CN109675095B

CN109675095B - Polyvinyl alcohol hydrogel and preparation method and application thereof

Info

Publication number: CN109675095B
Application number: CN201811637673.2A
Authority: CN
Inventors: 刘玉; 蓝咏; 马春铭; 陈泰瀛
Original assignee: Guangzhou Chuangseed Biomaterials Co ltd
Current assignee: Guangzhou Chuangseed Biomaterials Co ltd
Priority date: 2018-12-29
Filing date: 2018-12-29
Publication date: 2021-07-20
Anticipated expiration: 2038-12-29
Also published as: CN109675095A

Abstract

The invention relates to a polyvinyl alcohol hydrogel and a preparation method and application thereof, belonging to the technical field of polymer hydrogels. Dripping the rubescensin into a sodium alginate microsphere solution, and treating to obtain a rubescensin/sodium alginate microsphere compound; preparing a polyethyleneimine derivative carrier for loading micro RNA through EDC/NHS activation reaction; and finally, uniformly mixing the rubescensin/sodium alginate microsphere compound, the micro RNA/polyethyleneimine derivative carrier and a polyvinyl alcohol solution, and repeatedly freezing and thawing to form the hydrogel material. The hydrogel loaded with the rubescensin/sodium alginate microsphere compound and the micro RNA/polyethyleneimine derivative carrier has the functions of drug slow release and micro RNA regulation, can improve the drug availability of the rubescensin, has the gene treatment effect, and can be applied to skin wound dressings.

Description

Polyvinyl alcohol hydrogel and preparation method and application thereof

Technical Field

The invention relates to a polyvinyl alcohol hydrogel and a preparation method and application thereof, belonging to the technical field of polymer hydrogels.

Background

The skin is located on the surface of the human body and is one of the largest, most important organs of the human body. Due to the long-term large area of skin exposure to the external environment, the skin can be damaged from time to time. When the wound is serious, such as burn, severe cold injury, mechanical wound, ulcer caused by chronic diseases and the like, the pain is brought to the patient, and even the death is caused. Compared with the traditional dressing, the development and preparation of the novel dressing with the effect of promoting healing are very necessary.

Polyvinyl alcohol (PVA) is a long-chain water-soluble high polymer obtained by hydrolyzing polyvinyl ester, is nontoxic and tasteless, has no irritation to skin, does not cause skin allergy, has good film forming property and adhesive force, and can form hydrogel with good biocompatibility under certain conditions.

The rubescensin is an active diterpenoid compound separated and purified from rabdosia rubescens, and researches show that the rubescensin has the effects of resisting bacteria, diminishing inflammation, easing pain, resisting tumors and the like, and has been widely concerned in the field of biomedicine. However, the poor water solubility of oridonin itself severely affects its efficacy. In order to expand the clinical application of rubescensin and improve the drug utilization rate, the research and the preparation of a novel drug carrier are very important.

The sodium alginate is natural biological macromolecule sodium salt extracted from natural brown algae, and has no toxicity to cells and good biocompatibility. The microspheres prepared from sodium alginate are widely applied to the field of biological medicine.

Polyethyleneimine (PEI) has become a gene delivery vector with the most research value and application prospect in the field of non-viral gene vectors. However, pure polyethyleneimine still has many defects, such as relatively high cytotoxicity, non-degradable polymer and the like. Thus. The polyethyleneimine is used as a parent structure, is further modified to overcome the defects, and the synthesized polyethyleneimine derivative is used for a carrier of micro RNA, and is a novel gene carrier material with development potential.

microRNA (microRNA, miR) is a non-coding single-stranded RNA with the length of about 22nt discovered in recent years, can silence the gene expression of the transcribed level so as to play a regulating function, and miR almost participates in all biological regulation and control processes in vivo and can realize gene therapy by matching with a gene vector.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a polyvinyl alcohol hydrogel and a preparation method and application thereof.

In order to achieve the purpose, the invention adopts the technical scheme that: a preparation method of polyvinyl alcohol hydrogel comprises the following steps:

(1) preparing a polyvinyl alcohol aqueous solution: adding polyvinyl alcohol into deionized water, stirring and dissolving to obtain a polyvinyl alcohol aqueous solution;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: adding the rubescensin into the sodium alginate microsphere solution, and freeze-drying for later use;

(3) preparing a polyethyleneimine derivative carrier: dripping polyethyleneimine into a hyaluronic acid solution to obtain a polyethyleneimine derivative carrier;

(4) preparing a miR-29A/polyethyleneimine derivative loaded carrier: dripping the miR-29A solution into the polyethyleneimine derivative carrier obtained in the step (3), and freezing and storing;

(5) preparation of polyvinyl alcohol hydrogel: and (3) mixing the components obtained in the step (1), the step (2) and the step (4) to obtain the polyvinyl alcohol hydrogel.

According to the preparation method, the rubescensin/sodium alginate microsphere compound and the micro RNA/polyethyleneimine derivative carrier are loaded into the polyvinyl alcohol hydrogel material together, so that the effects of drug slow release and gene therapy are achieved, and the research and application of the novel dressing are promoted.

In the preferred embodiment of the preparation method of the polyvinyl alcohol hydrogel, in the step (1), the mass concentration of the polyvinyl alcohol aqueous solution is 5-20%, the dissolving temperature is 80-90 ℃, and the stirring speed is 300-500 r/min.

As a preferred embodiment of the method for preparing a polyvinyl alcohol hydrogel, in the step (2), the method for preparing the sodium alginate microspheres comprises: mixing an emulsifier and vegetable oil to obtain a mixed solution, stirring at normal temperature, dropwise adding a sodium alginate aqueous solution into the mixed solution, continuously stirring at normal temperature, adding a calcium chloride solution, stirring overnight, respectively centrifugally washing with isopropanol and deionized water for three times, and freeze-drying to obtain the sodium alginate microspheres.

As a preferred embodiment of the preparation method of the polyvinyl alcohol hydrogel, in the step (2), the concentration of the sodium alginate microsphere solution is 5-10 mg/mL, 0.5-2 mg of oridonin is added into each milliliter of the sodium alginate microsphere solution, the freeze-drying temperature is-60 ℃, and the freeze-drying time is 24 hours.

As a preferred embodiment of the method for preparing a polyvinyl alcohol hydrogel according to the present invention, in the step (3), the method for preparing a polyethyleneimine derivative carrier comprises: deionized water is used as a solvent, a hyaluronic acid solution with the mass fraction of 0.5-2% is prepared, 0.1-0.5 g of 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDC), 0.2-1 g N-hydroxysuccinimide (NHS) and 1-5 g of polyethyleneimine are added into each gram of hyaluronic acid, EDC/NHS activation reaction is carried out, stirring is carried out at normal temperature overnight, dialysis is carried out for three days by using a dialysis bag with the molecular weight cutoff of 10K, water is changed for 2-3 times each day, and finally freeze drying is carried out for standby, wherein the freeze drying temperature is-60 ℃, and the freeze drying time is 24 hours, so that the polyethyleneimine derivative carrier is obtained.

As a preferable embodiment of the preparation method of the polyvinyl alcohol hydrogel, in the step (4), the dosage of the miR-29A is 50-100 ng of miR-29A added to each mg of the polyethyleneimine derivative carrier.

The miR-29A is a single-chain micromolecule RNAs which are composed of nucleotides, are endogenous, non-coding and have a regulation function on the expression of protein molecules, and researches show that the miR has an important regulation function on angiogenesis-related transcription factors and signal molecules and is expected to be applied to skin repair.

As a preferred embodiment of the method for producing a polyvinyl alcohol hydrogel according to the present invention, in the step (5), the method for producing a polyvinyl alcohol hydrogel comprises: mixing the components obtained in the steps (1), (2) and (4) in equal volume, pouring into a mold, and refrigerating at-20 ℃ overnight.

In a second aspect, the present invention provides a polyvinyl alcohol hydrogel produced according to the above-described production method.

In a third aspect, the present invention provides the use of a polyvinyl alcohol hydrogel as described above in the manufacture of a dressing for the treatment of a skin wound.

Compared with the prior art, the invention has the beneficial effects that: the hydrogel loaded with the rubescensin/sodium alginate microsphere compound and the micro RNA/polyethyleneimine derivative carrier has the functions of drug slow release and micro RNA regulation, can improve the drug availability of the rubescensin, has the gene treatment effect, and can be applied to skin wound dressings.

Drawings

FIG. 1 is a scanning electron microscope image of sodium alginate microspheres of example 1.

FIG. 2 is a nuclear magnetic diagram of a polyethyleneimine derivative carrier according to example 1.

FIG. 3 is a scanning electron micrograph of the hydrogel material of example 1.

FIG. 4 is a drug release profile of the hydrogel material of example 1.

FIG. 5 is a scanning electron micrograph of the hydrogel material of example 2.

FIG. 6 is a scanning electron micrograph of the hydrogel material of example 3.

FIG. 7 is a sustained release diagram of the hydrogel material drug of example 4.

FIG. 8 is a sustained release diagram of the hydrogel material drug of example 5.

Detailed Description

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments.

The test methods adopted in the embodiments of the present invention are all conventional methods unless otherwise specified; the materials, reagents and the like used are commercially available unless otherwise specified.

Example 1

A preparation method of polyvinyl alcohol hydrogel comprises the following steps:

(1) preparing a polyvinyl alcohol aqueous solution: adding 10g of polyvinyl alcohol into 100mL of deionized water, stirring at 90 ℃ until the polyvinyl alcohol is dissolved to obtain a polyvinyl alcohol aqueous solution, and storing for later use;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: mixing 1mL of Tween 80 and 100mL of olive oil, stirring at the normal temperature of 800r/min for 1h, dropwise adding 20mL of sodium alginate water solution with the mass concentration of 2% into the olive oil, continuously stirring at the normal temperature for 1h, finally adding a calcium chloride solution with the mass concentration of 2.5% and 50mg of rubescensin, and stirring overnight; centrifuging and washing the solution with isopropanol and deionized water for three times respectively, wherein the centrifugation speed is 10000r/min, the centrifugation time is 15min each time, and finally, freeze-drying at-60 ℃ for 24h to obtain the oridonin/sodium alginate microsphere loaded compound; FIG. 1 is a scanning electron microscope image of sodium alginate microspheres, and as can be seen from FIG. 1, the prepared sodium alginate microsphere composite has a diameter of about 40 μm and can be used for loading drugs;

(3) preparing a polyethyleneimine derivative carrier: dissolving 0.5g of hyaluronic acid in 100mL of deionized water, adding 0.2g of EDC, 0.4g of NHS and 2g of polyethyleneimine, stirring at normal temperature overnight, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water twice a day, and finally freeze-drying for later use, wherein the freeze-drying condition is freeze-drying for 24 hours at-60 ℃; FIG. 2 is a nuclear magnetic diagram of a polyethyleneimine derivative carrier, and as can be seen from FIG. 2, the product HAs characteristic peaks of both Polyethyleneimine (PEI) and Hyaluronic Acid (HA), so that it can be demonstrated that the polyethyleneimine derivative carrier for loading micro RNA HAs been successfully synthesized;

(4) preparing a mir-29A/polyethyleneimine derivative-loaded carrier: dripping 5 mu L of mir-29A solution with the concentration of 20 mu mol/L into 1mL of the polyethyleneimine derivative carrier obtained in the step (3) to obtain a mir-29A/polyethyleneimine derivative-loaded carrier, and freezing and storing at the temperature of-20 ℃;

(5) preparing a hydrogel material: and (3) taking 1mL of the components obtained in the steps (1), (2) and (4), uniformly mixing at normal temperature, filling into a mold, and placing in a refrigerator at the temperature of-20 ℃ for overnight cooling to obtain the polyvinyl alcohol hydrogel.

FIG. 3 is a scanning electron microscope image of the hydrogel material of this example, and it can be seen from FIG. 3 that the hydrogel prepared in this example has a smooth porous structure, which is a typical hydrogel structure.

The hydrogel prepared in this example was subjected to a drug release test, fig. 4 is a drug release diagram of the hydrogel material, and it can be seen from fig. 4 that the drug is rapidly released in the first 10 hours, the release rate is about 50%, and then the rate is slowed down, and after 120 hours, the drug release rate reaches about 90% of the maximum.

When the hydrogel prepared in this example is used for skin wound repair, as can be seen from table 1, the hydrogel of the control group (containing no microrna) and the hydrogel of the experimental group (containing microrna in this example) have a certain difference in treatment effect within the same time, and after 14 days, the wound diameter of the experimental group is about half of that of the control group, so that the hydrogel of the present invention can be seen to have gene treatment effect.

TABLE 1

Time	Control group	Experimental group
			Day 1	10mm	10mm
Day 3	8mm	7mm
			Day 7	6mm	4mm
Day 14	3mm	1.5mm

Example 2

A preparation method of a polyvinyl alcohol hydrogel material comprises the following steps:

(1) preparing a polyvinyl alcohol aqueous solution: adding 15g of polyvinyl alcohol into 100mL of deionized water, stirring at 90 ℃ until the polyvinyl alcohol is dissolved to obtain a polyvinyl alcohol aqueous solution, and storing for later use;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: mixing 1mL of Tween 80 and 100mL of olive oil, stirring at the normal temperature of 800r/min for 1h, dropwise adding 20mL of sodium alginate water solution with the mass concentration of 2% into the olive oil, continuously stirring at the normal temperature for 1h, finally adding a calcium chloride solution with the mass concentration of 2.5% and 100mg of rubescensin, and stirring overnight; centrifuging and washing the solution with isopropanol and deionized water for three times respectively, wherein the centrifugation speed is 10000r/min, the centrifugation time is 15min each time, and finally, freeze-drying at-60 ℃ for 24h to obtain the oridonin/sodium alginate microsphere loaded compound;

(3) preparing a polyethyleneimine derivative carrier: dissolving 1g of hyaluronic acid in 100mL of deionized water, adding 0.4g of EDC, 0.8g of NHS and 4g of ethylene imine, stirring at normal temperature overnight, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water for two to three times every day, and finally freeze-drying for later use, wherein the freeze-drying condition is freeze-drying for 24 hours at-60 ℃;

(5) preparing a hydrogel material: and (3) taking 1mL of the components obtained in the steps (1), (2) and (4), uniformly mixing at normal temperature, filling into a mold, and placing in a refrigerator at the temperature of-20 ℃ for overnight cooling to prepare the polyvinyl alcohol hydrogel.

FIG. 5 is a scanning electron microscope image of the hydrogel material of this example, and it can be seen from FIG. 5 that the hydrogel prepared in this example has a smooth porous structure, which is a typical hydrogel structure.

Example 3

(1) preparing a polyvinyl alcohol aqueous solution: adding 20g of polyvinyl alcohol into 100mL of deionized water, stirring at 90 ℃ until the polyvinyl alcohol is dissolved to obtain a polyvinyl alcohol aqueous solution, and storing for later use;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: mixing 1mL of Tween 80 and 100mL of olive oil, stirring at the normal temperature of 800r/min for 1h, dropwise adding 20mL of sodium alginate water solution with the mass concentration of 3% into the olive oil, continuously stirring at the normal temperature for 1h, finally adding a calcium chloride solution with the mass concentration of 5% and 100mg of rubescensin, and stirring overnight; centrifuging and washing the solution with isopropanol and deionized water for three times respectively, wherein the centrifugation speed is 10000r/min, the centrifugation time is 15min each time, and finally, freeze-drying at-60 ℃ for 24h to obtain the oridonin/sodium alginate microsphere loaded compound;

(3) preparing a polyethyleneimine derivative carrier: dissolving 1g of hyaluronic acid in 100mL of deionized water, adding 0.4g of EDC, 0.8g of NHS and 4g of polyethyleneimine, stirring at normal temperature overnight, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water for two to three times every day, and finally freeze-drying for later use, wherein the freeze-drying condition is freeze-drying for 24 hours at-60 ℃;

(4) preparing a mir-29A/polyethyleneimine derivative-loaded carrier: dripping 8 mu L of mir-29A solution with the concentration of 20 mu mol/L into 1mL of the polyethyleneimine derivative carrier obtained in the step (3) to obtain a mir-29A/polyethyleneimine derivative-loaded carrier, and freezing and storing at the temperature of-20 ℃;

FIG. 6 is a scanning electron microscope image of the hydrogel material of this example, and it can be seen from FIG. 6 that the hydrogel prepared in this example has a smooth porous structure, which is a typical hydrogel structure.

Example 4

(1) preparing a polyvinyl alcohol aqueous solution: adding polyvinyl alcohol into deionized water, stirring and dissolving to obtain a polyvinyl alcohol aqueous solution, wherein the mass concentration of the polyvinyl alcohol aqueous solution is 5%, the dissolving temperature is 80 ℃, and the stirring speed is 300 r/min;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: adding the rubescensin into the sodium alginate microsphere solution, and freeze-drying for later use; the preparation method of the sodium alginate microspheres comprises the following steps: mixing tween 80 and olive oil to obtain a mixed solution, stirring at normal temperature, dropwise adding a sodium alginate aqueous solution into the mixed solution, continuously stirring at normal temperature, adding a calcium chloride solution, stirring overnight, respectively centrifuging and washing with isopropanol and deionized water for three times, and freeze-drying to obtain sodium alginate microspheres; the concentration of the sodium alginate microsphere solution is 5mg/mL, 0.5mg of rubescensin is added into each milliliter of the sodium alginate microsphere solution, the freeze-drying temperature is-60 ℃, and the freeze-drying time is 24 hours;

(3) preparing a polyethyleneimine derivative carrier: preparing 0.5 mass percent hyaluronic acid solution by taking deionized water as a solvent, adding 0.1g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, 0.2g N-hydroxysuccinimide and 1g of polyethyleneimine into each gram of hyaluronic acid, stirring at normal temperature overnight, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water for 2 times every day, and finally freeze-drying for later use at the temperature of-60 ℃ for 24 hours to obtain a polyethyleneimine derivative carrier;

(4) preparing a miR-29A/polyethyleneimine derivative loaded carrier: dripping the miR-29A solution into the polyethyleneimine derivative carrier obtained in the step (3), and freezing and storing; the dosage of the miR-29A is that 50ng of miR-29A is added into each milligram of polyethyleneimine derivative carrier;

(5) preparation of polyvinyl alcohol hydrogel: and (3) mixing the components obtained in the steps (1), (2) and (4) in equal volume, pouring the mixture into a mold, and refrigerating the mold at-20 ℃ overnight to obtain the polyvinyl alcohol hydrogel.

The hydrogel prepared in this example was subjected to a drug release test, fig. 7 is a drug release diagram of the hydrogel material, and it can be seen from fig. 7 that the drug is rapidly released in the first 10 hours, the release rate is about 60%, and then the rate is slowed down, and after 80 hours, the drug release rate reaches about 90% of the maximum.

The hydrogel prepared in the example is used for skin wound repair, and as can be seen from table 2, the hydrogel of the control group (example 3) has a certain difference in treatment effect with the hydrogel of the experimental group (example) within the same time, and after 14 days, the wound diameter of the control group is about half of that of the experimental group, so that it can be seen that the reduction of the rubescensin content is not beneficial to wound repair, but the example still has a certain treatment effect.

TABLE 2

Example 5

(1) preparing a polyvinyl alcohol aqueous solution: adding polyvinyl alcohol into deionized water, stirring and dissolving to obtain a polyvinyl alcohol aqueous solution, wherein the mass concentration of the polyvinyl alcohol aqueous solution is 20%, the dissolving temperature is 90 ℃, and the stirring speed is 500 r/min;

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: adding the rubescensin into the sodium alginate microsphere solution, and freeze-drying for later use; the preparation method of the sodium alginate microspheres comprises the following steps: mixing tween 80 and olive oil to obtain a mixed solution, stirring at normal temperature, dropwise adding a sodium alginate aqueous solution into the mixed solution, continuously stirring at normal temperature, adding a calcium chloride solution, stirring overnight, respectively centrifuging and washing with isopropanol and deionized water for three times, and freeze-drying to obtain sodium alginate microspheres; the concentration of the sodium alginate microsphere solution is 10mg/mL, 2mg of rubescensin is added into each milliliter of the sodium alginate microsphere solution, the freeze-drying temperature is-60 ℃, and the freeze-drying time is 24 hours;

(3) preparing a polyethyleneimine derivative carrier: preparing a hyaluronic acid solution with the mass fraction of 2% by taking deionized water as a solvent, adding 0.5g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, 1g N-hydroxysuccinimide and 5g of polyethyleneimine into each gram of hyaluronic acid, stirring at normal temperature overnight, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water for 3 times every day, and finally freeze-drying for later use, wherein the freeze-drying temperature is-60 ℃, and the freeze-drying time is 24 hours, so as to obtain a polyethyleneimine derivative carrier;

(4) preparing a miR-29A/polyethyleneimine derivative loaded carrier: dripping the miR-29A solution into the polyethyleneimine derivative carrier obtained in the step (3), and freezing and storing; the dosage of the miR-29A is that 100ng of miR-29A is added into each milligram of polyethyleneimine derivative carrier;

The hydrogel prepared in this example was subjected to a drug release test, fig. 8 is a drug release diagram of the hydrogel material, and it can be seen from fig. 8 that the drug is rapidly released in the first 10 hours, the release rate is about 50%, and then the rate is slowed down, and after 100 hours, the drug release rate reaches about 90% of the maximum value.

The hydrogel prepared in the embodiment is used for repairing skin wounds, and as can be seen from table 3, the hydrogel of the control group (embodiment 3) has the same treatment effect with the hydrogel of the experimental group (embodiment) in the same time, and it can be seen that the miR-29A content is increased to a certain extent, the wound repair effect is not obviously improved, and the experimental group and the control group both have better treatment effects.

TABLE 3

Time	Control group	Experimental group
			Day 1	10mm	10mm
Day
	3	7mm	7mm
Day 7				4mm	4mm
	Day 14	1.5mm	1.5mm

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A preparation method of polyvinyl alcohol hydrogel is characterized by comprising the following steps:

(2) preparing a rubescensin/sodium alginate loaded microsphere compound: adding the rubescensin into a sodium alginate microsphere solution, wherein the concentration of the sodium alginate microsphere solution is 5-10 mg/mL, and adding the rubescensin into the sodium alginate microsphere solution by 0.5-2 mg per milliliter; freeze-drying for later use;

(4) preparing a miR-29A/polyethyleneimine derivative loaded carrier: dripping the miR-29A solution into the polyethyleneimine derivative carrier obtained in the step (3), wherein 50-100 ng of miR-29A is added into each milligram of polyethyleneimine derivative carrier; freezing and storing;

2. The method for preparing a polyvinyl alcohol hydrogel according to claim 1, wherein in the step (1), the mass concentration of the polyvinyl alcohol aqueous solution is 5 to 20%, the dissolution temperature is 80 to 90 ℃, and the stirring speed is 300 to 500 r/min.

3. The method for preparing polyvinyl alcohol hydrogel according to claim 1, wherein in the step (2), the method for preparing sodium alginate microspheres comprises the following steps: mixing an emulsifier and vegetable oil to obtain a mixed solution, stirring at normal temperature, dropwise adding a sodium alginate aqueous solution into the mixed solution, continuously stirring at normal temperature, adding a calcium chloride solution, stirring overnight, respectively centrifugally washing with isopropanol and deionized water for three times, and freeze-drying to obtain the sodium alginate microspheres.

4. The method for preparing a polyvinyl alcohol hydrogel according to claim 1, wherein the freeze-drying temperature in the step (2) is-60 ℃ and the freeze-drying time is 24 hours.

5. The method for preparing a polyvinyl alcohol hydrogel according to claim 1, wherein in the step (3), the method for preparing the polyethyleneimine derivative carrier comprises: taking deionized water as a solvent, preparing a hyaluronic acid solution with the mass fraction of 0.5-2%, adding 0.1-0.5 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide, 0.2-1 g N-hydroxysuccinimide and 1-5 g of polyethyleneimine into each gram of hyaluronic acid, stirring overnight at normal temperature, dialyzing for three days by using a dialysis bag with the molecular weight cutoff of 10K, changing water for 2-3 times every day, and finally freeze-drying for later use, wherein the freeze-drying temperature is-60 ℃, and the freeze-drying time is 24 hours, so as to obtain the polyethyleneimine derivative carrier.

6. The method of preparing a polyvinyl alcohol hydrogel according to claim 1, wherein in the step (5), the method of preparing a polyvinyl alcohol hydrogel comprises: mixing the components obtained in the steps (1), (2) and (4) in equal volume, pouring into a mold, and refrigerating at-20 ℃ overnight.

7. A polyvinyl alcohol hydrogel produced by the production method according to any one of claims 1 to 6.

8. Use of a polyvinyl alcohol hydrogel according to claim 7 in the manufacture of a dressing for the treatment of a skin wound.