Ultrasonic response piezoelectric hydrogel and its preparation method and application

Abstract

The present invention discloses an ultrasonically responsive piezoelectric hydrogel, a preparation method thereof, and applications thereof. The hydrogel comprises sodium potassium niobate nanowires whose surfaces are modified with dopamine and hyaluronic acid grafted with dopamine. The hydrogel has excellent piezoelectric properties and is injectable, degradable, and biocompatible. It has potential application prospects in the biomedical field and clinical practice.

Description

Technical Field

[0001] The present invention belongs to the technical field of bioelectronic medical equipment, and in particular relates to an ultrasonically responsive piezoelectric hydrogel and a preparation method and application thereof. Background Art

[0002] With improvements in living standards and medical technology, my country is rapidly entering an aging society. As the physiological functions and reflexes of the elderly decline, the demand for transplants following various tissue injuries is increasing. Tissue engineering and regenerative medicine are gradually becoming important developments in clinical medicine, and research on related products and technologies will become a hot topic in future medical alternatives. Tissue engineering is a scientific discipline that uses specific bioactive cells, tissues, or scaffold materials to construct tissues and organs in vitro or in vivo to maintain, repair, or induce tissue regeneration and improve specific tissue function. Vigorously developing basic research in tissue engineering and continuously innovating tissue engineering technologies will significantly enhance China's international status and market competitiveness in this field, providing new impetus for the arrival of an aging society in China. Regenerative and tissue engineering strategies that combine growth factors / small molecule therapies, biomaterial scaffolds, and stem cells / osteoblasts have become a key research area.

[0003] Currently, common treatments include cell transplantation, tissue engineering scaffolds, and electrical stimulation rehabilitation. Neurological diseases are primarily caused by the death or loss of function of nerve cells. In the adult mammalian nervous system, spontaneous replacement of endogenous neurons and reorganization of the neural network rarely occur. Common neural stem cells include induced pluripotent stem cells, mesenchymal stem cells, and Schwann cells. Their multipotent differentiation capacity and secretion of various cytokines and growth factors promote axon regeneration and restore interneuronal communication. However, limited sources of transplantable cells, high costs, and low cell viability after transplantation severely limit the clinical application of this technology. For example, after spinal cord injury, its integrity is destroyed, making it difficult for spinal cord nerve tissue to regenerate, resulting in the formation of cysts and loss of support for the uninjured portion of the spinal cord. Studies have shown that without any treatment, the diameter of the spinal cord at the injured site is significantly smaller than that of the normal site. Implanted tissue engineering scaffolds can bridge the injury defect, prevent glial scar formation, and provide contact guidance for axonal regeneration from the injury site to distal sites. Furthermore, an ideal scaffold can minimize local inflammatory responses and inhibit cell apoptosis or necrosis. Tissue engineering scaffolds not only provide ample space for nervous system cell survival and material exchange but also, to a certain extent, provide physical guidance for axonal growth. The mechanical properties of the scaffold can compensate for the lack of mechanical support caused by nerve injury, providing contact guidance for directional axonal growth, thereby improving the accuracy of nerve apposition. They also provide sufficient mechanical support for regenerating nerve fibers, reduce tension on surgical sutures, and prevent the ingress of scar tissue. Furthermore, the difficulty in treating tissue injuries is largely attributed to the central nervous system's inhibitory environment for axonal growth and poor neuronal regeneration capacity. Spontaneous axonal regeneration at the site of injury is limited, necessitating the development of methods to promote nerve regeneration. Neuroelectric stimulation is considered a promising approach. Research has shown that restoring bioelectrical signal transmission at the injury site can guide axons in the correct direction, establishing the structural connections and information pathways necessary for functional connectivity. Currently, electrical stimulation has been demonstrated to promote the healing of damaged neural tissue both in vitro and in vivo, with experimental results demonstrating that electrical stimulation can enhance the differentiation of neural stem cells. Several research teams have developed a technique to connect healthy nerves in the brain and spinal cord. Using spinal cord electrical stimulation, they successfully restored movement in the partially paralyzed arms of three monkeys. Electrical stimulation plays a key role in regulating cell behavior and tissue development, physiology, and pathophysiology. Furthermore, electrical stimulation can accelerate tissue formation by improving local blood supply and increasing the delivery of nutrients and metabolites to local tissues. Therefore, tissue engineering scaffolds with electrical stimulation capabilities are of great significance for tissue engineering repair therapies.

[0004] Piezoelectric materials are intelligent materials that generate electrical energy in response to external forces. They can serve as self-powered neural tissue engineering scaffolds, leveraging in situ stimulation via body movement or external mechanical vibration to promote neural growth, proliferation, and differentiation. Therefore, the development of biodegradable piezoelectric materials is crucial. They can generate electrical charge to promote bone regeneration and safely degrade to promote cell infiltration and tissue growth. Currently, the electrical signals generated by biodegradable piezoelectric scaffolds, which rely on the mechanical forces of cells and the animal body, are relatively weak and poorly controllable. Ultrasound, a high-frequency mechanical wave, transmits energy with minimal attenuation to subcutaneous tissue and penetrates deep, enabling direct effects on subcutaneous tissue, nerves, and internal organs. Therefore, combining biodegradable piezoelectric tissue engineering materials with programmable ultrasound technology can effectively control the timing and intensity of in vivo electrical stimulation, holding great potential for neural tissue engineering. Therefore, the exploration of biodegradable piezoelectric materials with excellent piezoelectric properties is of great significance for tissue engineering. Summary of the Invention

[0005] The present invention aims to address, at least to some extent, one of the technical problems in the related art. To this end, the present invention provides an ultrasonically responsive piezoelectric hydrogel, its preparation method, and its application. This hydrogel exhibits excellent piezoelectric properties and is injectable, biodegradable, and biocompatible, offering potential applications in biomedicine and clinical settings.

[0006] In one aspect, the present invention provides an ultrasonically responsive piezoelectric hydrogel. According to an embodiment of the present invention, the ultrasonically responsive piezoelectric hydrogel comprises dopamine-modified potassium sodium niobate nanowires (KNN@PDA) and dopamine-grafted hyaluronic acid (HA-DA).

[0007] Hyaluronic acid and potassium sodium niobate nanowires are abundant in source, low in price and have good biocompatibility. The hydrogel prepared with hyaluronic acid and potassium sodium niobate nanowires has excellent biocompatibility. Secondly, potassium sodium niobate nanowires have good piezoelectric properties. The inventors found that if bulk piezoelectric materials are used, their hardness is too high to be suitable for implantation. Potassium sodium niobate nanowires are small in size and can effectively avoid surgical trauma. However, piezoelectric materials flow randomly with body fluids in tissues and are not concentrated enough, so the stimulation effect is not obvious enough. Hyaluronic acid has good fluidity and can be squeezed and injected for implantation. It is easy to operate, easy to shape, has a low risk of infection, and reduces pain for patients. At the same time, hyaluronic acid is the main component of the extracellular matrix of the brain and spinal cord. It can be used as a scaffold material for treating central nervous system injuries. Therefore, A hydrogel is prepared using potassium sodium niobate nanowires and hyaluronic acid, which have good piezoelectric properties. The hydrogel not only has excellent piezoelectric properties and good biocompatibility, but is also injectable and degradable. On the other hand, the inventors found that by grafting dopamine (DA) molecules onto hyaluronic acid (HA) molecules, the hyaluronic acid-dopamine hydrogel has good cell adhesion properties. The surface of the potassium sodium niobate nanowires is modified with dopamine, which can improve the dispersibility and biocompatibility of the potassium sodium niobate nanowires (KNN). As a result, the uniformly dispersed KNN@PDA nanowires are interwoven and distributed in the HA-DA hydrogel matrix, improving the piezoelectricity of the hydrogel. When the hydrogel is injected into the body, it can respond to in vitro ultrasound in real time to generate alternating current pulses, thereby directly stimulating nerve tissue and promoting nerve growth, proliferation, differentiation, etc. As a result, the hydrogel has excellent piezoelectric properties, is injectable, degradable, and has good biocompatibility. It has potential application prospects in the biomedical field and clinically.

[0008] In addition, the ultrasonically responsive piezoelectric hydrogel according to the above embodiment of the present invention may also have the following technical solutions:

[0009] In some embodiments of the present invention, the mass ratio of the sodium potassium niobate nanowires with dopamine-modified surfaces to the dopamine-grafted hyaluronic acid is (2-10):(20-35). Thus, the hydrogel has excellent piezoelectric properties.

[0010] In some embodiments of the present invention, the method for preparing the potassium sodium niobate nanowires whose surface is modified with dopamine comprises:

[0011] (1) Niobium pentoxide, potassium chloride, and potassium carbonate are mixed and ball-milled, followed by a first calcination to obtain potassium sodium niobate precursor nanowires, and then a nitric acid solution is added, stirred, washed with ultrapure water several times, and dried, followed by a second calcination. The product after the second calcination is ground and mixed with sodium chloride, sodium carbonate, potassium chloride, and potassium carbonate, and then calcined for a third time to obtain potassium sodium niobate nanomaterials; (2) The potassium sodium niobate nanomaterials are added to a buffer solution and stirred, and then dopamine hydrochloride is added and stirred, washed with water, centrifuged, and dried to obtain potassium sodium niobate nanowires with dopamine modified surfaces. In this way, potassium sodium niobate nanowires with good piezoelectric properties and dopamine modified surfaces can be prepared.

[0012] In some embodiments of the present invention, in step (1), the molar ratio of niobium pentoxide, potassium chloride, and potassium carbonate is (1-1.5): (10-15): (0.3-1).

[0013] In some embodiments of the present invention, in step (1), the temperature of the first calcination is 800-1000° C., and the time is 2-4 hours.

[0014] In some embodiments of the present invention, in step (1), the temperature of the second calcination is 500-600° C., and the time is 1-1.5 h.

[0015] In some embodiments of the present invention, in step (1), the mass ratio of the product after the second calcination, sodium chloride, sodium carbonate, potassium chloride and potassium carbonate is (1-2): (3-4): (0.2-0.5): (3-4): (0.2-0.5).

[0016] In some embodiments of the present invention, in step (1), the temperature of the third calcination is 800-1000° C., and the time is 5-10 minutes.

[0017] In some embodiments of the present invention, the method for preparing the dopamine-grafted hyaluronic acid comprises:

[0018] After dissolving 0.8g to 1.2g of hyaluronic acid in 125mL of water, a base is added to adjust the pH of the hyaluronic acid solution to 5.0 to 6.0, then 7mol to 8mol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 7mol to 8mol of N-hydroxysuccinimide are added with stirring, and finally dopamine is added and stirred at room temperature for 10h to 18h, followed by dialysis to obtain dopamine-grafted hyaluronic acid. Dopamine-grafted hyaluronic acid can be prepared in this manner.

[0019] In a second aspect of the present invention, a method for preparing the ultrasonically responsive piezoelectric hydrogel is provided. According to an embodiment of the present invention, the method comprises:

[0020] The sodium potassium niobate nanowires whose surfaces are modified with dopamine, dopamine-grafted hyaluronic acid, horseradish peroxidase and a hydrogen peroxide solution are mixed, stirred and allowed to stand to obtain an ultrasonically responsive piezoelectric hydrogel.

[0021] The inventors discovered that using horseradish peroxidase (HRP) and hydrogen peroxide as enzymatic crosslinking reagents can oxidatively couple and crosslink dopamine-modified potassium sodium niobate nanowires with catechol groups on the surface of dopamine-grafted hyaluronic acid, thereby preparing an injectable composite hydrogel. This method can be used to prepare an ultrasonically responsive piezoelectric hydrogel that exhibits excellent piezoelectric properties, is injectable, biodegradable, and has good biocompatibility.

[0022] In addition, the method for preparing ultrasonically responsive piezoelectric hydrogel according to the above embodiment of the present invention may also have the following technical features:

[0023] In some embodiments of the present invention, the mass ratio of the dopamine-modified potassium sodium niobate nanowires, the dopamine-grafted hyaluronic acid, the horseradish peroxidase, and the hydrogen peroxide solution is (2-10):(20-35):(0.1-0.3):(5-8). Thus, an ultrasonically responsive piezoelectric hydrogel with excellent piezoelectric properties, injectability, biodegradability, and good biocompatibility can be prepared.

[0024] In some embodiments of the present invention, the concentration of the hydrogen peroxide solution is 20-30%.

[0025] In some embodiments of the present invention, the temperature of the standing still is 30-40° C., and the standing still time is 3-10 minutes. Thus, an ultrasonically responsive piezoelectric hydrogel having excellent piezoelectric properties, injectability, degradability, and good biocompatibility can be prepared.

[0026] In its third aspect, the present invention provides a power generation device. According to an embodiment of the present invention, the power generation device includes a positive electrode, a negative electrode, and a piezoelectric composite film. The positive electrode and the negative electrode are located on either side of the piezoelectric composite film, respectively. The piezoelectric composite film is prepared using the ultrasonically responsive piezoelectric hydrogel described above or the ultrasonically responsive piezoelectric hydrogel obtained by the above method. As a result, the power generation device exhibits excellent power generation performance.

[0027] In a fourth aspect of the present invention, the present invention proposes the use of the above-mentioned ultrasonically responsive piezoelectric hydrogel or the ultrasonically responsive piezoelectric hydrogel prepared by the above-mentioned method in neural tissue engineering, biomedicine or clinical treatment.

[0028] In a fifth aspect of the present invention, the present invention proposes the use of the above-mentioned power generation device in nerve stimulation, nerve tissue repair or wireless implantation.

[0029] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments with reference to the accompanying drawings, in which:

[0031] Figure 1 This is a schematic diagram of an animal experiment of hydrogel injection according to an embodiment of the present invention;

[0032] Figure 2 is a SEM electron microscope image of potassium sodium niobate nanowires (KNN) according to Example 1 of the present invention;

[0033] Figure 3 is a SEM electron microscope image of the piezoelectric hydrogel of Example 1 of the present invention;

[0034] Figure 4 1 is a graph showing the in vitro degradation results of the piezoelectric hydrogel of Example 1 of the present invention;

[0035] Figure 5 This is a physical picture of the power generation device prepared in Example 2 of the present invention;

[0036] Figure 6 This is a graph of the output voltage of the piezoelectric composite film prepared in Example 2 of the present invention. DETAILED DESCRIPTION

[0037] The embodiments of the present invention are described in detail below, which are intended to explain the present invention but are not to be construed as limiting the present invention.

[0038] In one aspect, the present invention provides an ultrasonically responsive piezoelectric hydrogel. According to an embodiment of the present invention, the ultrasonically responsive piezoelectric hydrogel comprises dopamine-modified potassium sodium niobate nanowires (KNN@PDA) and dopamine-grafted hyaluronic acid (HA-DA).

[0039] Hyaluronic acid and potassium sodium niobate nanowires are abundant in source, low in price and have good biocompatibility. The hydrogel prepared with hyaluronic acid and potassium sodium niobate nanowires has excellent biocompatibility. Secondly, potassium sodium niobate nanowires have good piezoelectric properties. The inventors found that if bulk piezoelectric materials are used, their hardness is too high to be suitable for implantation. Potassium sodium niobate nanowires are small in size and can effectively avoid surgical trauma. However, piezoelectric materials flow randomly with body fluids in tissues and are not concentrated enough, so the stimulation effect is not obvious enough. Hyaluronic acid has good fluidity and can be squeezed and injected for implantation. It is easy to operate, easy to shape, has a low risk of infection, and reduces pain for patients. At the same time, hyaluronic acid is the main component of the extracellular matrix of the brain and spinal cord. It can be used as a scaffold material for treating central nervous system injuries. Therefore, A hydrogel is prepared using potassium sodium niobate nanowires and hyaluronic acid, which have good piezoelectric properties. The hydrogel not only has excellent piezoelectric properties and good biocompatibility, but is also injectable and degradable. On the other hand, the inventors found that by grafting dopamine (DA) molecules onto hyaluronic acid (HA) molecules, the hyaluronic acid-dopamine hydrogel has good cell adhesion properties. The surface of the potassium sodium niobate nanowires is modified with dopamine, which can improve the dispersibility and biocompatibility of the potassium sodium niobate nanowires (KNN). As a result, the uniformly dispersed KNN@PDA nanowires are interwoven and distributed in the HA-DA hydrogel matrix, improving the piezoelectricity of the hydrogel. When the hydrogel is injected into the body, it can respond to in vitro ultrasound in real time to generate alternating current pulses, thereby directly stimulating nerve tissue and promoting nerve growth, proliferation, differentiation, etc. As a result, the hydrogel has excellent piezoelectric properties, is injectable, degradable, and has good biocompatibility. It has potential application prospects in the biomedical field and clinically.

[0040] It should be noted that the ultrasonic response processing method is a conventional method in this field. Those skilled in the art can select specific ultrasonic conditions or equipment according to actual conditions. Ultrasonic waves are high-frequency mechanical waves. The stronger the ultrasonic power, the higher the hydrogel output. For example, this application uses external programmable wireless ultrasonic equipment for stimulation to generate electrical signals of specific waveforms. By controlling the power density, pulse width, and stimulation frequency of the ultrasonic waves, a pulse voltage and current with a specific pulse width and stimulation frequency is output. Compared with the electrical stimulation direction of the traditional inserted electrode, it has significant advantages such as non-destructive, reduced infection, and greater safety, and has potential uses in the field of cell scaffolds and tissue engineering scaffold materials.

[0041] According to an embodiment of the present invention, the mass ratio of the surface-modified potassium sodium niobate nanowires with dopamine to the dopamine-grafted hyaluronic acid is (2-10): (20-35). The inventors found that if the mass proportion of the surface-modified potassium sodium niobate nanowires with dopamine in the hydrogel is too large, the hydrogel will not easily form a gel; if the mass proportion of the surface-modified potassium sodium niobate nanowires with dopamine in the hydrogel is too small, the piezoelectric performance will be greatly weakened. Therefore, the present application adopts a mass ratio of the surface-modified potassium sodium niobate nanowires with dopamine to the dopamine-grafted hyaluronic acid of (2-10): (20-35), and the resulting hydrogel has excellent piezoelectric properties.

[0042] According to an embodiment of the present invention, a method for preparing potassium sodium niobate nanowires with dopamine modified surfaces includes: (1) mixing niobium pentoxide, potassium chloride, and potassium carbonate, ball milling, and then calcining for the first time to obtain potassium sodium niobate precursor nanowires, then adding niobium pentoxide, stirring, washing with ultrapure water for multiple times, and drying, followed by calcining for the second time, mixing the product after the second calcination with sodium chloride, sodium carbonate, potassium chloride, potassium carbonate, and grinding, and then calcining for the third time to obtain potassium sodium niobate nanomaterials; (2) adding the potassium sodium niobate nanomaterials to a buffer solution and stirring, then adding dopamine hydrochloride and stirring, washing with water, centrifuging, and drying to obtain potassium sodium niobate nanowires with dopamine modified surfaces. In this way, potassium sodium niobate nanowires with good piezoelectric properties and dopamine modified surfaces can be prepared. Some specific process conditions in the preparation process are as follows:

[0043] The molar ratio of niobium pentoxide, potassium chloride and potassium carbonate is (1-1.5):(10-15):(0.3-1); the temperature of the first calcination is 800-1000°C and the time is 2-4 hours; the temperature of the second calcination is 500-600°C and the time is 1-1.5 hours; the mass ratio of the product after the second calcination, sodium chloride, sodium carbonate, potassium chloride and potassium carbonate is (1-2):(3-4):(0.2-0.5):(3-4):(0.2-0.5); the temperature of the third calcination is 800-1000°C and the time is 5-10 minutes.

[0044] According to an embodiment of the present invention, a method for preparing dopamine-grafted hyaluronic acid includes: dissolving 0.8 g to 1.2 g of hyaluronic acid in 125 mL of water, adding alkali to adjust the pH of the hyaluronic acid solution to 5.0 to 6.0, then adding 7 mol to 8 mol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 7 mol to 8 mol of N-hydroxysuccinimide and stirring, and finally adding dopamine and stirring at room temperature for 10 h to 18 h and then dialyzing to obtain dopamine-grafted hyaluronic acid.

[0045] In a second aspect of the present invention, a method for preparing the ultrasonically responsive piezoelectric hydrogel is provided. According to an embodiment of the present invention, the method comprises:

[0046] The sodium potassium niobate nanowires whose surfaces are modified with dopamine, dopamine-grafted hyaluronic acid, horseradish peroxidase and a hydrogen peroxide solution are mixed, stirred and allowed to stand to obtain an ultrasonically responsive piezoelectric hydrogel.

[0047] The inventors discovered that using horseradish peroxidase (HRP) and hydrogen peroxide as enzymatic crosslinking reagents, they could oxidatively couple and crosslink dopamine-modified potassium sodium niobate nanowires with catechol groups on the surface of dopamine-grafted hyaluronic acid, creating an injectable composite hydrogel. This method can be used to produce an ultrasonically responsive piezoelectric hydrogel with excellent piezoelectric properties, injectability, biodegradability, and good biocompatibility.

[0048] It should be noted that the hydrogel prepared above is added to a syringe and injected into the injured spinal cord. After applying an ultrasonic coupling agent to the body's epidermis, ultrasonic stimulation is given. Specifically, Figure 1 As shown, first, the T8-T10 segments of the rat spinal nerves need to be exposed, and then the T9 segment is completely cut off by 2 mm and filled with the hydrogel of the present application. After suturing, it is restored for one week. After applying ultrasonic coupling glue at the implantation site, under external ultrasonic stimulation, the alternating current generated by the piezoelectric hydrogel can promote the repair of nerve tissue damage.

[0049] According to an embodiment of the present invention, the added mass ratio of potassium sodium niobate nanowires with dopamine modified surfaces, dopamine grafted hyaluronic acid, horseradish peroxidase and hydrogen peroxide solution is (2-10): (20-35): (0.1-0.3): (5-8). The inventors found that if the added mass of horseradish peroxidase and hydrogen peroxide solution is too small, it is not easy to form a gel; if the added mass of horseradish peroxidase and hydrogen peroxide solution is too large, the gelation time will be accelerated, which is not conducive to later injectable implantation. Therefore, the present application adopts potassium sodium niobate nanowires with dopamine modified surfaces, dopamine grafted hyaluronic acid, horseradish peroxidase and hydrogen peroxide solution in the above-mentioned addition ratio range to prepare an ultrasonically responsive piezoelectric hydrogel with excellent piezoelectric properties, which is injectable, degradable and has good biocompatibility. Specifically, the concentration of hydrogen peroxide is 20-30%.

[0050] According to an embodiment of the present invention, the standing temperature is 30-40°C, and the standing time is 3-10 minutes. The inventors found that if the standing temperature is too low, it is difficult to form a gel; if the standing temperature is too high, the gelation time is too fast, which is not conducive to the injection of the hydrogel; if the standing time is too short, no gel is formed; if the standing time is too long, the gel polymerization is not conducive to the injection of the hydrogel. Therefore, the standing temperature used in this application is 30-40°C and the standing time is 3-10 minutes, which can prepare an ultrasonically responsive piezoelectric hydrogel with excellent piezoelectric properties, which is injectable, degradable, and has good biocompatibility.

[0051] The third aspect of the present invention provides a power generation device. According to an embodiment of the present invention, the power generation device includes a positive electrode, a negative electrode and a piezoelectric composite film, wherein the positive electrode and the negative electrode are respectively located on both sides of the piezoelectric composite film, and the piezoelectric composite film is prepared using the above-mentioned ultrasonic responsive piezoelectric hydrogel or the ultrasonic responsive piezoelectric hydrogel obtained by the above-mentioned method. As a result, the power generation device has excellent power generation performance. It should be noted that the preparation method of the power generation device is a conventional method in the field, and those skilled in the art can make a selection based on the specific piezoelectric composite film material, such as electrospinning or 3D printing.

[0052] In a fourth aspect of the present invention, the present invention proposes the use of the above-mentioned ultrasonically responsive piezoelectric hydrogel or the ultrasonically responsive piezoelectric hydrogel prepared by the above-mentioned method in neural tissue engineering, biomedicine or clinical treatment.

[0053] In a fifth aspect of the present invention, the present invention proposes the use of the above-mentioned power generation device in nerve stimulation, nerve tissue repair or wireless implantation.

[0054] The present invention is described below with reference to specific examples. It should be noted that these examples are merely illustrative and do not limit the present invention in any way.

[0055] Example 1

[0056] (1) Preparation of dopamine-modified potassium sodium niobate nanowires

[0057] The raw materials, niobium pentoxide, potassium chloride, and potassium carbonate, were weighed in a molar ratio of 1 / 15 / 1, wet-ball milled for 1 hour, dried, and calcined at 1000°C for 3 hours. The product was washed multiple times with deionized water and dried to produce a potassium sodium niobate (KNN) precursor. The potassium sodium niobate precursor was added to a nitric acid solution and stirred at room temperature or under heating for 48 hours. The solution was then washed with hot deionized water until neutral, dried, and calcined at 550°C for 1 hour. The calcined product was then mixed with sodium carbonate, potassium carbonate, potassium chloride, and sodium chloride in a mass ratio of 1 / 3.5 / 3.5 / 0.34 / 0.3. The mixture was then calcined at 850°C for 10 minutes. The calcined product was then washed with hot deionized water and dried to produce potassium sodium niobate nanowires (KNN).

[0058] The above-mentioned potassium sodium niobate nanowires (KNN) were added to a Tris-HCl buffer solution with a pH of 8.5 and stirred for 1 hour, and then dopamine hydrochloride was added and stirred for 6 hours. Finally, the solution was washed with water, centrifuged, and dried to obtain potassium sodium niobate nanowires with dopamine modified surfaces (KNN@PDA).

[0059] (2) Preparation of dopamine-grafted hyaluronic acid

[0060] Dissolve 1g of hyaluronic acid in 125mL of deionized water, add sodium hydroxide (0.1M) to adjust the pH of the hyaluronic acid solution to 5.0-6.0, then slowly add 7mol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 7mol of N-hydroxysuccinimide, stirring to ensure that the carboxyl groups are fully activated. Finally, add 7mol of dopamine hydrochloride, and keep the pH of the above mixture at 5.0-6.0, and stir at room temperature overnight. The mixed solution is then added to a dialysis bag, dialyzed in deionized water for 3 days, and then freeze-dried to finally obtain dopamine-grafted hyaluronic acid.

[0061] (3) Preparation of ultrasonically responsive piezoelectric hydrogels

[0062] Dissolve 30 mg of freeze-dried dopamine-grafted hyaluronic acid obtained in step (2) in 1 ml of deionized water, add 1 mL of 10 mg / mL KNN@PDA, 100 μL of 1 mg / mL horseradish peroxidase (HRP) solution and 5 μL of 30% H2O2, stir evenly and place at 37°C for 5 minutes to obtain an ultrasonically responsive piezoelectric hydrogel.

[0063] The SEM electron microscope image of potassium sodium niobate nanowires (KNN) prepared in step (1) is as follows: Figure 2 As shown, from Figure 2 It can be seen that linear potassium sodium niobate nanowires were successfully synthesized through three-step calcination.

[0064] The SEM electron microscope image of the piezoelectric hydrogel prepared in step (3) is as follows: Figure 3 Specifically, the freeze-dried hydrogel sample was placed in liquid nitrogen for about 20 seconds, fractured in liquid nitrogen, and pasted on the sample table with the fracture surface facing up. The microscopic morphology was observed after gold spraying. Figure 3 It can be seen from the figure that the piezoelectric hydrogel has a porous structure.

[0065] The in vitro degradation performance of the piezoelectric hydrogel was tested. Specifically, the hydrogel sample blocks were placed in a 1 mg / mL type II collagenase solution and shaken at 100 rpm in a 37°C constant temperature water bath shaker. The hydrogel samples were taken out at a fixed time every week and their dry weight was measured. Figure 4 As shown, from Figure 4 It can be seen that the hydrogel prepared in Example 1 has a better degradation rate than hyaluronic acid, indicating that the hydrogel of the present application is easily degradable.

[0066] Example 2

[0067] A three-dimensional sacrificial template, a polylactic acid (PLA) frame (15 mm × 15 mm × 1.5 mm in length × width × thickness), was printed using a commercial 3D printer. The curing agent, polydimethylsiloxane (PDMS), was then mixed with the hydrogel prepared in Example 1 at a weight ratio of 1:10 and poured into the PLA mold. After the hydrogel solidified, the PLA sacrificial template was immersed in dichloromethane to remove the PLA, thereby producing a piezoelectric composite film. Positive and negative electrodes were placed on either side of the piezoelectric composite film to create a power generation device. The output voltage and current of the hydrogel were measured under ultrasound. The specific method is as follows: The ultrasonic excitation device mainly consists of a function generator, a radio frequency power amplifier, and a transducer. The pulse signal programmed by the function generator passes through a 400W power amplifier, providing a higher output power to the ultrasonic transducer, driving the transducer to generate ultrasonic waves. The ultrasonic sound intensity is directly calibrated using a commercial digital ultrasonic sound intensity meter. The function generator inputs a set voltage waveform, which is amplified by a power amplifier and then input into an ultrasonic transducer fixed in a water tank. The ultrasonic power meter is fixed directly in front of the ultrasonic probe, ensuring that the earpiece is aligned with the center of the ultrasonic probe. This allows the corresponding ultrasonic sound intensity to be directly measured. Next, the electrical device is fixed approximately 2 cm away from the center of the ultrasonic transducer, facing the center of the ultrasonic transducer. By adjusting the amplitude of the sine wave output by the function generator, the relationship between the input voltage and the ultrasonic sound intensity can be obtained. Finally, the hydrogel power device is driven at the calibrated ultrasonic sound intensity, and the output voltage of the hydrogel device is measured using an oscilloscope and current amplifier.

[0068] The actual picture of the power generation device prepared in Example 2 is as follows Figure 5 shown.

[0069] The output voltage of the piezoelectric composite film prepared in Example 2 is as follows: Figure 6 As shown, from Figure 6 It can be seen that after adding piezoelectric nanowires, the output of the hydrogel device increased from 5.5V to 18.5V. It can be seen that the introduction of nanowires into the hyaluronic acid three-dimensional network can increase the piezoelectric properties and thus increase the output performance of the hydrogel nanopower generation device.

[0070] In the description of this specification, the reference terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0071] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention.

Claims

1. A power generation device, characterized in that: It includes a positive electrode, a negative electrode and a piezoelectric composite film, wherein the positive electrode and the negative electrode are respectively located on both sides of the piezoelectric composite film, and the piezoelectric composite film is prepared by ultrasonically responsive piezoelectric hydrogel; The ultrasonically responsive piezoelectric hydrogel comprises potassium sodium niobate nanowires whose surfaces are modified with dopamine and hyaluronic acid grafted with dopamine; The mass ratio of the potassium sodium niobate nanowires whose surfaces are modified with dopamine to the dopamine-grafted hyaluronic acid is (2-10):(20-35).

2. The power generating device according to claim 1, characterized in that The preparation method of the potassium sodium niobate nanowires whose surfaces are modified with dopamine comprises: (1) mixing niobium pentoxide, potassium chloride, and potassium carbonate, ball milling the mixture, and then calcining the mixture for the first time to obtain potassium sodium niobate precursor nanowires; then adding nitric acid solution, stirring the mixture, washing the mixture with ultrapure water for multiple times, and drying the mixture; and then calcining the mixture for the second time; grinding and mixing the product after the second calcination with sodium chloride, sodium carbonate, potassium chloride, and potassium carbonate, and then calcining the mixture for the third time to obtain potassium sodium niobate nanomaterials; (2) adding the potassium sodium niobate nanomaterial into a buffer solution and stirring, then adding dopamine hydrochloride and stirring, washing with water, centrifuging and drying to obtain potassium sodium niobate nanowires with dopamine modified surfaces.

3. The power generation device according to claim 2, characterized in that In step (1), the molar ratio of niobium pentoxide, potassium chloride and potassium carbonate is (1-1.5): (10-15): (0.3-1); Optionally, the first calcination temperature is 800-1000° C. and the time is 2-4 hours; Optionally, the second calcination temperature is 500-600° C. and the time is 1-1.5 h; Optionally, the mass ratio of the product after the second calcination, sodium chloride, sodium carbonate, potassium chloride and potassium carbonate is (1-2): (3-4): (0.2-0.5): (3-4): (0.2-0.5); Optionally, the temperature of the third calcination is 800-1000° C., and the time is 5-10 minutes.

4. The power generating device according to claim 1, characterized in that The preparation method of the dopamine-grafted hyaluronic acid comprises: After dissolving 0.8 g to 1.2 g of hyaluronic acid in 125 mL of water, alkali is added to adjust the pH of the hyaluronic acid solution to 5.0 to 6.0, then 7 mol to 8 mol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 7 mol to 8 mol of N-hydroxysuccinimide are added with stirring, and finally dopamine is added and stirred at room temperature for 10 h to 18 h, followed by dialysis to obtain dopamine-grafted hyaluronic acid.

5. The power generating device according to claim 1, characterized in that The method for preparing the ultrasonically responsive piezoelectric hydrogel comprises: The sodium potassium niobate nanowires whose surfaces are modified with dopamine, dopamine-grafted hyaluronic acid, horseradish peroxidase and a hydrogen peroxide solution are mixed, stirred and allowed to stand to obtain an ultrasonically responsive piezoelectric hydrogel.

6. The power generating device according to claim 5, characterized in that The added mass ratio of the potassium sodium niobate nanowires with dopamine-modified surfaces, the dopamine-grafted hyaluronic acid, the horseradish peroxidase, and the hydrogen peroxide solution is (2-10):(20-35):(0.1-0.3):(5-8); Optionally, the concentration of the hydrogen peroxide is 20-30%; Optionally, the standing temperature is 30-40° C., and the standing time is 3-10 minutes.

Images