A method for preparing an ionic piezoelectric hydrogel for treatment of peripheral nerve injury

Abstract

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

Description

Technical Field

[0001] This invention relates to the field of tissue engineering technology, and in particular to a method for preparing an ionic piezoelectric hydrogel for the treatment of peripheral nerve injury. Background Technology

[0002] Peripheral nerve injury (PNI) is a very common disease in clinical practice. Due to its complexity and the difficulty of repair, the prognosis is often unsatisfactory, leading to long-term negative impacts on patients' quality of life. In recent decades, the rapid development of neural tissue engineering scaffold technology has offered 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 innovation in materials science. Piezoelectric materials exhibit unique advantages in the treatment of peripheral nerve injury. They can respond to minute deformations caused by physiological movements, delivering electrical stimulation to cells or damaged tissues without relying on an external power source. This characteristic allows piezoelectric materials to actively stimulate the physiological electrical microenvironment, providing a dynamic and restorative biological environment for nerve regeneration and repair.

[0003] Currently, most piezoelectric materials are primarily based on organic polymers and inorganic materials. While these materials exhibit good performance in neural repair, their non-biodegradability remains a significant challenge. Non-biodegradable piezoelectric materials require secondary surgery for removal, which not only increases patient suffering but also potentially leads to complications such as infection, limiting their widespread clinical application. Furthermore, traditional electroactive materials, such as conductive metals, piezoelectric ceramics, and energy storage batteries, are inherently rigid and prone to mechanical mismatch when in contact with soft biological tissues, leading to tissue damage. This material-tissue incompatibility further restricts the application of electroactive materials in neural tissue engineering. Summary of the Invention

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

[0005] To achieve the above objectives, the present invention provides the following solution:

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

[0007] The ionic piezoelectric hydrogel was obtained by mixing and reacting a polyvinyl alcohol (PVA) solution and a phytic acid (PA) solution, followed by freeze-thaw reaction.

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

[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 phytic acid solution has a mass fraction of 25 wt%.

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

[0016] Furthermore, the freeze-thaw cycle includes: freezing the object to a -20°C environment and then thawing it at room temperature (25°C).

[0017] The freeze-thaw cycle is repeated 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 includes soaking the sample in water and NaCl solution sequentially after freeze-thaw cycles.

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

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

[0023] In the ion-piezoelectric hydrogel of this invention, the phosphate groups of phytic acid and the hydroxyl groups of polyvinyl alcohol exhibit hydrogen bonding, which improves the mechanical properties of the hydrogel. 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 and chloride ions, thereby greatly enhancing the piezoelectric output of the hydrogel. Glycerin, being hygroscopic, imparts dehydration resistance to the hydrogel, facilitating its preservation. The resulting hydrogel can generate an output voltage of approximately 400mV under the action of an ultrasonic physiotherapy device, promoting the repair of damaged nerves.

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

[0025] The third technical solution of the present invention: the 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 ion-piezoelectric hydrogel prepared by this invention does not involve other circuit components and has a modulus similar to that of tissue, reducing the rejection phenomenon in organisms caused by modulus mismatch. Furthermore, the ion-piezoelectric hydrogel prepared by this invention has good biocompatibility, stability and degradability, and can effectively avoid the rigidity problem of traditional piezoelectric materials, and has the 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 moving ions. The ion 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 excitation of ultrasound, and promote the activity and functional recovery of nerve cells through electrical stimulation, thereby effectively promoting the recovery of damaged nerves.

[0029] Furthermore, the ion-piezoelectric hydrogel prepared by this 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 uses a freeze-cycle method to prepare ion piezoelectric hydrogels, 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, and environmental protection and pollution-free. It is suitable for mass production and wide application.

[0031] (4) The preparation method provided by the present invention is flexible. The modulus range of the hydrogel can be adjusted by controlling the concentration of the raw materials to match the modulus of biological tissues (i.e., to prepare ion piezoelectric hydrogels with adjustable mechanical properties). It can replicate various templates and obtain functional soft materials with different shapes, thicknesses and excellent mechanical properties.

[0032] (5) The ion piezoelectric hydrogel prepared by the present invention can overcome the problem of small inherent migration gap between anions and cations. By utilizing the electrostatic interaction between phytic acid phosphate groups and sodium ions, the movement of sodium ions is restricted, thereby improving the ion piezoelectric output of the hydrogel. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0034] Figure 1 This is a schematic diagram of the molecular structure of polyvinyl alcohol (PVA), phytic acid (PA), and ionic piezoelectric hydrogels.

[0035] Figure 2 These are scanning electron microscope images of the surfaces of the hydrogels prepared in Example 1 and Comparative Example 1;

[0036] Figure 3 EDS analysis chromatogram of the ion-piezoelectric hydrogel prepared in Example 1;

[0037] Figure 4 The figures show the compression test results of piezoelectric hydrogels with different ions. In the figure, A is the stress-strain diagram, B is the compression modulus diagram, C is the compression cycle diagram of the hydrogel prepared in Example 1, and D is the optical photograph of the hydrogel prepared in Example 1 before and after being subjected to a 1kg weight.

[0038] Figure 5 The figures show the piezoelectric test results of different ionic piezoelectric hydrogels. A is the open-circuit voltage graph, B is the short-circuit current graph, C is the open-circuit voltage graph (electrical output frequency is consistent with ultrasonic frequency), D is the impedance graph, E is the IT graph (current-time graph), F is the open-circuit voltage graph of hydrogels with a diameter of 1 cm and different thicknesses prepared using the method of Example 1, G is the open-circuit voltage graph of hydrogels with a diameter of 1 cm and a thickness of 2 mm prepared using the method of Example 1 under different ultrasonic powers, and H is the open-circuit voltage graph of hydrogels with a diameter of 1 cm and a thickness of 2 mm prepared using the method of Example 1 at 0.72 W / cm². 2 Piezoelectric stability test under ultrasonic power;

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

[0040] Figure 7 The image shows the in vivo inflammation test results of the ion-piezoelectric hydrogel prepared in Example 1.

[0041] Figure 8The images show the results of an experiment on sciatic nerve injury in rats using the ion-piezoelectric hydrogel prepared in Example 1. 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 quantitative cAMP level on day 28; D is the cAMP level on day 28; E is the wet weight ratio of the gastrocnemius muscle; F is the footprint and optical photograph of the gastrocnemius muscle; G is the H&E staining image of the gastrocnemius muscle cross-section; H is the Masson staining image of the gastrocnemius muscle cross-section; I is the quantitative measurement of muscle fiber area in the Masson image; J is the TEM image of the longitudinal section of the sciatic nerve; and K is the quantitative measurement of myelin sheath thickness in the TEM image. Detailed Implementation

[0042] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of 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 terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Every smaller range between any stated value or intermediate value within a stated range, and any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0044] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0045] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

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

[0047] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

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

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

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

[0051] Example 1

[0052] A method for preparing an ion-piezoelectric hydrogel for the treatment of peripheral nerve injury:

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

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

[0055] (3) Mix the polyvinyl alcohol solution in step (1) and the phytic acid solution in step (2), and then stir evenly at room temperature at a speed of 400 r / min.

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

[0057] (5) Place the culture dish containing the solution obtained in step (4) in a -20℃ environment for 16 hours to freeze and solidify, and then place it in a room temperature environment for 8 hours to thaw. Repeat the freezing and thawing steps 3 times (i.e., freeze and thaw a total of 3 times).

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

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

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

[0061] Example 2

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

[0063] Example 3

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

[0065] Comparative Example 1

[0066] A method for preparing an ion-piezoelectric hydrogel for the treatment of peripheral nerve injury:

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

[0068] (2) Transfer the polyvinyl alcohol solution obtained in step (1) to a petri dish and let it stand for 3 to 5 minutes to remove air bubbles.

[0069] (3) Place the culture dish containing the solution obtained in step (2) in a -20℃ environment for 16 hours to freeze and solidify, and then place it in a room temperature environment for 8 hours to thaw. Repeat the freezing and thawing steps 3 times (i.e., freeze and thaw a total of 3 times) to obtain an ionic piezoelectric hydrogel (PVA) for the treatment of peripheral nerve injury.

[0070] Comparative Example 2

[0071] A method for preparing an ion-piezoelectric hydrogel for the treatment of peripheral nerve injury:

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

[0073] (2) Transfer the polyvinyl alcohol solution obtained in step (1) to a petri dish and let it stand for 3 to 5 minutes to remove air bubbles.

[0074] (3) Place the culture dish containing the solution obtained in step (2) in a -20℃ environment for 16 hours to freeze and solidify, and then place it in a room temperature environment for 8 hours to thaw. Repeat the freezing and thawing steps 3 times (i.e., freeze and thaw a total of 3 times) to obtain an ion piezoelectric hydrogel (g-PVA) for the treatment of peripheral nerve injury.

[0075] Comparative Example 3

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

[0077] Example of effect 1

[0078] Performance testing

[0079] The hydrogels prepared in Example 1 and Comparative Example 1 were freeze-dried at -50°C for 10 hours, followed by scanning electron microscopy and EDS analysis. The results are shown in the figure. Figure 2 and Figure 3 .

[0080] from Figure 2 and Figure 3 As can be seen, the ion-piezoelectric hydrogel prepared in Example 1 has a rich porous structure, providing channels for ion movement. Furthermore, sodium and chloride ions are uniformly distributed within the hydrogel network.

[0081] Example 2

[0082] (1) Compression tests were performed on different ionic piezoelectric hydrogels (hydrogels prepared in Examples 1-3 and Comparative Examples 1-2), and the results are shown in the figure. Figure 4 , Figure 4 In the diagram, A is the stress-strain diagram, B is the compression modulus diagram, C is the 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 subjected to a 1kg weight.

[0083] from Figure 4 As can be seen, the addition of glycerol improves the mechanical properties of the hydrogel. After adding 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 exhibit good compression cycle stability; for instance, the hydrogel prepared in Example 1 retains 85% of its mechanical properties after 500 compressions.

[0084] (2) Piezoelectricity tests were performed on different ionic piezoelectric hydrogels (hydrogels prepared in Examples 1-3 and Comparative Examples 1-2), and the results are shown in the table below. Figure 5 , Figure 5In the diagram, A represents the open-circuit voltage diagram, B represents the short-circuit current diagram, C represents the open-circuit voltage diagram (the electrical output frequency is consistent with the ultrasonic frequency), D represents the impedance diagram, E represents the IT diagram (current-time diagram), F represents the open-circuit voltage diagrams of hydrogels with a diameter of 1 cm and different thicknesses prepared using the method of Example 1, G represents the open-circuit voltage diagrams of hydrogels with a diameter of 1 cm and a thickness of 2 mm prepared using the method of Example 1 at different ultrasonic powers, and H represents the open-circuit voltage diagrams of hydrogels with a diameter of 1 cm and a thickness of 2 mm prepared using the method of Example 1 at 0.72 W / cm². 2 Piezoelectric stability test under ultrasonic power.

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

[0086] Example 3

[0087] Cell compatibility was tested on piezoelectric hydrogels with different ions, using the following methods:

[0088] a) The materials (hydrogels prepared in Examples 1-3 and Comparative Examples 1-2) were sterilized by cyclic soaking in 75% alcohol and PBS buffer solution for 15 min. Then, the sterilized materials were soaked in cell culture medium and extracted at (37±1)℃ for 24 h to obtain the extract.

[0089] Subsequently, cells that showed good growth after resuscitation were collected and resuspended in the extract, and then processed at a rate of 2×10⁻⁶. 4 Use a pipette to add the liquid to the corresponding well of the plate. Each set of materials has three parallel sets. After completing the above operations, place the 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. Results are shown below. Figure 6 , Figure 6 In the diagram, A is a cell staining image (green fluorescence indicates live cells), B is a quantitative image of live 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 removed at different time points, and the mass of the hydrogel before and after implantation was calculated).

[0091] from Figure 6 As can be seen, the different ionic piezoelectric hydrogels all exhibit good biocompatibility, and the cells can grow normally.

[0092] Example of effect 4

[0093] The ion-piezoelectric hydrogel prepared in Example 1 was subjected to in vivo inflammation testing. The specific method was as follows:

[0094] A 1.5% pentobarbital solution was injected intraperitoneally into rats at a dose of 30 mg / kg to anesthetize them. The rats' 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 according to the method in Example 1) was placed subcutaneously on the back. Tissue samples were collected on days 3 and 7, and H&E staining was performed on the samples to analyze the inflammation. The results are shown in [Figure 1]. Figure 7 .

[0095] from Figure 7 As can be seen from the results, the ion-piezoelectric hydrogel prepared in Example 1 exhibited non-toxicity and safety in vivo for 7 days.

[0096] Example 5

[0097] The ion-piezoelectric hydrogel prepared in Example 1 was used to test sciatic nerve injury in rats. The results are shown in [Figure 1]. Figure 8 , Figure 8 In the figures, 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 quantitative cAMP on day 28, D is the cAMP graph on day 28, E is the wet weight ratio of the gastrocnemius muscle, F is the footprint and optical photograph of the gastrocnemius muscle, G is the H&E staining image of the gastrocnemius muscle cross section, H is the Masson staining image of the gastrocnemius muscle cross section, I is the quantitative muscle fiber area in the Masson image, J is the TEM image of the longitudinal section of the sciatic nerve, and K is the quantitative myelin sheath thickness in the TEM image. From left to right in F, G, H, and J, they represent the sham surgery group, control group, ultrasound group, material group (hydrogel), material + ultrasound group (US + hydrogel), and ex-dermal electrical stimulation group (Ex-electrical).

[0098] The specific testing method is as follows:

[0099] A 1.5% pentobarbital solution was injected intraperitoneally into rats at a dose of 30 mg / kg to anesthetize them. The rats' backs were shaved (5×5 cm area). Under aseptic conditions, the rat skin was incised, and the muscle tissue was carefully dissected to fully expose the sciatic nerve. After gently dissecting the sciatic nerve, a sterile PE60 catheter (commercially available, 0.76 mm outer diameter, 1.22 mm inner diameter, and 2 mm length) was gently looped around the sciatic nerve to simulate nerve compression injury. The surgical incision was sutured in layers. The rats were housed individually until they naturally recovered, and then fed normally for 72 hours. The rats were anesthetized again, and the tissue was dissected along the original surgical incision. The PE60 catheter looped around the sciatic nerve was carefully and completely removed. Partial muscle tissue layers were sutured, and then a hydrogel (g-PVA-PA5 hydrogel prepared using the method in Example 1) was implanted into the nerve injury area. The hydrogel is a disc-shaped structure with a diameter of 10 mm and a thickness of 2 mm. A muscle tissue septum of 5 ± 0.5 mm is maintained between the lower surface of the hydrogel and the episial membrane of the sciatic nerve. After implantation, the surgical incision is closed.

[0100] The experiment was set up with 6 groups: (1) sham surgery group, (2) control group, (3) ultrasound group (US), (4) material group (hydrogel group), (5) material + ultrasound group (US + hydrogel group), and (6) external electrical stimulation group (Ex-electrical).

[0101] In the sham surgery group, after the sciatic nerve was exposed by separating the tissue, the PE60 catheter was not looped and the suture was performed directly.

[0102] The control group had nerve damage but 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) had nerve damage and was treated with ultrasound + hydrogel.

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

[0107] Treatment began on the first day after surgery, with the ultrasonic physiotherapy device providing a power of 0.72 W / cm². 2The operating frequency is 1MHz, the action time is 10 minutes / day, and the treatment cycle is 28 days.

[0108] In the Ex-electrical group, rats were anesthetized, and the electrode clips of the signal generator were attached to the skin of the rat's leg. An AC current output of 300mV at a frequency of 1MHz was applied, and the treatment was repeated every 5 days. The experimental period was 28 days.

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

[0110] from Figure 8 As can be seen from the results, the ion-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 preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for the preparation of ionic piezoelectric hydrogels for the treatment of peripheral nerve injury, characterized by, The method comprises the following steps: The polyvinyl alcohol solution and the phytic acid solution are mixed and reacted, then are frozen and thawed, and then are sequentially soaked in water and a NaCl solution to obtain the ionic piezoelectric hydrogel; The freezing and thawing comprises: freezing molding in an environment at-20℃, and then placing in a room temperature environment for thawing; The freezing and thawing is performed 1-5 times; The solvent in the polyvinyl alcohol solution comprises water and glycerol; The solvent in the phytic acid solution comprises water; The ionic piezoelectric hydrogel promotes recovery of damaged nerves under the action of ultrasonic waves.

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

3. 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 25 wt%; And / or, the volume ratio of the polyvinyl alcohol solution to the phytic acid solution is 10:(1-5).

4. The method of claim 1, wherein, The freezing time is 16 hours; And / or, the thawing time is 8 hours.

5. The preparation method according to claim 1, characterized in that, The soaking time in water and the NaCl solution is 48 hours and 24 hours, respectively.

6. An ionic piezoelectric hydrogel prepared by the preparation method in any one of claims 1-5.

7. Use of the ionic piezoelectric hydrogel in claim 6 in preparation of a material for treatment of peripheral nerve injury.

Images