Piezoelectric hydrogel material for wound healing and preparation method and application thereof

Abstract

The invention belongs to the technical field of medical instruments, and particularly relates to a piezoelectric hydrogel material for wound healing and a preparation method and application thereof. The invention firstly provides a piezoelectric hydrogel material. The piezoelectric hydrogel material is formed by compounding a medical absorbable high-molecular polymer and a piezoelectric polymer material; the medical absorbable high-molecular polymer is a material which contains hydrophilic hydroxyl and can be prepared into a gel matrix. According to the piezoelectric hydrogel provided by the invention, the defects that single hydrogel is amorphous and poor in mechanical property are overcome; and the defects that the piezoelectric property of a single piezoelectric polymer is weak, and the relatively high requirement of a material of tissue engineering on the piezoelectric property is difficult to meet are overcome.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and in particular relates to a piezoelectric hydrogel material for wound healing, a preparation method and an application thereof. Background Art

[0002] Skin wound healing is a complex physiological process, and the whole process is affected by many endogenous and exogenous factors. Wound dressings are an important means of covering the injured skin surface and promoting wound recovery. Traditional wound dressings are mostly natural fibrous materials such as sterile gauze, medical cotton wool, and bandages. These dressings are characterized by soft texture and strong absorption, which can provide a basic physical barrier for the damaged area. However, if the wound cannot be kept moist, this type of dressing is prone to adhesion to the wound surface and even cause infection, which will delay the progress of wound healing. Compared with traditional wound dressings, hydrogels are one of the most promising materials for preparing new dressings. Hydrogels have a variety of shapes and can fully keep the wound moist, thereby providing a moist environment for wound healing and reducing wound pain. However, hydrogels themselves have no adhesion and often require secondary dressings to fix them. In addition, single hydrogel dressings have poor mechanical properties and a long wound healing period.

[0003] Piezoelectric material is a special crystalline material. When subjected to external pressure, a certain voltage will be generated between the two end surfaces of the material, providing a certain electrical stimulation to the wound. Piezoelectric materials include piezoelectric ceramics, piezoelectric polymers, and piezoelectric composite materials. The literature "Application and Design Ideas of Piezoelectric Materials for Repairing Bone Defects" mentioned that no single piezoelectric material has been found to meet the characteristics of piezoelectric materials for tissue engineering. For example, although piezoelectric ceramics have excellent piezoelectric properties, they have the disadvantages of being brittle and difficult to process. Although piezoelectric polymers are flexible and easy to process, their piezoelectric properties are weak. Therefore, the commonly used methods are to combine piezoelectric ceramics with piezoelectric polymers and piezoelectric materials with bioactive materials. However, the two combinations / composite materials mentioned above mainly have the problems of insufficient interface bonding strength, resulting in stress concentration, uncertain biocompatibility and degradation behavior, which in turn makes it difficult for mechanical properties to achieve a good balance between support and flexibility, and even induce immune response or toxicity problems.

[0004] In summary, it is necessary to propose new methods and strategies to supplement the shortcomings of existing technologies. Summary of the invention

[0005] The purpose of the present invention is to provide a piezoelectric hydrogel material for wound healing, a preparation method and an application thereof, so as to partially solve or alleviate the above-mentioned deficiencies in the prior art. The present invention specifically adopts the following technical solutions.

[0006] A first aspect of the present invention is to provide a piezoelectric hydrogel material for wound healing.

[0007] A piezoelectric hydrogel material for wound healing, wherein the piezoelectric hydrogel material for wound healing is composited from a medical absorbable polymer and a piezoelectric polymer material, wherein the proportion of the medical absorbable polymer is not less than that of the piezoelectric polymer material; the piezoelectric polymer material is poly(3-hydroxybutyrate-co-3-hydroxyvalerate); the mass ratio of the medical absorbable polymer to the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) is 1:1, 3:2 or 4:3; the medical absorbable polymer is a material containing hydrophilic hydroxyl groups that can be prepared as a gel matrix.

[0008] Furthermore, the medical absorbable high molecular polymer includes one or more materials selected from the group consisting of polyvinyl alcohol, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol and polyamide.

[0009] The above-listed medical absorbable polymers all have good biocompatibility and degradability, can be safely degraded in the body, and will not cause severe immune responses, and are suitable for wound repair. From the perspective of molecular structure, medical hydrogel materials such as PVA, PLA, PGA, PCL, and PEG all contain easily regulated functional groups and chain structures, allowing these materials to exhibit similar properties. For example, the hydroxyl group (-OH) in PVA gives it good hydrophilicity and water absorption; similarly, PEG is also rich in -OH, providing strong hydrophilicity, making it excellent in moisturizing. PLA, PGA, and PCL have ester bonds (-COO-), which not only help the material to degrade in the body, but also control its mechanical strength and degradation rate by adjusting the molecular weight and crystallinity of the polymer.

[0010] Furthermore, the mass ratio of the medical absorbable high molecular polymer to the poly (3-hydroxybutyrate co3-hydroxyvalerate) includes 3:2 or 4:3.

[0011] Another aspect of the present invention provides a method for preparing the piezoelectric hydrogel material for wound healing.

[0012] A method for preparing a piezoelectric hydrogel material for wound healing comprises the following steps: S01: dissolving a medical absorbable polymer and poly (3-hydroxybutyrate co3-hydroxyvalerate) into a mixed solution of dimethyl sulfoxide and water, and stirring the mixture in a high-temperature oil bath to obtain a hydrogel precursor solution; S02: applying an electric field to the hydrogel precursor solution to perform a polarization treatment, wherein the conditions for the polarization treatment are to treat the hydrogel precursor solution at a temperature of 50-80° C. and a voltage of 5-10 kV, and then keep the solution at the same temperature as the polarization treatment for 0.5-2 h; S03: Freeze the polarized hydrogel solution at -30°C to -10°C, and then thaw at room temperature; the freezing time is 5 to 6 times the thawing time; repeat the freezing-thawing cycle at least 3 times to obtain the piezoelectric hydrogel material for wound healing.

[0013] In the temperature range of 50-80°C, the molecular activity in PVA hydrogel is enhanced, which helps to improve the plasticity and flexibility of the polymer chain, allowing the electric field to more effectively align dipoles and charged groups. In addition, this temperature range is lower than the decomposition temperature of PVA, but high enough to promote the rearrangement process inside the hydrogel, avoiding structural destruction or irreversible damage caused by excessively high temperatures, and helping to maintain the integrity of the material structure.

[0014] Applying a voltage of 5-10kV can provide PVA hydrogels with sufficient electric field strength to achieve effective polarization. Within this voltage range, the electric field can cause the dipole molecules in the hydrogel to reorient in the direction of the electric field, thereby giving the material piezoelectric properties. In addition, choosing the appropriate voltage level is crucial to avoid electrical breakdown of the hydrogel. Too high a voltage may cause dielectric breakdown and damage the sample; while too low a voltage may fail to meet the polarization requirements.

[0015] Furthermore, the volume ratio of the dimethyl sulfoxide to the water is 1:1.

[0016] Furthermore, the temperature of the high temperature oil bath is 80-120° C.; and the stirring time is 5-10 h.

[0017] Furthermore, the polarization treatment conditions are a temperature of 60-80° C. and a voltage of 8-10 kV.

[0018] Furthermore, the polarization treatment time is 10-30 minutes.

[0019] The piezoelectric hydrogel material for wound healing prepared by the above preparation method.

[0020] Application of the above-mentioned piezoelectric hydrogel material for wound healing in the preparation of wound dressings.

[0021] Furthermore, the wound dressing may optionally be in the form of a bandage.

[0022] Furthermore, the wounds include wounds caused by burns, scalds, ruptures, etc.

[0023] Beneficial technical effects: (1) The piezoelectric hydrogel provided by the present invention has extremely simple components, consisting of only two materials: a medical absorbable high molecular polymer and a piezoelectric polymer. The synergistic effect is achieved by optimizing the ratio of the two components, and the composite hydrogel material finally prepared has both good mechanical properties and good piezoelectric properties. Therefore, the piezoelectric hydrogel provided by the present invention overcomes the shortcomings of amorphous single hydrogel and poor mechanical properties; it also overcomes the shortcomings of weak piezoelectric properties of a single piezoelectric polymer, which is difficult to meet the high requirements of piezoelectric properties for materials in tissue engineering.

[0024] (2) The present invention also provides an innovative preparation method, which is to apply an electric field in the middle of the preparation process, which is an in-situ polarization method. This in-situ polarization method has at least the advantage of a more uniform polarization effect compared to conventional post-processing methods. The electric field can cause the molecular chains to be arranged in an orderly manner when the material is solidified or gelled, thereby obtaining better consistency and enhanced piezoelectric properties. In addition, this method simplifies the process flow, reduces the time and cost consumption caused by a separate polarization process, and reduces the risk of damage or deformation to the material caused by post-molding processing. Finally, in-situ polarization can also improve the thermal stability and long-term stability of the material, and by fixing the molecular chain orientation synchronously with the curing process, it reduces the impact of environmental changes on the final material properties. More importantly, the in-situ polarization method allows the polarization parameters to be flexibly adjusted during the synthesis process according to specific needs, so as to achieve precise control of material properties and meet the requirements of specific applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings required for use in the embodiments or the prior art descriptions are briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual scale. Obviously, the drawings described below are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without paying creative labor.

[0026] Figure 1 A schematic diagram of a preparation method of one embodiment of the present invention; Figure 2 The tensile properties of hydrogels with different PVA contents in one embodiment of the present invention are as follows: (a) is the tensile strength of hydrogels with different PVA contents, and (b) is the tensile strength and elongation at break of hydrogels with different PVA contents; Figure 3The tensile properties of hydrogels with different PHBV contents in one embodiment of the present invention are as follows: (a) tensile properties of hydrogels with different PHBV contents, (b) tensile strength and elongation at break of hydrogels with different PHBV contents; Figure 4 The compressive properties of hydrogels with different PVA contents in one embodiment of the present invention are as follows: (a) compressive strength of hydrogels with different PVA contents, (b) compressive stress and compressive strain of hydrogels with different PVA contents; Figure 5 The compressive properties of hydrogels with different PHBV contents in one embodiment of the present invention are as follows: (a) compressive strength of hydrogels with different PHBV contents, (b) compressive stress and compressive strain of hydrogels with different PHBV contents; Figure 6 The swelling results of PVA / PHBV piezoelectric hydrogels with different ratios in deionized water in one embodiment of the present invention; Figure 7 The piezoelectric performance test of PVA / PHBV piezoelectric hydrogels with different ratios in one embodiment of the present invention: (a) PVA15 / PHBV10, (b) PVA15 / PHBV20, (c) PVA10 / PHBV15, (d) PVA20 / PHBV15, (e) PVA15 / PHBV15, (f) bar graph of piezoelectric performance change; Figure 8 A diagram showing the wound healing process of mouse skin in one embodiment of the present invention; Fig. 9 The HE staining results of the back skin wound tissue sections of mice in different piezoelectric hydrogel groups on the 7th day in one of the embodiments of the present invention; Fig.10 The HE staining results of the skin wound tissue sections on the back of mice in different piezoelectric hydrogel groups on the 14th day in one of the embodiments of the present invention (the arrows represent the length of granulation growth); Fig.11 The statistics of collagen fiber content of different piezoelectric hydrogel groups in one embodiment of the present invention on the 7th day and the 14th day respectively; Fig.12 Comparison of the piezoelectric properties of materials using the in-situ poling method and the post-processing poling method. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0028] Herein "and / or" includes any and all combinations of one or more of the associated listed items.

[0029] Herein, "plurality" means two or more than two, ie, it includes two, three, four, five, etc.

[0030] As used in this specification, the term "about" typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value.

[0031] In this specification, some embodiments may be disclosed in a format of being in a range. It should be understood that this description of "being in a range" is only for convenience and brevity, and should not be interpreted as a rigid limitation on the disclosed range. Therefore, the description of the range should be considered to have specifically disclosed all possible sub-ranges and independent numerical values ​​within this range. For example, the description of the range 1-6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within this range, such as 1, 2, 3, 4, 5 and 6. Regardless of the breadth of the range, the above rules apply.

[0032] Name explanation: The term "polarization" as used in the present invention refers to the process in which the charge distribution inside a medium is rearranged under the action of an electric field. Specifically, when a material is subjected to an external electric field, the positive and negative charges in the material will produce relative displacement along the direction of the electric field: positive charges tend to move along the direction of the electric field, while negative charges move in the opposite direction. This redistribution of charge will form a dipole moment inside the material and generate a certain voltage or charge accumulation between its two end faces, which can be maintained for a period of time even after the external electric field is removed.

[0033] The "in situ polarization" mentioned in the present invention refers to the polarization of the hydrogel before it is formed during the synthesis process.

[0034] Example 1 This embodiment provides an example of a piezoelectric hydrogel and a method for preparing the same.

[0035] 1. Experimental Reagents Table 1 Experimental reagents 2. Experimental Equipment Table 2 Experimental equipment 3. Piezoelectric hydrogel This embodiment provides a piezoelectric hydrogel material, which is composed of a medical absorbable polymer and poly (3-hydroxybutyrate co3-hydroxyvalerate) (PHBV). The mass ratio of the medical absorbable polymer to the PHBV is in the range of 2:3 to 3:2. Specifically, as shown in Table 3.

[0036] Table 3 Piezoelectric hydrogel material components 4. Preparation Method S01: Dissolution: PVA and PHBV in different proportions (as shown in Table 3) were dissolved in a mixed solution of 50 mL of dimethyl sulfoxide and 50 mL of water, and heated in an oil bath at 100° C. with stirring for 6 h. The uniformly dissolved solution was then poured into a hydrogel mold.

[0037] S02: Polarization: High voltage polarization was performed at 60°C and 8 kV for 15 min, and maintained at 60°C for 1 h.

[0038] S03: Cyclic freezing: Place the mold in a refrigerator (-20°C) and freeze it for 24 hours. After freezing, place the mold at room temperature (25°C) to thaw for 4 hours. Repeat the freezing-thawing cycle three times to obtain the piezoelectric hydrogel material.

[0039] S04: In order to prevent the hydrogel from losing water at room temperature and affecting its structure and performance, the sealed bag is packaged and stored in a refrigerator. Figure 1 .

[0040] It is understandable that this embodiment is only an example, and other medical absorbable polymer materials for preparing hydrogels, such as one or more of polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol and / or polyamide, are also within the protection scope of the present invention.

[0041] Example 2 This example provides mechanical property, tensile property, compressive property and swelling property tests of the piezoelectric hydrogel prepared in Example 1.

[0042] 1. Mechanical properties Methods: The mechanical properties of hydrogels were tested using an electronic universal testing machine, with a 500 N sensor used for the tensile and loading-unloading tests and a 10 kN sensor used for the compression test. At least three parallel specimens were tested for each hydrogel sample to ensure the validity and reliability of the data.

[0043] 2. Tensile properties Methods: The prepared rectangular hydrogel was cut into rectangular strips with a length of 25 mm, a width of 3 mm, and a thickness of 1 mm to test its tensile properties. A suitable tensile fixture was selected and the sample was fixed on the fixtures at both ends. The distance between the fixtures was measured as the original gauge length. The tensile speed was set to 20 mm / min. After the test was completed, the data was exported and processed and analyzed. The tensile stress ( σ t ) is the force of the sample during stretching ( F ) and the cross-sectional area of ​​the specimen ( S ) ratio. Tensile strength ( σ b ) is the maximum stress of the specimen during the tensile process.

[0044] Specific calculation formula: t = F / S .

[0045] Tensile strain ( ε t ): Length of sample stretched ( l ) and the original length of the sample ( l 0) and the original length ( l 0). Tensile fracture strain ( ε b ) is calculated based on the length of the sample when it breaks, which is the maximum strain. Specific formula: ε t =( l - l 0) / l 0.

[0046] Elastic modulus: The slope of the stress-strain curve in the initial stage (strain: 10~30%).

[0047] Toughness: The integrated area of ​​the stress-strain curve of the hydrogel sample.

[0048] 3. Compression performance Methods: The compression performance was tested using the prepared cylindrical samples (diameter × height: 10 mm × 12 mm), and the compression speed was set at 5 mm / min.

[0049] Compressive stress σ c : The pressure on the sample during compression ( F ) and the sample cross-sectional area ( A ) ratio. Calculation formula: σ c = F / A。

[0050] Compression strain: The height of the sample's compression deformation ( h ) and the original sample height ( h 0).

[0051] Calculation formula: ε c = h / h 0.

[0052] 4. Swelling rate Method: Place the hydrogel sample on an electronic balance to weigh the wet weight. m wet The hydrogel was then allowed to swell in deionized water at 37 °C for 24 h, and the surface water was absorbed using a qualitative filter paper. The swelling weight of the hydrogel was measured at intervals. m swell The swelling rate of the hydrogel was calculated using the following formula: Swelling =( mswell − mwet ) / mwet ×100%.

[0053] Experimental results: The mechanical properties of piezoelectric hydrogels were quantitatively tested by compression and tension experiments. Compared with pure PVA hydrogels, the tensile and compression properties of PVA / PHBV piezoelectric hydrogels were greater than those of pure PVA. Figure 2 As shown in (a), when the PHBV ratio is fixed at 15%, as the PVA content continues to increase, the network structure formed by the hydrogel gradually increases, and the macroscopic performance is the continuous increase in the tensile strength and elongation at break of the hydrogel. When the addition amount of PVA is 20%, its elongation at break is not much different from that when the addition amount is 15%, but the tensile strength is better than that of the experimental group with an addition amount of 15%. Figure 3As shown in (a), when the PVA content is fixed at 15%, as the PHBV content increases, the tensile strength of the hydrogel increases first and then decreases. When the PHBV content increases to 15%, it has the best mechanical strength. The appropriate amount of PHBV particles has a reinforcing effect, which increases the tensile strength of the hydrogel. However, when the amount of PHBV added continues to increase to 20%, too much PHBV agglomerates and forms defects, which reduces the strength of the hydrogel. However, the performance of the composite hydrogel under this ratio is still higher than that of pure PVA.

[0054] In summary, when the ratio of PVA and PHBV is 4:3, the piezoelectric hydrogel has the best mechanical properties, with a tensile strength of 0.9±0.028 MPa and an elongation at break of 570±12.1%.

[0055] Furthermore, the test results of the compressive properties of the piezoelectric hydrogel showed that when the PHBV content was fixed at 15%, as the PVA content continued to increase, the compressive strength of the hydrogel gradually increased. When the ratio of PVA to PHBV was 4:3, the piezoelectric hydrogel had the best mechanical properties, with a compressive stress of 1.6±0.014 MPa and a compressive strain of 60±1.12%. In addition, the compressive strength and strain of the piezoelectric hydrogel were higher than those of the pure PVA hydrogel, see Figure 4 When the amount of PVA added is fixed at 15%, the proportion of PHBV is adjusted, and the results are shown in Figure 5 In general, when the addition amount of PHBV is higher than that of PVA, the compression properties of the composite material decrease.

[0056] Furthermore, the swelling performance test results of the piezoelectric hydrogel showed that within 10 hours of swelling, the hydrogel began to swell, and more and more water molecules were immersed in the hydrogel, and the swelling rate increased to about 300%. Subsequently, the swelling rate showed a slow increase in the last 6 hours, and finally tended to equilibrium, with the highest swelling rate being about 380±7.06%. The PVA / PHBV piezoelectric hydrogel material has a porous structure inside. When water molecules gradually enter the internal voids and occupy these positions, it does not immediately cause a significant change in the overall external volume of the hydrogel. Only when the water molecules completely fill the internal pores and the originally curved polymer chains gradually stretch and release under their action, the volume of the hydrogel will increase significantly. However, the swelling rate of the hydrogel is affected by a combination of multiple factors, including the cross-linking degree and porosity of the internal material, as well as the difference in hydrophilicity and internal and external osmotic pressure, so it is necessary to adjust the ratio to achieve a dynamic balance between the multiple factors. In general, when the amount of PHBV added is higher than that of PVA, the swelling properties of the composite material decreases. Figure 6 .

[0057] Example 3 This example provides a piezoelectric performance test of the piezoelectric hydrogel prepared in Example 1.

[0058] Methods: The piezoelectric properties of hydrogels were tested using a digital source meter. First, a rectangular piezoelectric hydrogel with a length of 25 mm, a width of 5 mm, and a thickness of 2 mm was prepared. The surface was kept as flat as possible to minimize the influence of friction voltage on the piezoelectric properties. The surface moisture of the hydrogel was absorbed with filter paper. The two probes of the digital source meter were inserted into the middle part of the two ends of the piezoelectric hydrogel, and the middle of the hydrogel was pressed to observe whether there was an obvious waveform on the display screen. If there was, it meant that the probe was in good contact with the hydrogel. Then, a cyclic pressure of F=3 N was applied to the hydrogel material, and the voltage change of the hydrogel under pressure on the display screen was continuously observed to evaluate the piezoelectric properties of the hydrogel.

[0059] Experimental results: The piezoelectric properties of PVA / PHBV piezoelectric hydrogels with different ratios are shown in Figure 2. Figure 7 ,like Figure 7 (ac) It can be seen that when PVA is fixed at an addition amount of 15%, as the PHBV content gradually increases, the piezoelectric performance of the piezoelectric hydrogel increases from 0.34±0.019V to about 0.42±0.017V. Under the same external stress, the piezoelectric hydrogel with a high PHBV content has more PHBV inside that can participate in the deformation process, forming more dipole moments, which is macroscopically manifested as an increase in voltage. In addition, with the change of PVA content, the piezoelectric properties of the piezoelectric hydrogel will also change due to the change of the base PVA network skeleton when the hydrogel material is subjected to force. When the PVA content increases, the PVA network structure inside the hydrogel is more, tighter and more complete, which helps to introduce force into the PHBV dipole moment, resulting in an increase in the voltage of the hydrogel material. When the ratio of PVA to PHBV is 4:3, the piezoelectric voltage of the piezoelectric hydrogel reaches 0.49±0.021V.

[0060] Example 4 This example provides animal experiment verification of the piezoelectric hydrogel prepared in Example 1.

[0061] Methods: The skin wound healing experiment was conducted on mice weighing 25 g. Two circular wounds with a diameter of 6 mm were made on the back of each mouse. Nine mice were randomly divided into a blank control group, a PVA / PHBV hydrogel group, and a PVA / PHBV hydrogel pressing group (the ratio of PVA and PHBV was 4:3). A negative blank control group, a positive control group (no pressing of PVA / PHBV hydrogel), and a hydrogel experimental group (pressing of PVA / PHBV hydrogel) were set up. Among them, the negative blank control group did not receive any treatment, the positive control group covered the wound with PVA / PHBV hydrogel, and the experimental group covered and bonded the wound with hydrogel material, and pressed each wound of the mouse for 5 minutes in the first three days to ensure that it played the role of piezoelectric properties. Finally, the wounds of the mice in the experimental group were bandaged with medical film and marked by ear clipping. After the experiment, the mice were put back into the cage, their activities were observed, and equal amounts of food and water were provided at a constant temperature. On the 7th and 14th days after surgery, mice in each group were euthanized, and tissues from the wound sites on the back of the mice were sampled and histologically analyzed. The wound sites on the back of the mice were photographed and recorded on the 3rd, 7th, and 14th days.

[0062] Experimental results: like Figure 8 As shown, the initial wound area of ​​each group was equal, and a small amount of wound secretions were produced. Starting from the 7th day, each group formed a new blood scab at the wound. The wound area of ​​all groups gradually decreased with the increase of the experimental days, the surrounding new skin tissue was covered by epithelial tissue, and no obvious scar tissue was formed. On the 7th day, no complete skin tissue was seen on each wound surface, but the wound area of ​​pressing PVA / PHBV piezoelectric hydrogel was significantly smaller than that of the control group and PVA / PHBV hydrogel group. On the 14th day, the wound pressed by PVA / PHBV piezoelectric hydrogel was basically completely healed, and the healing of the PVA / PHBV piezoelectric hydrogel group was more obvious, while the control group was not completely healed, and there were still obvious wounds exposed on the skin, indicating that it still takes some time to have a significant healing effect.

[0063] Furthermore, Masson staining was used to evaluate the deposition and maturation of collagen in the new tissue. Figure 9-11As shown in the figure, Masson staining showed that on the 7th day, collagen in the control group had not yet formed, and hair follicles existed in large numbers and were in a disordered distribution; collagen in the piezoelectric hydrogel group was arranged more regularly, while collagen deposition in the piezoelectric hydrogel group after pressing was more uniform and arranged regularly. On the 14th day, collagen in the control group and the piezoelectric hydrogel group was in a disordered and loose arrangement, while collagen fibers in the piezoelectric hydrogel group after pressing were parallel to the hair follicles, and collagen deposition was the most orderly and arranged the most uniformly. The results showed that compared with the control group and the non-pressed group, pressing the PVA / PHBV piezoelectric hydrogel group can better promote wound repair. The collagen deposition in Masson-stained sections of wound tissue on the 7th and 14th days was quantitatively analyzed using Image J software. The results showed that the collagen deposition rate of the pressed PVA / PHBV piezoelectric hydrogel was close to 80% on the 7th day, 50% higher than that of the blank control group; on the 14th day, the pressed hydrogel was still much higher than the other two groups. This result further proves the role of piezoelectric hydrogel wound dressing in promoting rapid wound healing.

[0064] Example 5 This embodiment provides a comparative verification of piezoelectric hydrogels prepared by different methods.

[0065] The method of the present invention: S01: Dissolution: PVA and PHBV were dissolved in a mixed solution of 50 mL of dimethyl sulfoxide and 50 mL of water in a mass ratio of 4:3, and heated in an oil bath at 100°C with stirring for 6 h. The uniformly dissolved solution was then poured into a hydrogel mold.

[0066] S02: Polarization: High voltage polarization was performed at 60°C and 8 kV for 15 min, and maintained at 60°C for 1 h.

[0067] S03: Cyclic freezing: Place the mold in a refrigerator (-20°C) and freeze it for 24 hours. After freezing, place the mold at room temperature (25°C) to thaw for 4 hours. Repeat the freezing-thawing cycle three times to obtain the piezoelectric hydrogel material.

[0068] After testing, the piezoelectric voltage of the hydrogel material was 0.49V.

[0069] Control method: S01: Solvent: PVA and PHBV were dissolved in a mixed solution of 50 mL of dimethyl sulfoxide and 50 mL of water in a mass ratio of 4:3, and heated in an oil bath at 100°C with stirring for 6 h. The uniformly dissolved solution was then poured into a hydrogel mold.

[0070] S02: Cyclic freezing: Place the mold in a refrigerator (-20°C) and freeze it for 24 hours. After freezing, place the mold at room temperature (25°C) to thaw for 4 hours. Repeat the freezing-thawing cycle three times to obtain the piezoelectric hydrogel material.

[0071] S03: Polarization: High voltage polarization was performed at 60°C and 8 kV for 15 min.

[0072] After testing, the piezoelectric voltage of the hydrogel material was 0.09V.

[0073] It should be noted that, in this article, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, an element defined by the sentence "comprises a ..." does not exclude the existence of other identical elements in the process, method, article or device including the element.

[0074] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation modes, which are merely illustrative rather than restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are within the protection of the present invention.

Claims

1. A piezoelectric hydrogel material for wound healing, characterized in that: The piezoelectric hydrogel material for wound healing is composited by a medical absorbable polymer and a piezoelectric polymer material, wherein the proportion of the medical absorbable polymer is not less than that of the piezoelectric polymer material; the piezoelectric polymer material is poly(3-hydroxybutyrate-co-3-hydroxyvalerate); the mass ratio of the medical absorbable polymer to the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) includes 1:1, 3:2 or 4:3; the medical absorbable polymer is a material containing hydrophilic hydroxyl groups that can be prepared as a gel matrix.

2. The piezoelectric hydrogel material for wound healing according to claim 1, characterized in that: The medical absorbable high molecular polymer includes one or more materials selected from the group consisting of polyvinyl alcohol, polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol and polyamide.

3. The piezoelectric hydrogel material for wound healing according to claim 1, characterized in that: The mass ratio of the medical absorbable high molecular polymer to the poly (3-hydroxybutyrate co3-hydroxyvalerate) is 3:2 or 4:

3.

4. The method for preparing the piezoelectric hydrogel material for wound healing according to any one of claims 1 to 3, characterized in that: The following steps are involved: S01: dissolving a medical absorbable polymer and poly (3-hydroxybutyrate co3-hydroxyvalerate) into a mixed solution of dimethyl sulfoxide and water, and stirring the mixture in a high-temperature oil bath to obtain a hydrogel precursor solution; S02: applying an electric field to the hydrogel precursor solution to perform a polarization treatment, wherein the conditions for the polarization treatment are to treat the hydrogel precursor solution at a temperature of 50-80° C. and a voltage of 5-10 kV, and then keep the solution at the same temperature as the polarization treatment for 0.5-2 h; S03: Freeze the polarized hydrogel solution at -30°C to -10°C, and then thaw at room temperature; the freezing time is 5 to 6 times the thawing time; repeat the freezing-thawing cycle at least 3 times to obtain the piezoelectric hydrogel material for wound healing.

5. The preparation method according to claim 4, characterized in that: The volume ratio of the dimethyl sulfoxide to the water is 1:

1.

6. The preparation method according to claim 4, characterized in that: The temperature of the high temperature oil bath is 80-120° C.; the stirring time is 5-10 hours.

7. The preparation method according to claim 4, characterized in that: The polarization treatment conditions are a temperature of 60-80° C. and a voltage of 8-10 kV.

8. The preparation method according to claim 4, characterized in that: The polarization treatment time is 10-30 minutes.

9. A piezoelectric hydrogel material for wound healing prepared by the preparation method according to any one of claims 4 to 8.

10. Use of the piezoelectric hydrogel material for wound healing according to any one of claims 1 to 4 or claim 9 in the preparation of wound dressings.

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