The method for preparing a piezoelectric hydrogel for wound repair according to claim 1, characterized in that: In step 1, the concentration of carbomer 940 is 1-2%, the concentration of carboxymethyl chitosan is 1-2%, the concentration of tannic acid is 1-2%, and the concentration of FeWO4 is 1-2 mg / mL.

3. The method for preparing a piezoelectric hydrogel for wound repair according to claim 1, characterized in that: In step 1, the amount of carbomer 940 added is 10-15 mL, the amount of carboxymethyl chitosan added is 2-4 mL, the amount of tannic acid added is 2-4 mL, and the amount of FeWO4 added is 1-2 mL.

4. The method for preparing a piezoelectric hydrogel for wound repair according to claim 1, characterized in that: The pH regulator in step 2 is sodium hydroxide or triethanolamine, and the pH is adjusted to 6-7.

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