Preparation method of ionic piezoelectric hydrogel for treating peripheral nerve injury

Abstract

The invention discloses a preparation method of ionic piezoelectric hydrogel for treating peripheral nerve injury, and belongs to the technical field of tissue engineering. The preparation method of the ionic piezoelectric hydrogel for treating the peripheral nerve injury comprises the following steps: mixing a polyvinyl alcohol solution and a phytic acid solution, reacting, and freezing and thawing to obtain the ionic piezoelectric hydrogel. The ionic piezoelectric hydrogel prepared by the method does not involve other circuit elements, has modulus similar to that of tissues, and reduces organism rejection caused by modulus mismatching. And the ionic piezoelectric hydrogel prepared by the method has good biocompatibility, stability and degradability, can effectively avoid the rigidity problem of the traditional piezoelectric material, and has application potential in tissue engineering.

Description

Technical Field

[0001] The present invention relates to the technical field of tissue engineering, and in particular to a method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve damage. Background Art

[0002] Peripheral nerve injury (PNI) is an extremely common disease in clinical practice. Due to the complexity and difficulty of repairing peripheral nerve injuries, its prognosis is often unsatisfactory, which has a long-term negative impact on the patient's quality of life. In recent decades, the rapid development of neural tissue engineering scaffold technology has provided new hope for peripheral nerve regeneration. Research in this field has gradually become a hot topic, especially how to restore the intrinsic electrical excitability of nerve cells through innovations in materials science. Piezoelectric materials have shown unique advantages in the treatment of peripheral nerve injuries. They can respond to tiny deformations caused by physiological movements and can transmit electrical stimulation to cells or damaged tissues without relying on an external power source. This property enables piezoelectric materials to actively stimulate the physiological electrical microenvironment, providing a dynamic and restorative biological environment for nerve regeneration and repair.

[0003] At present, most piezoelectric materials are mainly based on organic polymer materials and inorganic materials. Although these materials have shown good performance in nerve repair, their non-biodegradability remains a problem that needs to be solved urgently. Non-degradable piezoelectric materials need to be removed through a secondary operation, which not only increases the pain of patients, but may also cause complications such as infection, limiting their wide application in clinical practice. In addition, traditional electroactive materials, such as conductive metals, piezoelectric ceramics and energy storage batteries, are prone to mechanical mismatch when in contact with soft biological tissues due to their inherent rigidity, leading to damage to biological tissues. This incompatibility between materials and tissues further limits the application of electroactive materials in neural tissue engineering. Summary of the Invention

[0004] The purpose of the present invention is to provide a method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury, so as to solve the problems existing in the above-mentioned prior art.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention is a method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury, comprising the following steps:

[0007] The polyvinyl alcohol (PVA) solution and the phytic acid (PA) solution are mixed and reacted, and then frozen and thawed to obtain the ionic piezoelectric hydrogel.

[0008] Furthermore, the solvent in the polyvinyl alcohol solution includes water and glycerol;

[0009] The solvent in the phytic acid solution includes water.

[0010] Furthermore, the volume ratio of water to glycerol in the polyvinyl alcohol solution is (5-9): (1-5).

[0011] Furthermore, the volume ratio of water to glycerol in the polyvinyl alcohol solution is 9:1, 8:2, 7:3, 6:4 or 5:5.

[0012] Furthermore, the volume ratio of water to glycerol in the polyvinyl alcohol solution is 6:4.

[0013] Furthermore, the concentration of the polyvinyl alcohol solution is 0.1 g / mL;

[0014] The mass fraction of the phytic acid solution is 25wt%;

[0015] The volume ratio of the polyvinyl alcohol solution to the phytic acid solution is 10:(1-5).

[0016] Furthermore, the freeze-thaw process includes: freezing the formed product in a -20°C environment and then thawing the product in a room temperature (25°C) environment;

[0017] The number of freeze-thaw cycles is 1 to 5 times.

[0018] Furthermore, the freezing time is 16 hours;

[0019] The thawing time is 8 hours.

[0020] Furthermore, the preparation method further comprises soaking in water and NaCl solution in sequence after freeze-thawing.

[0021] Furthermore, the soaking time in water and NaCl solution is 48 hours and 24 hours respectively.

[0022] The purpose of soaking in NaCl solution is to allow the hydrogel to adsorb sodium ions and chloride ions for generating piezoelectric output.

[0023] The ionic piezoelectric hydrogel of the present invention forms hydrogen bonds between the phosphate groups of phytic acid and the hydroxyl groups of polyvinyl alcohol, improving the hydrogel's mechanical properties. The electrostatic interaction between the phosphate groups of phytic acid and sodium ions restricts the movement of sodium ions, resulting in a significant difference in the diffusion coefficients of sodium ions and chloride ions, significantly increasing the hydrogel's piezoelectric output. Glycerol is hygroscopic, imparting dehydration resistance to the hydrogel and facilitating storage. The resulting hydrogel can generate an output voltage of approximately 400 mV when used with an ultrasonic therapy device, promoting the repair of damaged nerves.

[0024] The second technical solution of the present invention: an ionic piezoelectric hydrogel prepared by the above preparation method.

[0025] The third technical solution of the present invention: an application of the above-mentioned ionic piezoelectric hydrogel in the preparation of materials for the treatment of peripheral nerve injury.

[0026] The present invention discloses the following technical effects:

[0027] (1) The ionic piezoelectric hydrogel prepared by the present invention does not involve other circuit components and has a modulus similar to that of tissue, reducing the phenomenon of biological rejection caused by modulus mismatch. In addition, the ionic piezoelectric hydrogel prepared by the present invention has good biocompatibility, stability, and degradability, and can effectively avoid the rigidity problems of traditional piezoelectric materials, showing potential for application in tissue engineering.

[0028] (2) The present invention uses polyvinyl alcohol (PVA) and phytic acid (PA) as solutes, water and glycerol as solvents, and sodium ions and chloride ions as freely mobile ions. The ionic piezoelectric hydrogel prepared by the freeze-cycle method can rely on intermolecular forces to expand the migration gap between sodium ions and chloride ions, generate electrical output under the stimulation of ultrasound, promote the activity and functional recovery of nerve cells through electrical stimulation, and achieve the effect of effectively promoting the recovery of damaged nerves.

[0029] Furthermore, the ionic piezoelectric hydrogel prepared by the present invention has high piezoelectric output capability and the function of promoting the repair of peripheral nerve damage, and has extremely broad application prospects in neural tissue engineering.

[0030] (3) The present invention adopts a freezing-cycling method to prepare ionic piezoelectric hydrogel, which has the advantages of simple preparation process (not involving chemical modification and complex experimental conditions), strong repeatability, easy availability of raw materials, low cost, environmental protection and no pollution, etc. It is suitable for mass production and suitable for wide application.

[0031] (4) The preparation method provided by the present invention is flexible. By adjusting the concentration of the raw materials, the modulus range of the hydrogel can be adjusted to fit the modulus of biological tissue (i.e., an ionic piezoelectric hydrogel with adjustable mechanical properties can be prepared). It can replicate a variety of templates and obtain functional soft materials with different shapes, thicknesses, and excellent mechanical properties.

[0032] (5) The ionic piezoelectric hydrogel prepared by the present invention can overcome the problem of the small inherent migration gap between anions and cations, and utilize the electrostatic interaction between phytic acid phosphate groups and sodium ions to limit the movement of sodium ions and improve the ionic piezoelectric output of the hydrogel. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0034] Figure 1 Schematic diagram of the molecular structure of polyvinyl alcohol (PVA), phytic acid (PA) and ionic piezoelectric hydrogel;

[0035] Figure 2 Surface scanning electron micrographs of the hydrogels prepared in Example 1 and Comparative Example 1;

[0036] Figure 3 This is the EDS analysis diagram of the ionic piezoelectric hydrogel prepared in Example 1;

[0037] Figure 4 Figures 1 and 2 are compression test results of piezoelectric hydrogels with different ions, where A is a stress-strain diagram, B is a compression modulus diagram, C is a compression cycle diagram of the hydrogel prepared in Example 1, and D is an optical photograph of the hydrogel prepared in Example 1 before and after being compressed with a 1 kg weight.

[0038] Figure 5 Figure 1 is a graph showing the piezoelectric test results of different ion piezoelectric hydrogels, wherein A is an open circuit voltage graph, B is a short circuit current graph, C is an open circuit voltage graph (the electrical output frequency is consistent with the ultrasonic frequency), D is an impedance graph, E is an IT graph (current-time graph), F is an open circuit voltage graph of hydrogels with a diameter of 1 cm and different thicknesses prepared by the method of Example 1, G is an open circuit voltage graph of a hydrogel with a diameter of 1 cm and a thickness of 2 mm prepared by the method of Example 1 under different ultrasonic powers, and H is an open circuit voltage graph of a hydrogel with a diameter of 1 cm and a thickness of 2 mm prepared by the method of Example 1 at 0.72 w / cm 2 Piezoelectric stability test under ultrasonic power;

[0039] Figure 6 Figures 2 and 3 show the biocompatibility test results of piezoelectric hydrogels with different ions, where A is a cell staining image (green fluorescence indicates living cells), B is a quantitative image of living cells, and C is a degradation image of g-PVA-PA5 hydrogel in rats.

[0040] Figure 7 This is a graph showing the results of in vivo inflammation testing of the ionic piezoelectric hydrogel prepared in Example 1;

[0041] Figure 8These are graphs showing the results of the sciatic nerve injury experiment on rats using the ionic piezoelectric hydrogel prepared in Example 1, wherein A is a schematic diagram of the animal experiment, B is a statistical graph of the mechanical pain threshold of Von Frey fibers, C is the CAMP quantification on the 28th day, D is the CAMP graph on the 28th day, E is the gastrocnemius muscle wet weight ratio, F is an optical photograph of the footprint and gastrocnemius muscle, G is an H&E staining image of the gastrocnemius muscle cross-section, H is a Masson staining image of the gastrocnemius muscle cross-section, I is the quantification of muscle fiber area in the Masson image, J is a TEM image of the sciatic nerve longitudinal section, and K is the quantification of myelin sheath thickness in the TEM image. DETAILED DESCRIPTION

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0043] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0044] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0045] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0046] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0047] It should be pointed out that the matters not described in detail in the present invention are conventional operating means in this field and are not the focus of the present invention.

[0048] Unless otherwise specified, the experimental reagents and materials used in the examples are commercially available.

[0049] Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art.

[0050] Unless otherwise specified, the room temperature in the examples refers to 25°C.

[0051] Example 1

[0052] A method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury:

[0053] (1) Weigh 1 g of polyvinyl alcohol (polyvinyl alcohol type 1799 (brand: Aladdin), degree of alcoholysis 98-99% (mol / mol)), 6 mL of deionized water, and 4 mL of glycerol, and heat to dissolve (98°C, 8 h) to prepare a polyvinyl alcohol solution with a concentration of 0.1 g / mL.

[0054] (2) Weigh 2.5 mL of phytic acid solution (mass fraction: 50 wt%) and 2.5 mL of deionized water to prepare a phytic acid solution with a mass fraction of 25 wt%.

[0055] (3) The polyvinyl alcohol solution in step (1) and the phytic acid solution in step (2) are blended, and then stirred uniformly at room temperature at a rotation speed of 400 r / min.

[0056] (4) Transfer the solution obtained in step (3) to a culture dish and let it stand for 3 to 5 minutes to remove bubbles.

[0057] (5) The culture dish containing the solution obtained in step (4) was placed in a -20°C environment for 16 hours to freeze-form, and then placed in a room temperature environment for 8 hours to thaw, and the freezing and thawing steps were repeated three times (i.e., a total of three freeze-thaw cycles).

[0058] (6) Soaking the hydrogel obtained in step (5) in deionized water to remove unreacted phytic acid small molecules for 48 hours.

[0059] (7) Soaking the hydrogel obtained in step (6) in physiological saline for 24 hours to obtain an ionic piezoelectric hydrogel (g-PVA-PA5) for treating peripheral nerve injury.

[0060] Figure 1 Schematic diagram of the molecular structure of polyvinyl alcohol (PVA), phytic acid (PA) and ionic piezoelectric hydrogel.

[0061] Example 2

[0062] The same as Example 1, except that step (2) is specifically as follows: 0.5 mL of phytic acid solution (mass fraction of 50 wt%) and 0.5 mL of deionized water are weighed to prepare a phytic acid solution with a mass fraction of 25 wt%; and an ionic piezoelectric hydrogel (g-PVA-PA1) for the treatment of peripheral nerve injury is obtained.

[0063] Example 3

[0064] The same as Example 1, except that step (2) is specifically as follows: 1.5 mL of phytic acid solution (mass fraction of 50 wt%) and 1.5 mL of deionized water are weighed to prepare a phytic acid solution with a mass fraction of 25 wt%; and an ionic piezoelectric hydrogel (g-PVA-PA3) for the treatment of peripheral nerve injury is obtained.

[0065] Comparative Example 1

[0066] A method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury:

[0067] (1) Weigh 1 g of polyvinyl alcohol and 10 mL of deionized water, heat and dissolve (98°C, 8 h) to prepare a polyvinyl alcohol solution with a concentration of 0.1 g / mL.

[0068] (2) The polyvinyl alcohol solution obtained in step (1) was transferred to a culture dish and then allowed to stand for 3 to 5 minutes to remove bubbles.

[0069] (3) The culture dish containing the solution obtained in step (2) is placed in a -20°C environment for 16 hours to freeze-form, and then placed in a room temperature environment for 8 hours to thaw, and the freezing and thawing steps are cycled three times (i.e., a total of three freeze-thaw cycles) to obtain an ionic piezoelectric hydrogel (PVA) for the treatment of peripheral nerve injury.

[0070] Comparative Example 2

[0071] A method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury:

[0072] (1) Weigh 1 g of polyvinyl alcohol, 6 mL of deionized water, and 4 mL of glycerol, heat and dissolve them (98°C, 8 h) to prepare a polyvinyl alcohol solution with a concentration of 0.1 g / mL.

[0073] (2) The polyvinyl alcohol solution obtained in step (1) was transferred to a culture dish and then allowed to stand for 3 to 5 minutes to remove bubbles.

[0074] (3) The culture dish containing the solution obtained in step (2) was placed in a -20°C environment for 16 hours to freeze-form, and then placed in a room temperature environment for 8 hours to thaw, and the freezing and thawing steps were cycled three times (i.e., a total of three freeze-thaw cycles) to obtain an ionic piezoelectric hydrogel (g-PVA) for the treatment of peripheral nerve injury.

[0075] Comparative Example 3

[0076] The same as Example 1, except that the solvent in step (1) is 10 mL of deionized water.

[0077] Effect Example 1

[0078] Performance Testing

[0079] The hydrogels prepared in Example 1 and Comparative Example 1 were freeze-dried at -50°C for 10 h, and then subjected to scanning electron microscopy and EDS analysis. Figure 2 and Figure 3 .

[0080] from Figure 2 and Figure 3 As can be seen from the figure, the ionic piezoelectric hydrogel prepared in Example 1 has a rich porous structure, which provides channels for the movement of ions. In addition, sodium ions and chloride ions are evenly distributed in the hydrogel network.

[0081] Effect Example 2

[0082] (1) Compression tests were performed on different ionic piezoelectric hydrogels (hydrogels prepared in Examples 1 to 3 and Comparative Examples 1 to 2). The results are shown in Table 1. Figure 4 , Figure 4 A is a stress-strain diagram, B is a compression modulus diagram, C is a compression cycle diagram of the hydrogel prepared in Example 1, and D is an optical photograph of the hydrogel prepared in Example 1 before and after being compressed with a 1 kg weight.

[0083] from Figure 4 As can be seen in the figure, the addition of glycerol improves the mechanical properties of the hydrogel. After adding the phytic acid solution, the modulus of the hydrogel is approximately 110 kPa, which is similar to the modulus of muscle tissue (approximately 100 kPa). Furthermore, the hydrogels prepared in the examples all exhibited good compression cycle stability. For example, the hydrogel prepared in Example 1 retained 85% of its mechanical properties after 500 compression cycles.

[0084] (2) The piezoelectricity test was performed on the piezoelectric hydrogels with different ions (the hydrogels prepared in Examples 1 to 3 and Comparative Examples 1 to 2). The results are shown in Figure 5 , Figure 5A is the open circuit voltage diagram, B is the short circuit current diagram, C is the open circuit voltage diagram (the electrical output frequency is consistent with the ultrasonic frequency), D is the impedance diagram, E is the IT diagram (current-time diagram), F is the open circuit voltage diagram of the hydrogel with a diameter of 1 cm and different thicknesses prepared by the method of Example 1, G is the open circuit voltage diagram of the hydrogel with a diameter of 1 cm and a thickness of 2 mm prepared by the method of Example 1 under different ultrasonic powers, H is the open circuit voltage diagram of the hydrogel with a diameter of 1 cm and a thickness of 2 mm prepared by the method of Example 1 at 0.72 w / cm 2 Piezoelectric stability test under ultrasonic power.

[0085] from Figure 5 As can be seen in the graph, hydrogels with different amounts of phytic acid exhibit different piezoelectric outputs. The hydrogel containing 5 mL of phytic acid solution (Example 1) exhibits the best piezoelectric output, ion mobility, and electrical output stability (Figure H), with an open-circuit voltage of approximately 400 mV and a short-circuit current of approximately 3 μA. Furthermore, Figures F and G show that both hydrogel thickness and ultrasonic power affect piezoelectric output.

[0086] Effect Example 3

[0087] The cell compatibility of different ion piezoelectric hydrogels was tested respectively. The specific method is as follows:

[0088] a) The material (hydrogels prepared in Examples 1 to 3 and Comparative Examples 1 to 2) was sterilized by immersing in a 75% alcohol and PBS buffer solution for 15 minutes in a cycle. The sterilized material was then immersed in a cell culture medium and extracted at (37±1)°C for 24 hours to obtain an extract.

[0089] Then, the cells that grew well after recovery were collected and resuspended in the extract solution. 4 Use a pipette to add the corresponding wells of the plate. Each group of materials has three parallel groups. After completing the above operations, place the well plate in a cell culture incubator (37°C, 5% CO2).

[0090] b) After culturing for 1 and 3 days, observe the cell number and morphology and perform CCK-8 assay. The results are shown in Figure 6 , Figure 6 In the figure, A is a cell staining image (green fluorescence indicates living cells), B is a quantitative image of living cells, and C is a degradation image of g-PVA-PA5 hydrogel in rats (the hydrogel prepared in Example 1 was implanted into rats, and the hydrogel was taken out at different time points, and the mass of the hydrogel before and after implantation was calculated).

[0091] from Figure 6 It can be seen that different ion piezoelectric hydrogels all show good biocompatibility and cells can grow normally.

[0092] Effect Example 4

[0093] The ionic piezoelectric hydrogel prepared in Example 1 was subjected to an in vivo inflammation test, and the specific method was as follows:

[0094] A 1.5% pentobarbital solution was injected intraperitoneally into rats at a dose of 30 mg / kg. The rats were anesthetized and their backs were shaved (the shaved area was 5×5 cm). Under aseptic conditions, the rat skin was incised and the prepared hydrogel (a cylindrical hydrogel with a diameter of 1 cm and a thickness of 2 mm prepared by the method of Example 1) was placed subcutaneously on the back. Samples were collected on the 3rd and 7th days, and the sample tissues were stained with H&E to analyze the inflammatory status. The results are shown in FIG. Figure 7 .

[0095] from Figure 7 It can be seen that the ionic piezoelectric hydrogel prepared in Example 1 showed non-toxicity and safety in vivo for 7 days.

[0096] Effect Example 5

[0097] The ionic piezoelectric hydrogel prepared in Example 1 was used to conduct a rat sciatic nerve injury experiment. The results are shown in Figure 8 , Figure 8 A is a schematic diagram of the animal experiment, B is a statistical graph of the mechanical pain threshold of Von Frey fibers, C is the CAMP quantification on day 28, D is a CAMP graph on day 28, E is the wet weight ratio of the gastrocnemius muscle, F is a footprint and optical photograph of the gastrocnemius muscle, G is an H&E staining image of a gastrocnemius muscle cross section, H is a Masson staining image of a gastrocnemius muscle cross section, I is the quantification of muscle fiber area in the Masson image, J is a TEM image of a longitudinal section of the sciatic nerve, and K is the quantification of myelin sheath thickness in the TEM image. Figures F, G, H, and J show, from left to right, the sham group (sham), control group (control), ultrasound group (US), material group (hydrogel), material + ultrasound group (US + hydrogel), and epidermal electrical stimulation group (Ex-electrical).

[0098] The specific test methods are as follows:

[0099] By the dosage of 30mg / kg, 1.5% pentobarbital solution is injected into rats by intraperitoneal injection, anesthetized rats, and the rat backs are shaved (the shaved area is 5×5cm). Under aseptic operation conditions, the rat skin is incised, the muscle tissue is carefully separated, and the sciatic nerve is fully exposed. After gently separating the sciatic nerve, a sterile PE60 catheter (commercially available, with an outer diameter of 0.76mm, an inner diameter of 1.22mm, and a length of 2mm) is selected and gently looped around the sciatic nerve to simulate nerve compression injury. The surgical incision is sutured in layers. The rats are raised in a single cage, treated to wake up naturally, and then routinely raised for 72 hours. Once again, the rats are anesthetized, and along the original surgical incision, tissue is separated, and the PE60 catheter looped around the sciatic nerve is carefully and completely removed. The partial muscle tissue layer is sutured, and then, a hydrogel (g-PVA-PA5 hydrogel prepared by the method of Example 1) is implanted in the nerve injury area. The hydrogel is a disc-shaped structure with a diameter of 10 mm and a thickness of 2 mm. A 5 ± 0.5 mm gap of muscle tissue is maintained between the lower surface of the hydrogel and the epithelium of the sciatic nerve. After implantation, the surgical incision is closed.

[0100] The whole experiment was divided into 6 groups: (1) sham operation group (sham), (2) control group (control), (3) ultrasound group (US), (4) material group (hydrogel group), (5) material + ultrasound group (US + hydrogel group), and (6) extracutaneous electrical stimulation group (Ex-electrical).

[0101] In the sham group, after the sciatic nerve was seen after tissue separation, the PE60 catheter was not trapped and the nerve was sutured directly;

[0102] The control group (control) had nerve damage and received no treatment;

[0103] The ultrasound group (US) had nerve damage and underwent ultrasound treatment;

[0104] The material group (hydrogel group) had nerve damage and was treated with hydrogel;

[0105] The material + ultrasound group (US+hydrogel group) had nerve damage and was treated with ultrasound + hydrogel;

[0106] The extracutaneous electrical stimulation group (Ex-electrical) had nerve damage and was treated with extracutaneous electrical stimulation.

[0107] Treatment started on the first day after surgery, and the therapeutic power of the ultrasonic therapy device was 0.72W / cm 2, the operating frequency is 1MHZ, the action time is 10 minutes / day, and the treatment cycle is 28 days.

[0108] In the Ex-electrical group, after anesthetizing the rats, the electrode clip of the signal generator was clamped on the skin of the rat's leg, and a 300mV alternating current output at a frequency of 1MHz was applied. Treatment was performed every 5 days for a total of 28 days.

[0109] The therapeutic effect was measured after 28 days of treatment.

[0110] from Figure 8 It can be seen that the ionic piezoelectric hydrogel prepared in Example 1 can effectively promote the repair and regeneration of sciatic nerve injury in rats, relieve neuropathic pain, enhance electrophysiological function, and promote muscle recovery.

[0111] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A method for preparing an ionic piezoelectric hydrogel for treating peripheral nerve injury, characterized in that: The following steps are involved: The polyvinyl alcohol solution and the phytic acid solution are mixed and reacted, and then frozen and thawed to obtain the ionic piezoelectric hydrogel.

2. The preparation method according to claim 1, characterized in that The solvent in the polyvinyl alcohol solution includes water and glycerol; The solvent in the phytic acid solution includes water.

3. The preparation method according to claim 2, characterized in that The volume ratio of water to glycerol in the polyvinyl alcohol solution is (5-9):(1-5).

4. The preparation method according to claim 1, characterized in that The concentration of the polyvinyl alcohol solution is 0.1 g / mL; And / or, the mass fraction of the phytic acid solution is 25wt%; And / or, the volume ratio of the polyvinyl alcohol solution to the phytic acid solution is 10:(1-5).

5. The preparation method according to claim 1, characterized in that The freeze-thaw method includes: freezing the formed product in a -20°C environment and then thawing the product in a room temperature environment; And / or, the number of freeze-thaw cycles is 1 to 5 times.

6. The preparation method according to claim 5, characterized in that The freezing time is 16 hours; And / or, the thawing time is 8 hours.

7. The preparation method according to claim 1, characterized in that It also includes soaking in water and NaCl solution sequentially after freeze-thaw.

8. The preparation method according to claim 7, characterized in that The soaking time in water and NaCl solution is 48 hours and 24 hours respectively.

9. An ionic piezoelectric hydrogel prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the ionic piezoelectric hydrogel according to claim 9 in preparing a material for treating peripheral nerve injury.

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