Antibacterial and antioxidant ultrasonic induced piezoelectric hydrogel as well as preparation method and application thereof

Abstract

The invention provides antibacterial and antioxidant ultrasonic-induced piezoelectric hydrogel and a preparation method and application thereof.According to the antibacterial and antioxidant ultrasonic-induced piezoelectric hydrogel, a compound containing amido and double bonds reacts with a halogenated hydrocarbon compound through quaternization reaction to synthesize a series of cationic quaternary ammonium salt serving as an antibacterial component, and an antioxidant component is introduced; and adding the hydrogel into a hydrogel precursor solution containing acrylic acid and N-isopropylacrylamide, and synthesizing the ionized water gel with antibacterial, antioxidant and ultrasonic induced piezoelectric properties by adopting a photocuring strategy. The hydrogel shows excellent mechanical properties, good biocompatibility and adhesion, and can generate an endogenous electric field under ultrasonic excitation to regulate cell behaviors. Experimental results show that the hydrogel can effectively promote infection inhibition and alleviate oxidative stress, and has a remarkable treatment effect in diabetes infected wound and articular cartilage repair. The hydrogel is simple in preparation method, low in cost and suitable for the biomedical fields of wound treatment, tissue repair and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of surgical biomedical materials, and more particularly to an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel, and a preparation method and application thereof. Background Art

[0002] Tissue damage is one of the major challenges facing clinical medicine. Its causes mainly come from traffic accidents, mechanical accidents, chronic diseases, and postoperative infections. Tissue repair is a complex biological process involving multiple links such as inflammatory response, cell proliferation and migration, tissue regeneration and remodeling. However, the wound surface is often accompanied by adverse factors such as bacterial infection and oxidative stress, which causes the wound to be in a chronic inflammatory state for a long time. Excessive accumulation of reactive oxygen species (ROS) can induce high oxidative stress, disrupt cell metabolism, and hinder the normal healing process. At the same time, oxidative stress damage also increases the risk of bacterial infection, further exacerbating ROS levels and forming a vicious cycle. Once the wound develops into an infected wound, the disorder of the local microenvironment and the interruption of the healing cascade will significantly delay the healing process. Therefore, developing a therapeutic strategy that can effectively promote tissue repair and prevent complications has become a difficult problem that needs to be solved urgently in clinical medicine.

[0003] Hydrogels are widely used in wound dressings, tissue engineering, and drug delivery due to their excellent biocompatibility, softness, and high hydration properties. Their unique physical properties can mimic biological tissues, providing a moist healing environment for wounds, thereby accelerating healing and alleviating pain. Currently, researchers have developed a variety of multifunctional hydrogels by introducing antibiotics, metal nanomaterials, antioxidants, and anti-inflammatory drugs, aiming to eliminate bacterial infections and reduce inflammatory responses. However, these methods have obvious limitations: the use of antibiotics may cause drug resistance problems, metal nanomaterials may produce cytotoxicity, and antioxidants and anti-inflammatory drugs have poor biocompatibility. In addition, existing hydrogels are difficult to deeply regulate the internal mechanisms of cells and cannot effectively promote cell proliferation and tissue remodeling, which limits their application in tissue repair.

[0004] In recent years, electrical stimulation therapy has garnered widespread attention due to its ability to mimic endogenous charge-mediated healing mechanisms. By modulating cell behavior, electrical stimulation can significantly promote wound healing. Against this backdrop, ultrasound-induced piezoelectric hydrogels, as a novel stimuli-responsive material, have shown great potential for application. Piezoelectric hydrogels can generate a piezoelectric effect through ultrasound activation, thereby regulating cell proliferation, migration, and differentiation, accelerating tissue repair. However, most existing piezoelectric hydrogels rely on the incorporation of fillers such as inorganic piezoelectric ceramics or piezoelectric polymers to achieve piezoelectric properties. These fillers often suffer from issues such as easy aggregation, poor flexibility, and insufficient biocompatibility, severely limiting their application in tissue repair. Furthermore, current research is still in its early stages, and most ultrasound-induced hydrogels lack the ability to simultaneously possess multiple functions—antibacterial, antioxidant, and cell behavior regulation—making them inadequate for the comprehensive needs of tissue repair. Therefore, developing a multifunctional hydrogel with combined antibacterial, antioxidant, and piezoelectric properties would not only effectively combat bacterial infection and oxidative stress, but also promote tissue repair by modulating cell behavior, potentially offering significant clinical applications. The research and development of this new hydrogel will promote the further development of piezoelectric hydrogel in the biomedical field and provide an innovative solution for tissue repair. Summary of the Invention

[0005] The purpose of the present invention is to overcome the deficiencies in the prior art and provide a preparation method and application of an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides a method for preparing an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel, comprising the following steps:

[0008] (1) through a quaternization reaction, a compound containing an amine group and a double bond is reacted with a halogenated hydrocarbon compound to synthesize a cationic quaternary ammonium salt;

[0009] (2) uniformly mixing the cationic quaternary ammonium salt, antioxidant component, acrylic acid, N-isopropylacrylamide, crosslinking agent and photoinitiator obtained in step (1) to obtain a hydrogel precursor solution;

[0010] (3) The hydrogel precursor solution in step (2) is solidified by a photocuring process to obtain an ionic hydrogel with antibacterial and antioxidant properties, wherein the hydrogel can generate a piezoelectric ion effect under ultrasound induction.

[0011] In this technical solution, a one-pot in-situ photocuring strategy is used to integrate the properties of cationic quaternary ammonium salts and antioxidant components into a single hydrogel system with piezoelectric properties that can be induced by ultrasound. A multifunctional hydrogel with antibacterial, antioxidant and ultrasound-induced piezoelectric properties is successfully prepared without the need for complex post-modification. The photocuring technology has the advantages of rapid prototyping, low energy consumption, and no solvent residue, making it suitable for large-scale production. Specifically, a cationic quaternary ammonium salt is synthesized as an antibacterial component through a quaternization reaction, thereby giving the hydrogel a positively charged surface, achieving broad-spectrum physical antibacterial properties through electrostatic action, effectively preventing bacterial infection, while avoiding the problem of drug resistance without relying on antibiotics. Furthermore, by introducing antioxidant components, the hydrogel can scavenge free radicals, inhibit oxidative stress, reduce inflammatory responses, and accelerate wound healing. Furthermore, the piezoelectric properties induced by ultrasound enable the hydrogel to generate electrical signals, directly regulating cell proliferation, migration, and differentiation, promoting tissue repair and regeneration, and at the same time, further driving the sustained effects of the antibacterial and antioxidant components contained in the hydrogel system. Specifically. In this technical solution, the acrylic acid (PAA) in the hydrogel system used contains rich carboxyl (–COOH) structures, which can release H+ in an aqueous environment to form an ionic polymer network. When the hydrogel is subjected to external mechanical stress (such as ultrasonic excitation), the local stress inside the network causes an uneven distribution of H+ concentration, forming an ion concentration gradient, which drives the directional diffusion of mobile ions; at the same time, the negatively charged PAA segments are restricted by the cross-linked network structure and cannot migrate, thereby generating a stable potential difference inside the material, reflecting a typical piezoelectric ion effect. This electrical response characteristic does not require the introduction of traditional inorganic piezoelectric fillers, but rather imparts piezoelectric functionality through the molecular structure of the material itself. It has good flexibility, biocompatibility and long-term stability, and is significantly superior to traditional piezoelectric hydrogel systems that rely on inorganic fillers.

[0012] Furthermore, the compound containing an amino group and a double bond is a combination of one or more of 2-(dimethylamino)ethyl methacrylate and N-isopropylacrylamide.

[0013] Furthermore, the halogenated hydrocarbon compound is a combination of one or more of 1-bromopropane, 1-bromobutane, and 1-chloroethane.

[0014] Furthermore, the quaternization reaction temperature is 20-100° C., and the reaction time is 6-24 hours.

[0015] Furthermore, the antioxidant component is a combination of one or more of tea polyphenols and tannic acid.

[0016] Furthermore, the crosslinking agent is a combination of one or more of N,N-methylenebisacrylamide and gelatin methacrylate; the photoinitiator is a combination of one or more of 2,4,6-trimethylbenzoyldiphenylphosphine oxide, α-ketoglutaric acid, and benzoyl peroxide.

[0017] Preferably, the crosslinking agent is N,N-methylenebisacrylamide; and the photoinitiator is 2,4,6-trimethylbenzoyldiphenylphosphine oxide.

[0018] Furthermore, each unit of the hydrogel precursor solution contains: 0 wt% to 30 wt% of acrylic acid, 0 wt% to 15 wt% of N-isopropylacrylamide, 0 wt% to 15 wt% of antioxidant, 0.5 wt‰ to 3 wt‰ of crosslinking agent, and 0.5 wt‰ to 1 wt‰ of photoinitiator.

[0019] Furthermore, in the step of ultrasonically inducing the piezoelectric effect, the ultrasonic power density used is 0 to 1 W / cm 2 , the pulse duty cycle is 0~100%.

[0020] Another object of the present invention is to provide an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel for use in wound or tissue repair. When used as a wound or tissue repair material, the hydrogel system provided by this technical solution can achieve active regulation of the wound microenvironment through the synergistic effects of the hydrogel system's endogenous antibacterial, antioxidant, and ultrasound-induced piezoelectric multiple functions, thereby achieving optimized effects on wound infection control, inflammation resolution, cell activation, and tissue remodeling. This provides a highly efficient, intelligent, and safe solution for complex wound or tissue repair.

[0021] Preferably, an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel is provided for use in the repair of diabetic infection wounds and articular cartilage defects; specifically, for chronic and difficult-to-heal wounds such as diabetic infection wounds, the hydrogel system provided by this technical solution can break through the healing stagnation period through the synergistic effect of antibacterial-antioxidant-ultrasound-induced piezoelectric multiple functions, thereby accelerating the repair of diabetic infection wounds; at the same time, the hydrogel system provided by this technical solution can promote osteogenic differentiation and promote tissue repair and regeneration through the generation of piezoelectric properties through ultrasound induction. At the same time, the endogenous antibacterial and antioxidant properties can also inhibit bacterial colonization at the implantation site, thereby improving the speed and effect of articular cartilage defect repair.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention synthesizes cationic quaternary ammonium salts as antibacterial ingredients through quaternization reaction, and combines it with a one-pot in-situ photocuring strategy to successfully prepare a multifunctional hydrogel with antibacterial, antioxidant and piezoelectric properties. This hydrogel has shown significant advantages in the fields of diabetic wound infection and articular cartilage repair: on the one hand, its efficient antibacterial properties can effectively prevent bacterial infection, while reducing oxidative stress and inflammatory response by scavenging reactive oxygen species (ROS), creating an optimal microenvironment for wound healing; on the other hand, the ultrasound-induced piezoelectric effect can directly regulate cell proliferation, migration and differentiation, and promote tissue repair and regeneration. Compared with the prior art, the present invention not only avoids the drug resistance problem of traditional antibiotics, but also significantly improves antioxidant properties and biocompatibility, and does not rely on external fillers that are easy to aggregate and have poor flexibility, and has excellent mechanical properties and long-term stability. In addition, the preparation process of the present invention is simple and efficient, the raw materials are easily available, and it is suitable for large-scale production, providing an innovative solution that is both efficient, safe and economical for diabetic wound infection and articular cartilage repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The hydrogel of Example 1-4 was subjected to a pulse duty cycle of 50% and an ultrasonic intensity of 0.5 W / cm 2 Output voltage curve below;

[0025] Figure 2 The hydrogel of Example 4 was fixed at an ultrasonic intensity of 0.5 W / cm 2 , output voltage curves when the pulse duty cycle is set to 10%, 20%, 50% and 100% respectively;

[0026] Figure 3 The hydrogel of Example 4 was fixed at a pulse duty cycle of 50% and an ultrasonic intensity of 0.1 W / cm 2 , 0.2W / cm 2 , 0.3W / cm 2 , 0.4W / cm 2 and 0.5W / cm 2 Output voltage curve;

[0027] Figure 4 These are digital photos of S. aureus and E. coli colonies surviving on agar plates of the hydrogels of the control group, Example 2, Example 3, and Example 4.

[0028] Figure 5 The antibacterial rates of the hydrogels of Examples 2, 3 and 4 against S. aureus and E. coli are shown.

[0029] Figure 6The ROS levels (detected by DCFH-DA probe) and O2 levels (detected by [Ru(dpp)3]Cl2 indicator) of L929 fibroblasts under different treatment conditions.

[0030] Figure 7 This is a photo of the wound healing process under the hydrogel treatment of Example 4.

[0031] Figure 8 This is a CT image of the hydrogel in Example 4 promoting cartilage regeneration. DETAILED DESCRIPTION

[0032] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present application belongs.

[0033] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.

[0034] The present invention will now be further described in conjunction with specific examples. The following examples are only intended to explain the present invention but do not limit the present invention. The test samples and test procedures used in the following examples include the following (if the specific experimental conditions are not specified in the examples, they are usually based on conventional conditions or the conditions recommended by the reagent company; the reagents, consumables, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources).

[0035] Example 1

[0036] This embodiment provides a method for preparing an ultrasound-induced piezoelectric hydrogel:

[0037] (1) Weighing 4.0 g of 10 wt% N-isopropylacrylamide, 0.01 g of 1 wt‰ N,N-methylenebisacrylamide, and 0.01 g of 1 wt‰ 2,4,6-trimethylbenzoyldiphenylphosphine oxide, dissolving them in deionized water and stirring them evenly to prepare a hydrogel precursor solution;

[0038] (2) Pour the hydrogel precursor solution prepared in step (1) into a polytetrafluoroethylene mold and cure it with a 365nm 10W ultraviolet curing light for 2 minutes to form a hydrogel.

[0039] Example 2

[0040] This embodiment provides a method for preparing an ultrasound-induced piezoelectric hydrogel:

[0041] (1) Weighing 2.86 mL of 30 wt% acrylic acid, 1.0 g of 10 wt% N-isopropylacrylamide, 0.01 g of 1 wt‰ N,N-methylenebisacrylamide, and 0.01 g of 1 wt‰ 2,4,6-trimethylbenzoyldiphenylphosphine oxide, dissolving them in deionized water and stirring them uniformly to prepare a hydrogel precursor solution;

[0042] (2) Pour the hydrogel precursor solution prepared in step (1) into a polytetrafluoroethylene mold and cure it with a 365nm 10W ultraviolet curing light for 2 minutes to form a hydrogel.

[0043] Example 3

[0044] This embodiment provides a method for preparing an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel:

[0045] (1) 15.72 g (0.10 mol) of 2-(dimethylamino)ethyl methacrylate, 13.52 g (0.11 mol) of 1-bromopropane, and 50 mL of ethyl acetate were added to a 250 mL round-bottom flask, stirred evenly, and reacted completely. The reaction mixture was then refluxed at 60° C. for 12 h. The refluxed reaction mixture was then filtered, and the collected precipitate was washed three times with anhydrous ether and dried under vacuum at room temperature to obtain a cationic quaternary ammonium salt.

[0046] (2) Weighing 0.1 g (1 wt%) of the cationic quaternary ammonium salt obtained in step (1), 2.86 mL (30 wt%) of acrylic acid, 1.0 g (10 wt%) of N-isopropylacrylamide, 0.01 g (1 wt‰) of N,N-methylenebisacrylamide, and 0.01 g (1 wt‰) of 2,4,6-trimethylbenzoyldiphenylphosphine oxide, dissolving them in deionized water and stirring evenly to prepare a hydrogel precursor solution;

[0047] (3) Pour the hydrogel precursor solution in step (3) into a polytetrafluoroethylene mold and cure it with a 365nm 10W ultraviolet curing light for 2 minutes to form a hydrogel.

[0048] Example 4

[0049] This embodiment is a preferred embodiment, which provides a method for preparing an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel:

[0050] (1) 15.72 g (0.10 mol) of 2-(dimethylamino)ethyl methacrylate, 13.52 g (0.11 mol) of 1-bromopropane, and 50 mL of ethyl acetate were added to a 250 mL round-bottom flask, stirred evenly, and reacted completely. The reaction mixture was then refluxed at 60° C. for 12 h. The refluxed reaction mixture was then filtered, and the collected precipitate was washed three times with anhydrous ether and dried under vacuum at room temperature to obtain a cationic quaternary ammonium salt.

[0051] (2) Weighing 0.1 g (1 wt%) of the cationic quaternary ammonium salt obtained in step (1), 2.86 mL (30 wt%) of acrylic acid, 1.0 g (10 wt%) of N-isopropylacrylamide, 1.0 g (10 wt%) of tannic acid, 0.01 g (1 wt‰) of N,N-methylenebisacrylamide, and 0.01 g (1 wt‰) of 2,4,6-trimethylbenzoyldiphenylphosphine oxide, dissolving them in deionized water and stirring evenly to prepare a hydrogel precursor solution;

[0052] (3) Pour the hydrogel precursor solution in step (3) into a polytetrafluoroethylene mold and cure it with a 365nm 10W ultraviolet curing light for 2 minutes to form a hydrogel.

[0053] Effect Example 1

[0054] In this example, a Rigol DS1102E oscilloscope was used to test the output voltage of the hydrogels prepared in Examples 1-4 under ultrasonic stimulation to characterize their electrical output performance. The specific testing method is as follows: The hydrogel sample was cut into a circular shape with a diameter of 10 mm, clamped between a pair of copper electrodes, and sealed with Ecoflex to form a test device. The assembled hydrogel device was placed under the ultrasonic transducer and a Mettler was used. The 740 digital therapeutic ultrasound system generates ultrasonic stimulation with a probe area of 5cm 2 , the frequency was 1 MHz, the pulse duty cycle was set to 50%, and the ultrasonic intensity was 0.5 W / cm 2 The output voltage is measured in real time by a Rigol DS1102E oscilloscope. The test results are as follows: Figure 1As shown, the hydrogels prepared in Examples 1-4 all exhibited a certain piezoelectric effect under ultrasonic induction, indicating that the hydrogels prepared by this technical solution can efficiently convert the mechanical energy generated by ultrasound into electrical signals, proving its energy conversion ability under ultrasonic induction. Furthermore, Example 1 only contains N-isopropylacrylamide, a crosslinker, and a photoinitiator; Example 2 adds acrylic acid compared to Example 1, Example 3 introduces a cationic quaternary ammonium salt after quaternization reaction on the basis of Example 2, and Example 4 further adds tannic acid as an antioxidant on the basis of Example 3. The piezoelectric properties of the hydrogels formed in Examples 1-4 gradually increase, indicating that there is a synergistic effect between the acrylic acid monomer, cationic quaternary ammonium salt, and antioxidant added to the material system provided by this technical solution for forming antibacterial and antioxidant ultrasonically induced piezoelectric hydrogels, thereby enhancing the piezoelectric properties of the formed hydrogels.

[0055] Effect Example 2

[0056] This example tests the electrical output performance of the hydrogel prepared in Example 4 under different pulse duty cycle conditions. The test method is as follows: The hydrogel sample is cut into a circular shape with a diameter of 10 mm, clamped between a pair of copper electrodes, and sealed with Ecoflex to assemble a test device. The assembled hydrogel device is placed under the ultrasonic transducer and the device is tested using a Mettler The 740 digital therapeutic ultrasound system generates ultrasonic stimulation with a probe area of 5cm 2 , the frequency is 1 MHz, and the ultrasonic intensity is fixed at 0.5 W / cm 2 The pulse duty cycle was set to 10%, 20%, 50%, and 100%, respectively. The output voltage was measured in real time using a Rigol DS1102E oscilloscope. The test results showed that the duration of the voltage signal in the output signal increased significantly with increasing pulse duty cycle, fully demonstrating the hydrogel's stable piezoelectric response under different pulse duty cycle conditions.

[0057] Effect Example 3

[0058] This example tests the electrical output performance of the hydrogel prepared in Example 4 under different ultrasound intensities. The test method is as follows: The hydrogel sample is cut into a circular shape with a diameter of 10 mm, clamped between a pair of copper electrodes, and sealed with Ecoflex to assemble a test device. The assembled hydrogel device is placed under the ultrasonic transducer and the ultrasonic wave is measured using a Mettler microscope. Ultrasonic stimulation was generated using a 740 digital therapeutic ultrasound system with a probe area of 5 cm2, a frequency of 1 MHz, a pulse duty cycle fixed at 50%, and ultrasound intensities set to 0.1 W / cm2, 0.2 W / cm2, 0.3 W / cm2, 0.4 W / cm2, and 0.5 W / cm2. The output voltage was measured in real time using a Rigol DS1102E oscilloscope. The test results showed that the electrical output performance of the hydrogel increased linearly with increasing ultrasound intensity, reaching a peak at 0.5 W / cm2. 2 The maximum value was reached at different intensities, proving that the hydrogel has efficient energy conversion capability under different ultrasound intensities.

[0059] Effect Example 4

[0060] This effect example tests the antibacterial properties of the hydrogels prepared in Examples 2-4 against Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli). The test method is as follows: the antibacterial properties of the hydrogels were evaluated by the plate count method to determine the number of colony forming units (CFU) on the agar plate. During the experiment, the sterilized hydrogels (diameter: 10 mm) were co-cultured with 300 μL of S.aureus or E.coli suspension (bacterial liquid concentration: 107 CFU·mL-1) in a 48-well culture plate for 12 hours. Among them, the untreated bacterial liquid served as the control group. After the culture was completed, the supernatant of each sample was taken and diluted 106 times with sterile phosphate buffer solution, and 20 μL of the diluted bacterial suspension was evenly spread on the agar plate, and the culture was continued for 12 hours, and the antibacterial rate was calculated by colony counting. The results showed that compared with the control group and Example 2, Examples 3 and 4 exhibited significant antibacterial effects on S.aureus and E.coli, such as Figure 4 As shown in the figure, only a very small number of colonies survive. Figure 5 As shown, statistical analysis shows that the antibacterial rates of Example 3 and Example 4 are both close to 100%, proving that the hydrogels prepared in Examples 3-4 have good active antibacterial effects.

[0061] Effect Example 5

[0062] This example tests the antioxidant properties of the hydrogels prepared in Examples 2-4. The test method is as follows: L929 fibroblasts (density: 5×104 cells·mL -1) were seeded in a 24-well culture plate and cultured for 24 hours. After culturing, they were co-cultured with 20 mg of hydrogel for 24 hours under an oxidative stress environment (100 μM hydrogen peroxide). In order to detect the level of intracellular reactive oxygen species (ROS), after the end of culture, the cells were incubated with dichlorofluorescein diacetate (DCFH-DA, 10 μM) for 20 minutes and washed 3 times with PBS. The DCFH-DA fluorescence signal was detected by fluorescence microscopy and microplate reader. In addition, to evaluate the intracellular oxygen content, 100 μL of 10 μg mL-1 was added to each well after co-culture with the hydrogel. -1 The oxygen quenching fluorescent probe [Ru(dpp)3]Cl2 solution was incubated for 12 hours. After all samples were washed with PBS, the fluorescence signal of [Ru(dpp)3]Cl2 was measured by fluorescence microscopy. Compared with the control group and Examples 2 and 3, only a weak fluorescence signal was detected in the cells treated with Example 4, while Figure 6 As shown, the control group, Example 2 and Example 3 all showed strong fluorescence, that is, the results showed that the hydrogel prepared in Example 4 had a more efficient ability to scavenge intracellular reactive oxygen species.

[0063] Effect Example 6

[0064] This effect example tests the effect of the hydrogel prepared in Example 4 on promoting wound healing in vivo.

[0065] To evaluate the in vivo effect of the hydrogel in Example 4 on wound healing, a diabetic rat wound model infected with Staphylococcus aureus (S. aureus) was constructed. The specific method was as follows: a circular full-thickness skin defect with a diameter of 10 mm was prepared on the back of the diabetic rat, and then 100 μL of S. aureus suspension (bacterial concentration: 108 CFU·mL) was inoculated into the wound. -1 ) and continued to culture for 1 day. The experimental rats were randomly divided into 4 groups (n=3) and received different treatments: control group: the wound was covered with ordinary gauze, without other treatment; ultrasound group: ultrasound treatment for 3 minutes every day; hydrogel group: the wound was covered with hydrogel, without other treatment; ultrasound + hydrogel group: the wound was covered with hydrogel and ultrasound was performed for 3 minutes every day. The wound healing status was recorded using a digital camera. Figure 7 As shown, it shows that the hydrogel combined with ultrasound treatment group has an excellent healing effect.

[0066] Effect Example 7

[0067] This effect example tests the effect of the hydrogel prepared in Example 4 on promoting cartilage regeneration in vivo.

[0068] In order to evaluate the in vivo effect of the hydrogel in Example 4 on cartilage regeneration, a rabbit knee cartilage defect model was established. During the experiment, the experimental rabbits were placed in a supine position, the knee joint area was shaved and disinfected, and then a medial parapatellar arthrotomy was performed to expose the knee joint. A standardized defect with a diameter of approximately 4 mm and a depth of approximately 2 mm was prepared on the surface of the femoral condyle articular cartilage. Subsequently, the hydrogel was directly filled and attached to the cartilage defect, or the defect was kept vacant in the control group. After the operation was completed, the muscles and skin were sutured layer by layer, and the surgical area was sterilized to prevent infection. The results are shown in Figure 2. Figure 8 As shown, the hydrogel group had an excellent effect in promoting cartilage regeneration.

[0069] Obviously, the above embodiments of the present invention are merely examples for the purpose of clearly illustrating the technical solutions of the present invention, and are not intended to limit the specific implementation methods of the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the claims of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing an antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel, characterized in that: Including steps: (1) through a quaternization reaction, a compound containing an amine group and a double bond is reacted with a halogenated hydrocarbon compound to synthesize a cationic quaternary ammonium salt; (2) uniformly mixing the cationic quaternary ammonium salt, antioxidant component, acrylic acid, N-isopropylacrylamide, crosslinking agent and photoinitiator obtained in step (1) to obtain a hydrogel precursor solution; (3) The hydrogel precursor solution in step (2) is solidified by a photocuring process to obtain an ionic hydrogel with antibacterial and antioxidant properties, wherein the hydrogel can generate a piezoelectric effect under ultrasound induction.

2. The preparation method according to claim 1, characterized in that In step (1), the compound containing an amino group and a double bond is a combination of one or more of 2-(dimethylamino)ethyl methacrylate and N-isopropylacrylamide.

3. The preparation method according to claim 1, characterized in that In step (1), the halogenated hydrocarbon compound is a combination of one or more of 1-bromopropane, 1-bromobutane, and 1-chloroethane.

4. The preparation method according to claim 1, characterized in that In step (2), the cross-linking agent is a combination of one or more of N,N-methylenebisacrylamide and gelatin methacrylate; The photoinitiator is a combination of one or more of 2,4,6-trimethylbenzoyldiphenylphosphine oxide, α-ketoglutaric acid, and benzoyl peroxide.

5. The preparation method according to claim 1, characterized in that In step (2), each unit of hydrogel precursor solution contains: 0wt% to 30wt% of acrylic acid, 0wt% to 15wt% of N-isopropylacrylamide, 0wt% to 15wt% of antioxidant, 0.5wt‰ to 3wt‰ of crosslinking agent, and 0.5wt‰ to 1wt‰ of photoinitiator.

6. The preparation method according to claim 1, characterized in that In step (3), in the step of ultrasonically inducing the piezoelectric effect, the ultrasonic power density used is 0 to 1 W / cm 2 , the pulse duty cycle is 0~100%.

7. The antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel obtained by the preparation method according to any one of claims 1 to 6.

8. Use of the antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel according to claim 7 in wound repair or tissue repair.

9. Use of the antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel according to claim 8 in repairing diabetic infected wounds.

10. Use of the antibacterial and antioxidant ultrasound-induced piezoelectric hydrogel according to claim 9 in repairing articular cartilage defects.

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