CN115634308A - Polyethylene glycol biological adhesive and preparation method and application thereof - Google Patents
Polyethylene glycol biological adhesive and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a polyethylene glycol biological adhesive and a preparation method and application thereof, belonging to the technical field of new medical materials. The method comprises the following steps: (1) Mixing Tetra-PEG-NH 2 Dissolving in ultrapure water to prepare a first solution with the concentration of 5-25 wt%, and placing on ice; (2) Dissolving Tetra-PEG-SC in ultrapure water to prepare a second solution with the concentration of 5-25 wt%, and placing on ice; (3) Dissolving oxidized starch in ultrapure water to prepare a third solution with the concentration of 0.5-1.5 weight percent, and placing the third solution on ice; (4) Mixing the first solution, the second solution and the third solution to obtain a biological adhesive; wherein the first solution: a second solution: the volume ratio of the third solution is 5-20:5-20:1. the biological adhesive prepared by the invention has the advantages of quick gelling, no toxicity, strong adhesiveness, strong tensile strength and the like.
Description
Technical Field
The invention relates to the technical field of new medical materials, in particular to a polyethylene glycol biological adhesive and a preparation method and application thereof.
Background
Meniscus injury is the most common injury of knee joint movement in life and has received increasing attention. The traditional treatment method generally adopts arthroscopic meniscus suture/excision, wherein the damaged meniscus is sutured as much as possible, and the suture is extremely difficult to trim and excise. Complications that may occur in patients after clinical meniscal removal/suturing trauma surgery include joint effusion/hematocele, interstitial edema, cartilage damage, stiffness of the knee joint, deep vein thrombosis, common peroneal nerve injury, synovial hernia. Generally, the operation time of the clinical resection/revision meniscal surgery is about half an hour, and the operation time of suturing the meniscus injury is about one hour, which is a relatively long operation time for a patient. And the chondroprotective effect after surgical resection is lost, and the patient develops knee osteoarthritis in the terminal stage.
Bioadhesives have been developed to replace intraoperative sutures in the hope of addressing the complex types of meniscal injuries. Bioadhesives are generally divided into natural and synthetic bioadhesives. Natural bioadhesives, represented by fibrin glue, have greatly limited their use due to weak adhesive strength and cross-contamination of blood products. The synthetic biological adhesives are represented by cyanoacrylate derivatives, have high strength, but have poor biocompatibility, toxic degradation products and greatly limited clinical application, and the biological adhesives do not have the biological function of promoting meniscus repair. At present, researchers develop a plurality of novel biological adhesives, although the novel biological adhesives have certain strength and good biocompatibility, the biological adhesives are usually multi-component, high-strength ultraviolet light irradiation or high-temperature coagulation promotion is needed during application and synthesis, the operation is complex, the required time is long, the activity of normal cells is damaged, and the like, so that the operation time, the cost and the difficulty are greatly improved.
Disclosure of Invention
In order to solve one or more technical problems in the prior art, the invention provides a polyethylene glycol biological adhesive and a preparation method and application thereof.
The first object of the present invention is to provide a method for preparing a polyethylene glycol bioadhesive, wherein the method comprises the following steps: (1) Tetra-PEG-NH 2 Dissolving in ultrapure water to prepare a first solution with the concentration of 5-25 wt%, and placing on ice; (2) Dissolving Tetra-PEG-SC in ultrapure water to prepare a second solution with the concentration of 5-25 wt%, and placing on ice; (3) Dissolving oxidized starch in ultrapure water to prepare a third solution with the concentration of 0.01-0.2 weight percent, and placing the third solution on ice; (4) Mixing the first solution, the second solution and the third solution to obtain a biological adhesive; wherein the first solution: a second solution: the volume ratio of the third solution is 5-20:5-20:1.
the second object of the present invention is to provide a polyethylene glycol bioadhesive prepared by the above preparation method.
The third purpose of the invention is to provide the application of the polyethylene glycol biological adhesive prepared by the preparation method in preparing products for treating meniscus injury.
The biological adhesive prepared by the invention has the following advantages: 1. the gelling is rapid, the gelling time is only 1s-5min, and the time can be regulated and controlled; 2. water is non-toxic; 3. the adhesive has strong adhesiveness and toughness, and can resist tensile rise, after the meniscus is intersected, the meniscus is adhered by using the biological adhesive, a self-made stretching instrument is used for clamping the rear corner of the meniscus, a weight of 200g is used for clamping the front corner of the meniscus, the meniscus is suspended for more than 1 hour, and the meniscus intersection is tightly adhered; 4. the gel is directly formed, steps such as blue light/ultraviolet light and the like are not needed, cells/cytokines and the like are not damaged, the gel can be used as a carrier, various components are packaged, and the application range is wide; 5. metabolism and controllable degradation time; 6. promoting meniscus repair.
Drawings
FIG. 1 is a reaction scheme for preparing the polyethylene glycol bioadhesive of the present invention.
FIG. 2 is a cross-linking process of the polyethylene glycol bioadhesive prepared in example 1 of the present invention.
FIG. 3 is an electron microscope image of the solid content of the final product after gelling the polyethylene glycol bioadhesive prepared in examples 1-4 of the present invention.
FIG. 4 is a view showing the observation of chronic dehydration under constant temperature and humidity conditions of the final product after gelling of the polyethylene glycol bioadhesive prepared in examples 1 to 4 of the present invention.
FIG. 5 is a view showing the elastic pressure observation of the polyethylene glycol bioadhesive prepared in example 1 of the present invention.
FIG. 6 is a graph of tensile strength of comparative different glues for in vitro bonded menisci of the polyethylene glycol bioadhesive of example 1 of the present invention.
FIG. 7 is a graph of the arthroscopic water pressure resistance of the polyethylene glycol bioadhesive prepared in example 1 of the present invention compared to different glues.
FIG. 8 is a diagram of viable cells stained for dead and live cultured chondrocytes in the polyethylene glycol bioadhesive prepared in example 1 of the present invention.
FIG. 9 is a dead cell image of dead and live staining of cultured chondrocytes in a polyethylene glycol bioadhesive prepared in example 1 of the present invention.
Detailed Description
The invention provides a preparation method of a polyethylene glycol biological adhesive, wherein the method comprises the following steps: (1) Mixing Tetra-PEG-NH 2 Dissolving in ultrapure water to prepare a first solution with the concentration of 5-25 wt%, and placing on ice; (2) Dissolving Tetra-PEG-SC in ultrapure water to prepare a second solution with the concentration of 5-25 wt%, and placing on ice; (3) Dissolving oxidized starch in ultrapure water to prepare a third solution with the concentration of 0.01-0.2 weight percent, and placing the third solution on ice; (4) Mixing the first solution, the second solution and the third solution to obtain a biological adhesive; wherein the first solution: a second solution: the volume ratio of the third solution is 5-20:5-20:1.
in the present invention, tetra-PEG-NH 2 Is provided with-NH 2 A four-arm PEG (polyethylene glycol) for modifying group, preferably Tetra-PEG-NH 2 The molecular weight of (A) is 15000-25000, and the four-arm PEG is a product which can be directly purchased in the market.
The Tetra-PEG-SC is a four-arm PEG with a-SC modification group, preferably the molecular weight of the Tetra-PEG-SC is 15000-25000, and the four-arm PEG is a product which can be directly purchased in the market.
The source of the oxidized starch and the like in the present invention is not particularly limited, and the molecular weight of the oxidized starch is preferably 650 to 750, which is a commercially available product directly.
According to some preferred embodiments, in step (4), the first solution: a second solution: the volume ratio of the third solution may be 5-15:5-15:1.
according to some preferred embodiments. The concentration of the first solution is 5 to 20% by weight, and more preferably 8 to 12% by weight.
According to some preferred embodiments, the concentration of the second solution is 5 to 20 wt.%, further preferably 8 to 12 wt.%.
According to some preferred embodiments, the concentration of the third solution is 0.05 to 0.15 wt%.
According to some preferred embodiments, the porosity of the bioadhesive is from 6 to 16 μm; the change of compression resilience at 25-85 ℃ is less than or equal to 1 percent.
In a second aspect, the present invention provides a polyethylene glycol bioadhesive prepared by the preparation method according to the first aspect of the present invention.
In a third aspect, the invention provides the use of a polyethylene glycol bioadhesive prepared by the preparation method of the first aspect of the invention in the preparation of a product for treating meniscal damage.
In some preferred embodiments of the invention, the application comprises the steps of: s1, adding a biological adhesive into the damaged meniscus; s2, curing the biological adhesive. Preferably, the curing temperature is 10-25 ℃ and the curing time is 1s-5min.
The biological adhesive is prepared into a solution I, a solution II and a solution III in advance, the solutions are stored in a three-cavity syringe with a complete design and are hermetically stored at 4 ℃, a patient with meniscus injury is completely anesthetized and disinfected, irregular burr parts on the edges of the meniscus tear are cleaned by using a knee arthroscopic surgery, the meniscus tear is relatively smooth and is aligned correctly, the biological adhesive is injected to the meniscus tear through the three-cavity syringe specially made, the tear is aligned slightly, and the biological adhesive is completely cured after 1s-5min.
The invention will be further illustrated by way of example, but the scope of protection is not limited to these examples. The present invention is capable of other embodiments, and various modifications and changes can be made by those skilled in the art without departing from the spirit and scope of the invention.
The test methods referred to in the following examples and comparative examples are as follows:
1. scanning Electron Microscopy (SEM) A field emission scanning electron microscope, model Sigma 300, manufactured by ZEISS, germany, was used, with porosity testing being performed by SEM.
2. The compression and stretching instrument adopts an INSTRON 3365 type mechanical testing instrument manufactured by INSTRON corporation in America.
3. The analysis of the living and dead cells adopts a dead and live staining detection kit (KGAF 001) produced by Kaiky biology company of China.
Fluorescence microscope operation, fluorescence microscope operation
1.1 remove the reagent stock solution of calcein (calcein AM) and Propidium Iodide (PI) and equilibrate for 30 minutes at room temperature.
1.2 Add 5. Mu.L of 16mm PI stock solution to 10mL Chinese (PBS), vortex and mix well to get 8 μm PI solution.
1.3 Add 5. Mu.L of 4mm stock solution of calcein AM to 10mL of PI solution and vortex to ensure adequate mixing.
1.4 the resulting working solution (2 μm calcein AM and 8 μm PI) was used directly for staining cells. Note that: aqueous solutions of calcein AM are susceptible to hydrolysis and should be used up the day.
Preparation of cells and development of experiments
1.5 adherent and non-adherent cells were mounted in flasks or chamber slides.
1.6 before the experiment was started, the cells were washed to ensure removal of the active esterase contained in the medium. Adherent cells were washed gently with PBS and the supernatant removed. Non-adherent cells were collected by centrifugation tube and centrifuged, and the supernatant was removed by washing with PBS.
1.7 add sufficient working solution to ensure that a monolayer of cells is submerged.
1.8 and incubating for 30-45 minutes at room temperature.
1.9 for adherent cells, aspirate staining broth to stop incubation. Add 10. Mu.L of PBS to a clean slide, cover the slide, seal with nail polish to prevent water evaporation.
2.0 fluorescent microscope observation of labeled cells.
2. Fluorescent microplate handling
Preparation of working solution (calcein AM 2 μm, PI 8 μm)
2.1 taking out the stock solutions of the reagent of the calcein AM and the PI, and balancing for 30 minutes at room temperature.
2.2 Add 5. Mu.L of 16mm PI stock to 10mL PBS and vortex and mix well to get 8 μm PI solution.
2.3 Add 5. Mu.L of 4mm calcein AM stock to 10mL of PI solution and vortex to ensure adequate mixing.
2.4 working solution (2 μm calcein AM and 8 μm PI) obtained.
2.5 if the ratio of live and dead cells needs to be calculated separately, 1mL of 2 μm calcein AM solution and 1mL of 8 μm PI solution are prepared separately.
Preparation of cells and development of experiments
The minimum monitoring value of each hole of cells is about 200 to 500, and the maximum common cell detection value of each hole is about 106.
2.6 culturing adherent or suspension cells. Control samples of live cells versus dead cells were prepared. Dead cells were treated with 0.1% saponin or 0.1 to 0.5% digitonin for 10 minutes.
2.7 washing cells with PBS. For adherent cells, 100 μ L of PBS was added to cover the bottom of the wells, and for suspension cells, the tubes were directly manipulated and resuspended in PBS. Buffer containing cells, 100. Mu.L per well, was added to each well of the microplate. Washing of the cell sample is done with care to ensure removal of active esterase in the culture medium, which would otherwise cause background.
Measuring fluorescence using a fluorescent microplate reader
In order to obtain the best sensitivity, the used microplate reader adopts a signal exciter with an optical filter to ensure that the microplate reader does not interfere with each other. Calcein can be excited with a fluorescent optical filter (485. + -.10 nm), while PI can be compatible with a typical rhodamine optical filter (530. + -.12.5 nm). While the emitted light signals can be well separated by optical filters, the calflavin 530 + -12.5 nm and the PI 645 + -20 nm.
2.8 percent dead cells of control experimental samples were prepared if necessary. If the relative increase in dead and live cells is measured, the control may not be set. The control samples may have: cell-free control (G, H), live cell control (E, F) and dead cell control (C, D).
2.9 Add 100. Mu.L of the calcein AM and PI stock solution to each well in a final volume of 200. Mu.L, containing 1 μm calcein and 4 μm PI at final concentrations. And incubating for 30 to 45 minutes at room temperature.
2.10 sample data was collected using appropriate excitation and emission filters.
The invention is described below by means of specific examples.
Example 1
(1) Weighing Tetra-PEG-NH 2 (purchased from Xylongson, product No. 06020700212, molecular weight 2W) 0.05mg was added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) 0.05mg of Tetra-PEG-SC (purchased from Hebei Lihua biology, product number 65996-62-5, molecular weight 2W) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a second solution.
(3) 0.001mg of oxidized starch (purchased from Xiamen Sainungge, product number 06020702012, molecular weight 690.6) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a third solution.
(4) Measuring the first/second/third solution according to the ratio of 10:10:1 at room temperature for 1s to obtain the polyethylene glycol biological binder. The gluing process is shown in figure 2. The microstructure after gluing is shown in fig. 3. The cross-linking process for preparing the polyethylene glycol biological binder provided by the embodiment of the invention is very rapid, the polyethylene glycol biological binder can be bonded and finished within 1s at normal temperature, the bonding process of the polyethylene glycol biological binder is safe and simple, other conditions such as high-temperature ultraviolet are not needed, and a good biological safety reaction foundation is laid for further biological application of the polyethylene glycol biological binder.
Example 2
(1) Weighing Tetra-PEG-NH 2 (purchased from Xiamenocong, product number 06020700212, molecular weight 2W) 0.1mg was added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) 0.1mg of Tetra-PEG-SC (purchased from Hebei Lihua biology, product number 65996-62-5, molecular weight 2W) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a second solution.
(3) 0.001mg of oxidized starch (purchased from Xiamen Sainungge, product number 06020702012, molecular weight 690.6) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a third solution.
(4) The first/second/third solution was measured as 10:10:1 at room temperature for 1s to obtain the polyethylene glycol biological binder. The microstructure after crosslinking is shown in FIG. 3.
Example 3
(1) Weighing Tetra-PEG-NH 2 (purchased from Xiamen Sainumbange, product number 06020700212, molecular weight 2W) 0.15mg was added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) 0.15mg of Tetra-PEG-SC (purchased from Hebei Lihua biology, product number 65996-62-5, molecular weight 2W) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a second solution.
(3) 0.001mg of oxidized starch (purchased from Xiamen Sainungge, product number 06020702012, molecular weight 690.6) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a third solution.
(4) The first/second/third solution was measured as 10:10:1 for 1s at room temperature to obtain the polyethylene glycol biological binder. The microstructure after cross-linking is shown in figure 3.
Example 4
(1) 0.2mg of Tetra-PEG-NH2 (purchased from Xiamenocong, product number 06020700212, molecular weight 2W) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a first solution.
(2) 0.2mg of Tetra-PEG-SC (product number 65996-62-5, molecular weight 2W, available from Rieharihua biology, hebei) is weighed and added into 1mL of ultrapure water, and stirred at 4 ℃ for 5min to react, thus obtaining a second solution.
(3) 0.001mg of oxidized starch (purchased from Xiamen Sainungge, product number 06020702012, molecular weight 690.6) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a third solution.
(4) The first/second/third solution was measured as 10:10:1 at room temperature for 1s to obtain the polyethylene glycol biological binder. The microstructure after crosslinking is shown in FIG. 3.
As shown in fig. 3, the microstructure of the gelled polyethylene glycol modified compound bioadhesive of the embodiment of the present invention is filled with the cavity structures, and with the change of the pore diameters of the cavity structures with different solid contents, the existence of a large number of pore structures of the bioadhesive in the microscopic fields of examples 1 to 4 can be clearly observed by using a scanning electron microscope, so that cells can freely shuttle in the bioadhesive and cling to the bioadhesive to grow in a crawling manner during biological application.
As shown in fig. 4, the microstructures of the bioadhesive prepared by the inventive examples were filled with the hollow structures and contained a large amount of moisture, and the bioadhesive was gradually dehydrated until stable in a constant temperature and humidity environment with the lapse of time, and it was observed that the dehydration efficiency of the bioadhesive of examples 1 to 4 was different in terms of solid content.
As shown in fig. 5, the bio-adhesive prepared from the polyethylene glycol modified compound according to the embodiment of the present invention has excellent compression resilience, and after repeated compression using a compression-extensometer and observing a plurality of cycles of examples 1 to 4, no significant deformation occurs, and the bio-adhesive can still completely rebound, and can effectively resist a pressure environment during bio-application.
The biological adhesive for preparing the polyethylene glycol modified compound in the embodiment of the invention has high biological safety, cartilage cells are cultured in the biological adhesive in the embodiment 1, and after 2 weeks, the observation shows that the ratio of live cells in fig. 8 exceeds 99% and the ratio of dead cells in fig. 9 is lower than 1% by using dead and live staining results, which shows that the biological adhesive has high biological safety and great clinical application potential.
Application example 1
(1) Weighing Tetra-PEG-NH 2 (purchased from Xiamen Sainumbange, product number 06020700212, molecular weight 2W) 0.1mg was added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) 0.1mg of Tetra-PEG-SC (purchased from Hebei Lihua biology, product number 65996-62-5, molecular weight 2W) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a second solution.
(3) 0.001mg of oxidized starch (purchased from Xiamen Sainungge, product number 06020702012, molecular weight 690.6) was weighed and added to 1mL of ultrapure water, and stirred at 4 ℃ for reaction for 5min to obtain a third solution.
(4) Measuring the first/second/third solution according to the ratio of 10:10:1 for 1s at room temperature to obtain the polyethylene glycol biological binder.
(5) And (3) taking the meniscus on the inner side of the knee joint of the dog as a meniscus injury model after the meniscus is transected, adding the polyethylene glycol biological adhesive obtained in the fourth step into a crack of the meniscus injury model, aligning two ends of the crack, and slightly fixing the crack for 5 seconds at room temperature to complete biological adhesive bonding.
Application comparative example 1
Taking a meniscus on the inner side of a dog knee joint, taking the meniscus as a meniscus injury model after the meniscus is transected, suturing the fracture of the meniscus injury model by using two 8-shaped surgical suture lines, and aligning two ends of the fracture for later use.
Comparative application example 2
Taking a meniscus on the inner side of a dog knee joint, transecting the meniscus to obtain a meniscus injury model, adding commercial 504 glue to a crack of the meniscus injury model, aligning two ends of the crack, and slightly fixing for 5 seconds at room temperature until biological glue is adhered for later use.
Comparative application example 3
(1) 0.1mg of Cellulose (purchased from Shanghai Yuan leaf, product number 9004-32-4, molecular weight 263.1976) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a first solution.
(2) Taking a meniscus on the inner side of a dog knee joint, taking the meniscus as a meniscus injury model after the meniscus is transected, adding a first solution into a crack of the meniscus injury model, aligning two ends of the crack, slightly fixing for 5 seconds at room temperature until biological glue is cemented for later use.
Application comparative example 4
(1) 0.1mg of Frbrin Glue (purchased from Hualan biology, china, product number S20020085) is weighed and added into 1mL of ultrapure water, and stirred and reacted for 5min at 4 ℃ to obtain a first solution.
(2) Taking a meniscus on the inner side of a dog knee joint, taking the meniscus as a meniscus injury model after the meniscus is transected, adding a first solution into a crack of the meniscus injury model, aligning two ends of the crack, slightly fixing for 5 seconds at room temperature until biological glue is cemented for later use.
Comparative application example 5
(1) 0.1mg of Gelatin (product No. 9000-70-8, available from Sigma, USA) was weighed and added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) Taking a meniscus on the inner side of a dog knee joint, taking the meniscus as a meniscus injury model after the meniscus is transected, adding a first solution into a crack of the meniscus injury model, aligning two ends of the crack, slightly fixing for 5 seconds at room temperature until biological glue is cemented for later use.
Comparative application example 6
(1) 0.1mg of Gel-MA (available from Yongqin spring, suzhou, product number EFL-GM-90, molecular weight 2W) and 0.001mg of LAP were weighed and added to 1mL of ultrapure water, and the mixture was stirred at 4 ℃ for 5min to obtain a first solution.
(2) Taking a meniscus on the inner side of a dog knee joint, taking the meniscus as a meniscus injury model after the meniscus is transected, adding a first solution into a crack of the meniscus injury model, aligning two ends of the crack, irradiating for 5s by using blue light, slightly fixing for 5s at room temperature until biological glue is cemented for later use.
In fig. 6 and 7 of the present invention, the correspondence relationship between english in the abscissa and the application examples and comparative examples is as follows:
Tetra-PEG: representative application example 1; suture: represents application comparative example 1 group; 504: representing application comparative example 2 group;
cellulose: representing application comparative example 3 group; fibre Glue: representative application comparative example 4 group; gelatin: representative application comparative example 5 group; gel-MA: comparative example 6 group is representative of the application.
As shown in figure 6, the meniscus adhesive property of the polyethylene glycol modified compound biological glue prepared in example 1 of the invention is excellent, after the meniscus is adhered in vitro, the meniscus is placed in a closed moist culture dish to simulate the moist environment of knee joint, and then is stretched vertically and continuously to transverse, the tensile strength of application example 1 can reach 600KPa, compared with the application comparative examples 1-6, the invention has the advantage of larger adhesive strength,
as shown in figure 7, the meniscus bonding prepared by the polyethylene glycol modified compound biological glue in the embodiment of the invention has excellent arthroscopic washing resistance, after the meniscus is bonded in vitro, the bonded meniscus is continuously washed by using an arthroscope, the washing resistance strength in the embodiment 1 can reach 30KPa, which is far higher than the water pressure strength of 10kPa required by clinical arthroscopic washing, and compared with the application of the groups in comparative examples 1-6, the meniscus bonding prepared by the polyethylene glycol modified compound biological glue has the advantages of higher arthroscopic washing resistance and larger clinical application potential.
Claims (10)
1. A preparation method of a polyethylene glycol biological adhesive is characterized by comprising the following steps: (1) Mixing Tetra-PEG-NH 2 Dissolving in ultrapure water to prepare a first solution with the concentration of 5-25 wt%, and placing on ice; (2) Dissolving Tetra-PEG-SC in ultrapure water to prepare a second solution with the concentration of 5-25 wt%, and placing on ice; (3) Dissolving oxidized starch in ultrapure water to obtain a third solution with a concentration of 0.01-0.2 wt%Placing on ice; (4) Mixing the first solution, the second solution and the third solution to obtain a biological adhesive; wherein the first solution: a second solution: the volume ratio of the third solution is 5-20:5-20:1.
2. the method of claim 1, wherein the first solution: a second solution: the volume ratio of the third solution is 5-15:5-15:1.
3. the method of claim 1, wherein: the concentration of the first solution is 5-20 wt%.
4. The method of claim 1, wherein: the concentration of the second solution is 5-20 wt%.
5. The method of claim 1, wherein: the concentration of the third solution is 0.05 to 0.15 wt%.
6. The method of claim 1, wherein: the porosity of the biological adhesive is 6-16 mu m, and the change of compression resilience at 25-85 ℃ is less than or equal to 1%.
7. The polyethylene glycol bioadhesive prepared by the preparation method according to any one of claims 1 to 6.
8. Use of a polyethylene glycol bioadhesive prepared by the preparation method according to any one of claims 1 to 6 for the preparation of a product for the treatment of meniscal injuries.
9. The application according to claim 8, characterized in that it comprises the following steps: s1, adding a biological adhesive to a damaged meniscus crack; s2, curing the biological adhesive.
10. The use according to claim 9, wherein the curing conditions comprise: the curing temperature is 4-27 ℃, and the curing time is 1s-5min.
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