CN116036352A - Antibacterial hydrogel adhesive for promoting wound healing and preparation method and application thereof - Google Patents
Antibacterial hydrogel adhesive for promoting wound healing and preparation method and application thereof Download PDFInfo
- Publication number
- CN116036352A CN116036352A CN202310026256.9A CN202310026256A CN116036352A CN 116036352 A CN116036352 A CN 116036352A CN 202310026256 A CN202310026256 A CN 202310026256A CN 116036352 A CN116036352 A CN 116036352A
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- CN
- China
- Prior art keywords
- beta
- hydrogel
- cyclodextrin
- hydrogel adhesive
- glucan
- Prior art date
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- Granted
Links
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Abstract
The invention relates to an antibacterial hydrogel adhesive for promoting wound healing, a preparation method and application thereof. Firstly, after acidolysis activation of beta-glucan, the beta-glucan reacts with hyaluronic acid, and after dialysis and drying, beta-glucan grafted hyaluronic acid is obtained, then polyvinyl alcohol and beta-cyclodextrin are subjected to intermolecular force to generate hydrogen bond crosslinking to form a substrate of a hydrogel adhesive, so that the mechanical property and the adhesiveness of the adhesive are ensured, and the beta-glucan grafted hyaluronic acid is added to form interpenetrating network hydrogel, so that the anti-inflammatory repair function is improved, the wound healing is effectively promoted, and the scar formation is reduced. And finally, using beta-cyclodextrin as a protective agent, reducing silver nitrate by sodium borohydride to form a colloidal aqueous solution of silver nano particles, dialyzing to obtain nano silver wrapped by the beta-cyclodextrin, and adding the nano silver wrapped by the beta-cyclodextrin into the interpenetrating network hydrogel to further improve the antibacterial property of the hydrogel.
Description
Technical Field
The invention relates to the technical field of medical biological materials, in particular to an antibacterial hydrogel adhesive for promoting wound healing, and a preparation method and application thereof.
Background
The skin, which is the largest organ of the human body, provides an important natural barrier against the external environment from biological infestations of the body. Once the skin is damaged, the skin can bleed, and pathogens can easily enter the body to cause wound infection, so that inflammation and even ulceration are caused. In order to solve the problems of nursing and treating skin wounds, surgical sutures, staplers and the like are often used clinically to seal the wounds. Although the method is firmly stitched, the operation is complex, scars are easy to leave, secondary injury is caused to the wound during stitching, and certain pain and discomfort are brought during stitch removal. There is a need to develop a medical adhesive to adhere wounds together instead of conventional suturing. The existing adhesives have a plurality of defects, such as poor biocompatibility and easy wound inflammation reaction although the adhesive strength of the alpha-cyanoacrylate derivative adhesives is high. The fibrin glue developed later has good biocompatibility and degradability, but the use of the fibrin glue is limited due to the high price, long preparation time and the risk of potentially infecting viruses.
Disclosure of Invention
The invention provides an antibacterial hydrogel adhesive for promoting wound healing and a preparation method thereof, which are characterized in that polyvinyl alcohol and beta-cyclodextrin with good biocompatibility are crosslinked to synthesize a hydrogel adhesive substrate, beta-glucan grafted with hyaluronic acid is added to achieve the effects of enhancing wound repair rate and improving skin repair degree, and finally silver nano particles are added to improve the antibacterial performance of the hydrogel adhesive.
The scheme for solving the technical problems is as follows: the antibacterial hydrogel adhesive for promoting wound healing comprises a hydrogel interpenetrating network, wherein the hydrogel interpenetrating network is loaded with beta-cyclodextrin coated nano silver, and the loading amount of the beta-cyclodextrin coated nano silver is 0.02-2wt%; the hydrogel interpenetrating network consists of a hydrogel adhesive substrate synthesized by crosslinking polyvinyl alcohol and beta-cyclodextrin and a degradation activated beta-glucan grafted hyaluronic acid; the content of the hydrogel adhesive substrate is 98-99.9wt% based on the hydrogel interpenetrating network; the content of the degradation activated beta-glucan grafted hyaluronic acid is 0.1-2wt%.
The mechanical property and the adhesiveness of the adhesive are guaranteed by crosslinking the polyvinyl alcohol and the beta-cyclodextrin to synthesize the hydrogel adhesive substrate, the degradation and activation of the beta-glucan grafted hyaluronic acid are improved to resist inflammation and repair, and the beta-cyclodextrin wraps the nano silver to provide a protective layer for the nano silver particles to prevent oxidation.
Preferably, the loading of the beta-cyclodextrin coated nano silver is 2wt%, and the content of the hydrogel adhesive substrate is 99.8wt%; the content of the degradation-activated beta-glucan grafted hyaluronic acid was 0.2wt%.
Preferably, the mass ratio of the polyvinyl alcohol to the beta-cyclodextrin is 0.5-5:1.
Preferably, the particle size of the beta-cyclodextrin coated nano silver solution is 35-45nm.
The preparation method of the antibacterial hydrogel adhesive for promoting wound healing comprises the following steps:
s1, degrading and reactivating beta-glucan to obtain degraded and activated beta-glucan, wherein the degraded beta-glucan has higher purity and lower molecular weight, and the grafting rate with hyaluronic acid is improved; the degradation activation step is specifically as follows: mixing 20-80 mL of formic acid and 1-5 g of beta-glucan uniformly, heating to 75-100 ℃ for reaction for 1-4h, vacuum drying formic acid at 40-100 ℃ to a small amount, adding 20-50mL of absolute ethyl alcohol for uniform mixing, displacing glucan, centrifuging for 10-30min at the rotating speed of 4000-8000 rpm, collecting precipitate, freeze-drying for 48-72 h to obtain degraded beta-glucan, dissolving beta-glucan in 20-40 mL of ultrapure water, heating to 75-100 ℃ for reaction for 1-3h, adding 1-4 mL of epichlorohydrin for ultrasonic treatment at 20-60 ℃ for 2-6h, vacuum drying liquid at 40-100 ℃ to a small amount, adding 20-50mL of absolute ethyl alcohol for uniform mixing, displacing glucan, centrifuging for 10-30min at the rotating speed of 4000-800 rpm, collecting precipitate, and freeze-drying for 48-72 h;
s2, adding the degraded and activated beta-glucan and hyaluronic acid into 20-100mL of ultrapure water according to the mass ratio of 1:1-10, reacting for 48-60 hours at 20-80 ℃, dialyzing for 3-7 days, and freeze-drying the solution for 48-72 hours to obtain beta-glucan grafted hyaluronic acid; beta-glucan has the biological activities of diminishing inflammation, resisting tumor, resisting radiation, enhancing the immune function of an organism and the like, improves the transfer of macrophages to a wound site and promotes the deposition of collagen; hyaluronic acid has good biocompatibility, degradability and extremely high water retention, and can regulate and control cell adhesion, promote wound healing and vascularization.
S3, dispersing polyvinyl alcohol and beta-cyclodextrin in 10-80 mL of ultrapure water, adding boric acid, heating to 75-100 ℃ and stirring for reaction for 1-4 hours to obtain a hydrogel adhesive substrate; adding beta-glucan grafted hyaluronic acid into a hydrogel adhesive substrate, and stirring and reacting for 0.5-3 hours at the temperature of 30-60 ℃ to obtain a hydrogel interpenetrating network; wherein boric acid is added in an amount of 1 to 3wt% of the substrate of the hydrogel adhesive,
s4, mixing and stirring the beta-cyclodextrin solution with the concentration of 10-100 mM and the silver nitrate solution with the concentration of 1-6 mM for 1-6 hours, adding the sodium borohydride solution with the concentration of 10-100 mM at the speed of 2-8S per drop, reacting under the ice bath condition, dialyzing for 3-10 days to obtain beta-cyclodextrin coated nano silver (beta-CD/AgNPs solution), adding the beta-cyclodextrin coated nano silver solution into a hydrogel interpenetrating network, and stirring for reacting to obtain a hydrogel adhesive; wherein the volume ratio of the beta-cyclodextrin solution, the silver nitrate solution and the sodium borohydride solution is 1:0.5-2:0.5-2.
Preferably, in the step S2, the mass ratio of the degradation activated beta-glucan to the hyaluronic acid is 1:5; the purity of the hyaluronic acid is 90% -99%.
Preferably, in the step S3, the alcoholysis degree of the polyvinyl alcohol is 88% -99%, and the addition amount of the boric acid is 2% by weight of the substrate of the hydrogel adhesive.
Preferably, in S4, the volume ratio of the beta-cyclodextrin solution, the silver nitrate solution and the sodium borohydride solution is 1:1:1.
Preferably, in S4, the concentration of the beta-cyclodextrin solution is 50mM; the silver nitrate solution had a concentration of 6mM and the sodium borohydride solution had a concentration of 50mM.
The invention also provides an application of the antibacterial hydrogel adhesive for promoting wound healing in medical repair of wound materials.
The beneficial effects of the invention are as follows:
1. the raw materials selected by the invention have good biocompatibility, the beta-glucan and the hyaluronic acid are natural macromolecular polysaccharide, the sources are wide, and the price is low; polyvinyl alcohol, beta-cyclodextrin are certified as safe ingredients.
2. The invention combines the advantages of two materials by the beta-glucan grafted hyaluronic acid, and overcomes the defects of insoluble beta-glucan, difficult degradation and poor mechanical strength of the hyaluronic acid. The hydrogel adhesive has the advantages of increasing the wound healing efficiency, promoting the aggregation and adhesion of fibroblasts, reducing scar formation and the like, and has better healing effect than common surgical suture lines.
3. According to the invention, the silver nano particles are introduced, so that the antibacterial performance of the hydrogel adhesive is improved, the sterilization rate of escherichia coli and staphylococcus aureus reaches 99.9%, and inflammation caused by bacterial infection can be effectively prevented; can enhance the electric signal conduction among cells and accelerate the wound healing when being matched with the electric stimulation treatment.
The foregoing description is only an overview of the present invention, and is intended to provide a better understanding of the present invention, as it is embodied in the following description, with reference to the preferred embodiments of the present invention and the accompanying drawings. Specific embodiments of the present invention are given in detail by the following examples and the accompanying drawings.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiments of the invention and together with the description serve to explain the invention and do not constitute a limitation on the invention. In the drawings:
FIG. 1 is a schematic diagram showing the experimental results of lap shear force in example 1 and comparative examples 1-2 of the present invention;
FIG. 2 is a photograph showing colonies of example 1 and comparative example 1 of the present invention in an antibacterial test (the test bacterium is Escherichia coli);
FIG. 3 is a photograph showing colonies of example 1 and comparative example 1 of the present invention in an antibacterial test (the test bacterium is Staphylococcus aureus);
FIG. 4 is a schematic diagram showing the cytotoxicity test results of example 1 and comparative example 1 according to the present invention;
FIG. 5 is a photograph showing the experimental results of the skin wound model of the electrically stimulated rats in example 1 and comparative example 1 of the present invention.
Detailed Description
The principles and features of the present invention are described below with reference to the drawings, the examples are illustrated for the purpose of illustrating the invention and are not to be construed as limiting the scope of the invention.
The working principle of the invention is as follows: according to the invention, firstly, polyvinyl alcohol and beta-cyclodextrin are crosslinked through intermolecular force to generate hydrogen bonds to synthesize a substrate of the hydrogel adhesive, the mechanical property and adhesiveness of the adhesive are guaranteed, beta-glucan and hyaluronic acid are added to form interpenetrating network hydrogel, the anti-inflammatory repair function is improved, and finally, silver nano particles wrapped by the beta-cyclodextrin are added to improve the antibacterial property of the hydrogel and enhance the electrical signal conduction between cells by matching with electrical stimulation treatment, so that angiogenesis and cell proliferation are promoted, and the wound healing process is accelerated. The hydrogel adhesive can be used as a medium to conduct external electric signals to all parts of the wound while filling the wound, so that the wound repair process is quickened.
Example 1
S1, weighing 2g of beta-glucan, dissolving in 40mL of formic acid solution, reacting for 4 hours in an oil bath at 90 ℃, vacuum drying formic acid at 90 ℃ to a small amount, adding 50mL of absolute ethyl alcohol to replace the glucan, centrifuging for 10 minutes at a rotating speed of 8000rpm, collecting precipitate, and freeze-drying for 48 hours. Adding the dried precipitate into 40mL of ultrapure water, reacting for 2 hours at 90 ℃, adding 4mL of epichlorohydrin for activation, performing ultrasonic treatment at 60 ℃ for 6 hours, then vacuum drying at least a liquid in the solution at 90 ℃, adding 50mL of absolute ethyl alcohol, centrifuging for 20 minutes at 8000rpm, taking the precipitate, and freeze-drying for 48 hours to obtain the degraded and activated beta-glucan.
S2, adding 0.8g of glucan and 4g of hyaluronic acid into 100mL of ultrapure water, reacting for 60 hours in a water bath at 40 ℃, dialyzing for 7 days, and freeze-drying the solution for 72 hours to obtain the beta-glucan grafted hyaluronic acid.
S3, weighing 3g of polyvinyl alcohol and 2g of beta-cyclodextrin, dispersing in 80mL of ultrapure water, adding boric acid as a cross-linking agent, heating and stirring for 3 hours in a water bath kettle with the temperature above 90 ℃ to obtain a hydrogel adhesive substrate, adding 200mg of beta-glucan grafted hyaluronic acid into the substrate, and stirring for 2 hours in a water bath with the temperature of 60 ℃ to obtain the hydrogel interpenetrating network; taking a hydrogel interpenetrating network as a reference; boric acid was added in an amount of 2wt%.
S4, using beta-cyclodextrin as a protective agent and sodium borohydride as a reducing agent, and synthesizing beta-cyclodextrin coated silver nano particles by a chemical reduction method; adding 100mL of 50mM beta-cyclodextrin solution into 100mL of 6mM silver nitrate solution, magnetically stirring for 6h, adding 200mL of 50mM sodium borohydride solution, reducing in ice-water bath, and dialyzing for 7 days to obtain beta-cyclodextrin coated nano silver solution; and adding the prepared beta-cyclodextrin coated nano silver solution into the hydrogel interpenetrating network according to the proportion of 2 weight percent, and fully stirring for 60 minutes to obtain the nano silver loaded hydrogel adhesive.
Comparative example 1
Comparative example 1 the same procedure as in example 1 was followed, except that the treatment of step S4 was not performed, to obtain a hydrogel adhesive without nano silver loading.
Comparative example 2
Comparative example 2 the same procedure as in comparative example 1 was conducted except that the amount of polyvinyl alcohol added in step S3 was 1g, to obtain a nanosilver-supported hydrogel adhesive.
Characterization test of examples and comparative examples
1. Lap shear test: 0.1g of the hydrogel adhesives prepared in comparative examples 1, 2 and example 1 were uniformly coated on two glass slides with a coating area of 20 mm. Times.20 mm, respectively, and the two glass slides were lapped together and left at room temperature for 12 hours. Then, a tensile test was performed at room temperature using a universal mechanical tester at a tensile speed of 10mm/min. Shear strength = maximum force/bond area when the slide is pulled apart.
As a result, as shown in fig. 1, comparative example 2 showed the lowest adhesive strength, and comparative example 1 and example 1 showed close adhesive strength, indicating that a lower proportion of polyvinyl alcohol in the synthesis of the hydrogel adhesive substrate resulted in a decrease in the tackiness of the hydrogel adhesive.
2. Antibacterial test:
the antibacterial performance of the material is characterized by calculating the number of bacterial colonies after diluting and coating bacterial liquid.
Sterilization rate% = (control CFU number-experimental CFU number)/(control CFU number) ×100%
Bacteria for detection: coli (Escherichia coli ATCC 25922), staphylococcus aureus (Staphylococcus aureus ATCC 6538).
0.3g of the hydrogel adhesives prepared in example 1 and comparative example 1, respectively, were sterilized and then added to a composition containing 2X 10 6 ~2×10 8 Mixing CFU/mL of escherichia coli and staphylococcus aureus bacterial liquid in a test tube at 37 ℃ for 1-5 hours, diluting 500 times by using phosphate buffer solution (PBS, pH=7.4), taking 100 mu L of the diluted liquid, coating the diluted liquid on an agar plate, placing the agar plate in a 37 ℃ incubator for culturing for 12-24 hours, observing the result and counting the colony number. A blank group is additionally arranged and contains 2×10 6 ~2×10 8 Mixing CFU/mL of escherichia coli and staphylococcus aureus bacterial liquid in a test tube at 37 ℃ for 1-5 hours in a shaking table, diluting 500 times by using phosphate buffer (PBS, pH=7.4), taking 100 mu L of the diluted liquid, coating the diluted liquid on an agar plate, placing the agar plate in a 37 ℃ incubator for culturing for 12-24 hours, observing the result and counting the colony number.
As a result, as shown in FIGS. 2 to 3, the colony count of comparative example 1 was not significantly changed from that of the blank group, and the colony count of example 1 was significantly reduced. The hydrogel adhesive loaded with nano silver has antibacterial effect. The antibacterial rate is shown in Table 1.
Table 1 antibacterial ratio of hydrogel adhesives obtained in example 1 and comparative example 1
| Project | Comparative example 1 | Example 1 |
| Coli antibacterial rate/% | 10.35 | 99.99 |
| Staphylococcus aureus antibacterial rate/% | 5.09 | 99.99 |
3. In vitro cytotoxicity test: the hydrogel adhesives prepared in example 1 and comparative example 1 were sterilized and then soaked in a medium at a concentration of 0.1g/mL for 24 hours, and then fibroblasts were seeded in 96-well plates at a seeding density of 5000 cells/well. The well plate was placed in an incubator at 37℃for 24 hours, the medium was sucked away, and the medium soaked with the hydrogel adhesive was transferred to a 96-well plate, and the culture was continued in the incubator. After 24h, the medium was discarded, after washing twice with PBS buffer, a mixture of MTT (thiazole blue) and medium was added in a dark place to each well, the mixture ratio of MTT and medium was 1:9, after incubation for 4h at 37℃the supernatant was carefully aspirated, 200. Mu.L of dimethyl sulfoxide (DMSO) was added to each well to dissolve the blue-violet crystals at the bottom of the well plate, and absorbance was measured at 490nm using an enzyme-labeled instrument. Wherein the culture medium is a negative control group, and the culture medium mixed solution containing 10% of phenol is a positive control group.
As a result, as shown in FIG. 4, it can be seen that the cell viability of comparative example 1 and example 1 was 92.98% and 95.32%, respectively, and the toxicity grade of the material was grade 1.
4. Blood compatibility test: the hydrogel adhesives prepared in example 1 and comparative example 1 were respectively immersed in physiological saline at a dilution ratio of 4:5 by diluting the anticoagulated blood with physiological saline, water-bathing at 37℃for half an hour, then adding diluted blood sample (0.2 mL diluted blood sample/10 mL physiological saline), then incubating in a water-bath at 37℃for 1 hour, centrifuging for 5 minutes, and measuring absorbance of the supernatant at 545nm with an ultraviolet spectrophotometer. Wherein ultrapure water is used as a positive control group, and physiological saline is used as a negative control group. The results are shown in Table 2, and the hydrogel adhesives prepared in example 1 and comparative example 1 each achieved a safety rating.
TABLE 2 haemolysis test results of hydrogel adhesives of example 1 and comparative example 1
| Project | Comparative example 1 | Example 1 |
| Rate of hemolysis/% | 1.8 | 2.3 |
| Results (hemolysis rate < 5%, safety) | Secure | Secure |
5. Anti-inflammatory repair function test: the beta-glucan grafted hyaluronic acid obtained in the step S2 of example 1 was taken, sterilized, and then soaked in a medium at concentrations of 0.02%, 0.2% and 2% for 24 hours, respectively, and then fibroblasts were seeded in 96-well plates at a seeding density of 5000 pieces/well. Culturing the well plate in a 37 ℃ incubator for 24 hours, sucking away the culture medium, transferring the culture medium soaked with the materials into a 96 well plate, and continuing culturing in the incubator. After 48h, the medium was discarded, after washing twice with PBS buffer, a mixture containing MTT and medium was added in a ratio of 1:9 in the dark to each well, after incubation at 37℃for 4h, the supernatant was carefully aspirated, 200. Mu.L of dimethyl sulfoxide (DMSO) was added to each well to dissolve the blue-violet crystals at the bottom of the well plate, absorbance was measured at 490nm with a microplate reader, and the cell proliferation rate was calculated, and the results are shown in Table 3.
TABLE 3 results of cell experiments with different concentrations of beta-glucan grafted hyaluronic acid
| Concentration of | 0.02% | 0.2% | 2% |
| Cell proliferation rate/% (n=3) | 110.2 | 125.2 | 95.5 |
6. Electrical stimulation cell experiment: the preparation of example 1 and comparative example 1 was fixed on the bottom of a 24-well plate, immersed in 75% ethanol, dried in the air, washed well with PBS buffer, immersed in the medium for 24 hours, and then the medium was discarded. Fibroblasts were seeded on a hydrogel in a 24-well plate at a density of 2000 cells/well, and after cells had grown on the hydrogel in an adherent manner, were electrically stimulated, using the culture medium as a control group. After 48h, the medium was discarded, after washing each well twice with PBS, 200. Mu.L of a mixture of CCK-8 and the medium was added in the dark, the mixing ratio of CCK-8 and the medium was 1:9, after incubation for 1h at 37℃100. Mu.L was taken in a 96-well plate, absorbance was measured at 450nm with a microplate reader, and the cell proliferation rate was calculated. The results are shown in table 3, which demonstrates that the hydrogel adhesive loaded with silver nanoparticles can enhance the intercellular electrical signal transmission and accelerate the wound healing process under electrical stimulation.
TABLE 4 results of electro-stimulated cell experiments with the hydrogel adhesives of example 1 and comparative example 1
| Project | Comparative example 1 | Example 1 |
| Cell proliferation rate/% (n=3) | 113.7 | 139.5 |
7. Experimental procedure of electrically stimulated rat skin wound model: after the rats were anesthetized, the backs were dehaired and sterilized with 75% ethanol, after which three 1.5cm wounds were created on the backs, the first wound being untreated as a blank, and the second and third wounds being respectively smeared and adhered with the hydrogel adhesives prepared in comparative example 1 and example 1, and wound healing was performed for half an hour under 100mV voltage. As shown in fig. 5, the hydrogel adhesive treated with the hydrogel adhesive of example 1 showed the best wound healing effect, and the silver nanoparticle-loaded hydrogel adhesive enhanced the intercellular electrical signal transmission and accelerated the wound healing process.
The above description is only of the preferred embodiments of the present invention, and is not intended to limit the present invention in any way; those skilled in the art will readily appreciate that the present invention may be implemented as shown in the drawings and described above; however, those skilled in the art will appreciate that many modifications, adaptations, and variations of the present invention are possible in light of the above teachings without departing from the scope of the invention; meanwhile, any equivalent changes, modifications and evolution of the above embodiments according to the essential technology of the present invention still fall within the scope of the present invention.
Claims (10)
1. The antibacterial hydrogel adhesive for promoting wound healing is characterized by comprising a hydrogel interpenetrating network, wherein the hydrogel interpenetrating network is loaded with beta-cyclodextrin coated nano silver, and the loading amount of the beta-cyclodextrin coated nano silver is 0.02-2wt%; the hydrogel interpenetrating network consists of a hydrogel adhesive substrate synthesized by crosslinking polyvinyl alcohol and beta-cyclodextrin and a degradation activated beta-glucan grafted hyaluronic acid; the content of the hydrogel adhesive substrate is 98-99.9wt% based on the hydrogel interpenetrating network; the content of the degradation activated beta-glucan grafted hyaluronic acid is 0.1-2wt%.
2. The antimicrobial hydrogel adhesive for promoting wound healing according to claim 1, wherein the beta-cyclodextrin encapsulates the nano silver in an amount of 2wt%, and the hydrogel adhesive substrate is in an amount of 99.8wt%; the content of the degradation-activated beta-glucan grafted hyaluronic acid was 0.2wt%.
3. The antimicrobial hydrogel adhesive for promoting wound healing according to claim 1, wherein the mass ratio of polyvinyl alcohol to beta-cyclodextrin is 0.5-5:1.
4. The antibacterial hydrogel adhesive for promoting wound healing according to claim 1, wherein the particle size of the beta-cyclodextrin coated nano-silver solution is 35-45nm.
5. A method of preparing an antimicrobial hydrogel adhesive for promoting wound healing according to any one of claims 1 to 4, comprising the steps of:
s1, degrading and reactivating beta-glucan to obtain degradation-activated beta-glucan;
s2, adding the degraded and activated beta-glucan and hyaluronic acid into ultrapure water according to the mass ratio of 1:1-10, reacting at 20-80 ℃ for 48-60 hours, and obtaining beta-glucan grafted hyaluronic acid through dialysis and freeze drying;
s3, dispersing polyvinyl alcohol and beta-cyclodextrin in ultrapure water, adding boric acid, heating to 75-100 ℃ and stirring for reaction for 1-4 hours to obtain a hydrogel adhesive substrate; adding beta-glucan grafted hyaluronic acid into a hydrogel adhesive substrate, and stirring and reacting for 0.5-3 hours at the temperature of 30-60 ℃ to obtain a hydrogel interpenetrating network; wherein boric acid is added in an amount of 1-3wt% of the substrate of the hydrogel adhesive;
s4, mixing and stirring the beta-cyclodextrin solution with the concentration of 10-100 mM and the silver nitrate solution with the concentration of 1-6 mM for 1-6 hours, adding the sodium borohydride solution with the concentration of 10-100 mM for reaction under the ice bath condition, dialyzing to obtain the beta-cyclodextrin coated nano silver solution, adding the beta-cyclodextrin coated nano silver solution into the hydrogel interpenetrating network, and stirring for reaction to obtain the hydrogel adhesive; wherein the volume ratio of the beta-cyclodextrin solution, the silver nitrate solution and the sodium borohydride solution is 1:0.5-2:0.5-2.
6. The method for preparing the antibacterial hydrogel adhesive for promoting wound healing according to claim 5, wherein in the step S2, the mass ratio of the degradation activated beta-glucan to the hyaluronic acid is 1:5; the purity of the hyaluronic acid is 90% -99%.
7. The method for preparing an antibacterial hydrogel adhesive for promoting wound healing according to claim 5, wherein in the step S3, the alcoholysis degree of polyvinyl alcohol is 88% -99%, and the addition amount of boric acid is 2% by weight of the substrate of the hydrogel adhesive.
8. The method for preparing an antibacterial hydrogel adhesive for promoting wound healing according to claim 5, wherein the volume ratio of the beta-cyclodextrin solution, the silver nitrate solution and the sodium borohydride solution in the S4 is 1:1:1.
9. The method of preparing an antibacterial hydrogel adhesive for promoting wound healing according to claim 5, wherein in S4, the concentration of the beta-cyclodextrin solution is 50mM; the silver nitrate solution had a concentration of 6mM and the sodium borohydride solution had a concentration of 50mM.
10. Use of an antibacterial hydrogel adhesive for promoting wound healing according to any one of claims 1 to 4 in medical repair of wound materials.
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