Injectable hydrogel capable of rapidly stopping bleeding and preparation method thereof

Abstract

The invention discloses injectable hydrogel capable of rapidly stopping bleeding and a preparation method thereof. The injectable hydrogel is prepared from a natural high-molecular compound, a natural high-molecular polymer, an organic high-molecular polymer, a catechol-like organic compound, a cross-linking agent and ultrapure water. A natural high-molecular linear polymer is combined with an organic high-molecular polymer in a non-covalent bond manner to form a macromolecular polymer, and the macromolecular polymer is used as a main network skeleton of the hydrogel to provide strength support; the catechol-like organic compound and the natural high-molecular compound form a strong non-covalent effect in a polymer chain to enhance the strength, the hemostatic property, the antibacterial property, the adhesion and the self-healing property of the organogel; besides, under the action of the cross-linking agent, the catechol-like organic compound forms a free radical group to be subjected to free radical coupling with the macromolecular polymer, so that the effect of enhancing a hydrogel network is achieved, and meanwhile, hydrogen bonds, dipole-dipole interaction, static interaction and the like can be formed with polar functional groups on the surface. The hemostatic gel is rapid in hemostasis, simple to prepare, good in biocompatibility, good in antibacterial property, injectable and degradable.

Description

Technical Field

[0001] The invention belongs to the technical field of medical biomaterials, and more specifically relates to an injectable rapid hemostatic hydrogel and a preparation method thereof. Background Art

[0002] Uncontrolled bleeding caused by severe trauma cannot activate the body's normal coagulation cascade reaction. Uncontrolled bleeding remains the leading cause of death in military and civilian settings. Massive blood loss often leads to severe morbidity, including hypothermia, hypotension, and multiple organ dysfunction. Traumatic blood loss causes more than 2 million deaths worldwide each year, of which non-compressive bleeding accounts for about 42% of deaths.

[0003] In the case of severe wounds, although the body's intrinsic coagulation cascade process is usually unable to stop the massive bleeding, rapid and effective on-site hemostatic intervention using hemostatic materials is essential to save life and prevent bleeding complications in trauma patients. Because most deaths occur within the first hour after traumatic injury, early control of bleeding can effectively reduce mortality.

[0004] Although existing hemostatic technologies have achieved great success in controlling conventional traumatic bleeding, most hemostatic agents still have certain limitations for deep, narrow, irregularly shaped, and non-compressible fatal wounds with pressurized blood flow. Traditional wound sutures can be used clinically to close wounds to stop aortic bleeding, but are difficult to use in emergency situations, and tourniquets are less effective in most nodular bleeding sites (axilla, groin, neck).

[0005] Injectable biomedical materials can be formed in situ, deliver drugs in situ, and evenly incorporate therapeutic molecules and / or cells without surgery through narrow syringes. The injectability of biomedical materials can not only achieve rapid hemostasis at the site of trauma, but also promote rapid healing of the patient's wound by adhering to the site of trauma, thus playing an effective early control of acute traumatic bleeding. Injectable hydrogels are the most popular type of soft polymers for injectable biomedical materials. They can be flowing liquids before injection, and gel in situ through specific stimulation after injection to fill any irregular geometric shape. The composition and structure are highly similar to the extracellular matrix of animals, with viscoelasticity, diffusivity, and good biocompatibility. Therefore, it can provide simple mechanical support for the protection and regeneration of damaged tissues, load spatiotemporally controlled cells or therapeutic agents and deliver them to local recruitment and regulation of host cells.

[0006] With the help of weak intermolecular interactions, small molecules with specific structures can form aggregates of certain shapes. Small molecule gels have unique rheological behaviors and stimulus-responsive properties. They are widely used in many fields. Molecular self-assembly is closely related to its structure. Under the non-covalent bond interactions between molecules such as hydrogen bonding, van der Waals, free radical polymerization, π-π stacking, and electrostatic effects, they can form aggregates of various shapes, such as micelles, fibers, nanotubes, and helical ribbons. This structure that is aggregated by weak intermolecular forces is responsive to external stimuli.

[0007] Based on this, it is particularly important to provide an injectable rapid hemostatic hydrogel and a preparation method thereof. Summary of the invention

[0008] In order to solve the above problems in the prior art, the object of the present invention is to provide an injectable rapid hemostatic hydrogel and a preparation method thereof.

[0009] To achieve the above object, the technical solution of the present invention is:

[0010] An organic gel, which is made of an organic high molecular polymer and a natural high molecular compound, a cross-linking agent, a catechol-like organic compound and ultrapure water; the organic high molecular polymer is combined with the natural high molecular compound by a non-covalent bond to form a macromolecular polymer, which serves as the main network skeleton of the hydrogel to provide strength support;

[0011] The organic high molecular polymer is one, two or three of polyacrylic acid, polyvinyl alcohol, polyoxyethylene, polyvinyl chloride, polyacrylamide, poly-N-isopropylacrylamide, polyethylene glycol, polystyrene, polycaprolactone, polylactic acid, polyethylene, polyurethane, polyamino acid, polycarbonate and polyacetal; the natural high molecular compound is one, two or three of gelatin, hyaluronic acid, starch, bletilla striata polysaccharide, inulin, collagen, fibroin, mussel mucin, elastin, tannic acid, sodium alginate, cellulose, chitin, chitosan, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, acylated chitosan, carboxymethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxypropyl chitosan, alkylated chitosan, quaternized chitosan, amino oligosaccharides and derivatives thereof.

[0012] Furthermore, the catechol-like organic compound is: catechol, caffeic acid, folic acid, tannic acid, cinnamic acid, hydroxycinnamic acid, protocatechuic acid, parahydroxybenzoic acid esters, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, gentisic acid, gallic acid, pyrogallol acid, catechin, epicatechin, leucocyanidin, norepinephrine, epinephrine, dopamine, serotonin, lignans, coumarins, flavonols, flavanones, quercetin, anthocyanins, curcumin, resveratrol and their derivatives, and a combination of one, two or three thereof produces rapid hemostasis and strong adhesion effects.

[0013] The crosslinking agent is one, two or three of 1-ethyl-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide, polyisomethacrylate, N,N'-methylenebisacrylamide, ethylene glycol diacrylate, polyethylene glycol dimethacrylate, glutaraldehyde, acetic anhydride, 1,4-butanediol diglycidyl ether, divinyl sulfone, divinylbenzene and diisocyanate.

[0014] The preparation method of the organogel is carried out according to the following steps:

[0015] a. Mix one, two or three of the organic high molecular polymers: polyacrylic acid, polyvinyl alcohol, polyoxyethylene, polyvinyl chloride, polyacrylamide, poly-N-isopropylacrylamide, polyethylene glycol, polystyrene, polycaprolactone, polylactic acid, polyethylene, polyurethane, polyamino acid, polycarbonate and polyacetal with ultrapure water at a volume fraction of 10-50%, and mix them evenly in an ultrasonic oscillator for 5 minutes;

[0016] b. Adding the following natural polymer compounds with a mass concentration of 10-1000 g / L into the mixed solution obtained in step a: gelatin, hyaluronic acid, starch, bletilla striata polysaccharide, inulin, collagen, silk fibroin, mussel mucin, elastin tannic acid, sodium alginate, cellulose, chitin, chitosan, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, acylated chitosan, carboxymethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxypropyl chitosan, alkylated chitosan, quaternized chitosan, amino oligosaccharides and their derivatives, one, two or three thereof, and mixing evenly in an ultrasonic oscillator for 5 minutes. After fully mixing, standing at room temperature for 20 minutes;

[0017] c. Add one, two or three of the following catechol-like organic compounds with a mass concentration of 1-500 g / L into the mixed solution obtained in step b: catechol, caffeic acid, folic acid, tannic acid, cinnamic acid, hydroxycinnamic acid, protocatechuic acid, parahydroxybenzoic acid esters, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, gentisic acid, gallic acid, pyrogallol acid, catechin, epicatechin, leucocyanidin, norepinephrine, epinephrine, dopamine, serotonin, lignans, coumarins, flavonols, flavanones, quercetin, anthocyanins, curcumin, resveratrol and their derivatives, and mix or dissolve them evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir and mix evenly;

[0018] d. After all the substances in c are mixed evenly, add a cross-linking agent with a mass concentration of 0.1-10 g / L, which is one, two or three of 1-ethyl-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide, polyisomethacrylate, N,N'-methylenebisacrylamide, ethylene glycol diacrylate, polyethylene glycol dimethacrylate, glutaraldehyde, acetic anhydride, 1,4-butanediol diglycidyl ether, divinyl sulfone, divinylbenzene and diisocyanate, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix well under magnetic stirring, and then let stand at 4°C to fully cool;

[0019] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0020] Compared with the prior art, the beneficial effects of the present invention are:

[0021] The invention provides an injectable rapid hemostatic hydrogel and a preparation method thereof. The chemically synthesized rapid hemostatic organic gel is made of natural macromolecular compounds, natural macromolecular polymers, organic macromolecular polymers, catechol-like organic compounds, crosslinking agents and ultrapure water; the natural macromolecular linear polymers are combined with organic macromolecular polymers in a non-covalent bond manner to form macromolecular polymers, which provide strength support as the main network skeleton of the hydrogel; the catechol-like organic compounds and the natural macromolecular compounds form a strong non-covalent effect in the polymer chain to enhance the strength, hemostatic performance, antibacterial property, adhesion and self-healing performance of the organic gel; in addition, under the action of the crosslinking agent, the catechol-like organic compounds form free radical groups to perform free radical coupling with the macromolecular polymers, thereby enhancing the hydrogel network, and can also form hydrogen bonds, dipole-dipole, electrostatic and other interactions with polar functional groups on the surface.

[0022] Compared with the rapidly hemostatic, adhesive, degradable and self-healing injectable organogel described in the present invention, it has strong hemostatic performance, in situ injectability, perfect matching of irregular spatial geometry, and is compatible with good biocompatibility, good antibacterial performance, in vivo degradation, tight tissue adhesion, good mechanical properties and the like. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a diagram showing the rapid hemostasis effect of the present invention on rat liver scratches;

[0024] Figure 2 This is a diagram showing the rapid hemostasis effect of the present invention on rat liver defect;

[0025] Figure 3 This is a diagram for filling defective parts according to the present invention;

[0026] Figure 4 This is a diagram showing the antibacterial effect of the present invention on Staphylococcus aureus (S. aureus);

[0027] Figure 5 This is the organogel obtained by the present invention. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments:

[0029] like Figure 1-5 As shown,

[0030] Example 1

[0031] a. Mix polyvinyl alcohol and ultrapure water at a volume fraction of 20%, and mix evenly on a rotary mixer for 5 minutes;

[0032] b. Add 200 g / L hyaluronic acid to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0033] c. Add 20 g / L dopamine to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well, and mix evenly;

[0034] d. After all the substances in c are mixed evenly, add divinyl sulfone with a mass concentration of 0.5 g / L, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix thoroughly under magnetic stirring, and then let stand at 4°C to fully cool;

[0035] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0036] Example 2

[0037] a. Mix polyethylene glycol and ultrapure water at a volume fraction of 30%, and mix evenly in an ultrasonic oscillator for 5 minutes;

[0038] b. Add 100 g / L Bletilla striata polysaccharide and 200 g / L carboxymethyl chitosan to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0039] c. Add 20 g / L caffeic acid and folic acid to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well, and mix evenly;

[0040] d. After all the substances in c are mixed evenly, add 0.25 g / L 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 0.25 g / L N-hydroxysuccinimide, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix thoroughly under magnetic stirring, and then stand at 4°C to allow it to cool down sufficiently;

[0041] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0042] Example 3

[0043] a. Mix poly (N-isopropylacrylamide) and ultrapure water at a volume fraction of 25%, and mix evenly in an ultrasonic oscillator for 5 minutes;

[0044] b. Add 150 g / L silk fibroin and 150 g / L mussel mucin to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0045] c. Add quercetin at a mass concentration of 100 g / L to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to fully stir and mix evenly;

[0046] d. After all the substances in c are mixed evenly, add 0.8 g / L N,N'-methylenebisacrylamide, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix thoroughly under magnetic stirring, and then let stand at 4°C to fully cool;

[0047] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0048] Example 4

[0049] a. Mix polylactic acid and ultrapure water at a volume fraction of 10%, and mix evenly in an ultrasonic oscillator for 5 minutes;

[0050] b. Add 600 g / L gelatin to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0051] c. Add 30 g / L serotonin to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well, and mix evenly;

[0052] d. After all the substances in c are mixed evenly, add 0.3 g / L ethylene glycol diacrylate, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix thoroughly under magnetic stirring, and then let stand at 4°C to fully cool;

[0053] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0054] Example 5

[0055] a. Mix 10% polyacrylic acid and 10% polycaprolactone with ultrapure water, and mix them evenly in an ultrasonic oscillator for 5 minutes;

[0056] b. Add 500 g / L sodium alginate to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0057] c. Add 5 g / L gallic acid and 10 g / L coumarin to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well, and mix evenly;

[0058] d. After all the substances in c are mixed evenly, add 3 g / L 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 3 g / L N-hydroxysuccinimide, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix well under magnetic stirring, and then let stand at 4°C to fully cool;

[0059] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0060] Example 6

[0061] a. Mix polyacrylamide and ultrapure water at a volume fraction of 35%, and mix evenly in an ultrasonic oscillator for 5 minutes;

[0062] b. Add 100 g / L carboxymethyl cellulose, 50 g / L carboxymethyl chitin and 80 g / L carboxymethyl chitosan to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0063] c. Add 10 g / L resveratrol to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well and mix evenly;

[0064] d. After all the substances in c are mixed evenly, add 3 g / L 1,4-butanediol diglycidyl ether, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix thoroughly under magnetic stirring, and then let stand at 4°C to fully cool;

[0065] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0066] Example 7

[0067] a. Mix polyurethane with ultrapure water at a volume fraction of 45%, and mix evenly in an ultrasonic oscillator for 5 minutes;

[0068] b. Add 50 g / L carboxymethyl chitosan and 50 g / L quaternized chitosan to the mixed solution obtained in step a, mix evenly in an ultrasonic oscillator for 5 minutes, mix thoroughly, and let stand at room temperature for 20 minutes;

[0069] c. Add 2 g / L protocatechuic acid and 4 g / L curcumin to the mixed solution obtained in step b, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir well, and mix evenly;

[0070] d. After all the substances in c are mixed evenly, add 0.3 g / L N-hydroxysuccinimide and 0.15 g / L divinylbenzene, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix well under magnetic stirring, and then let stand at 4°C to fully cool;

[0071] e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

[0072] The invention provides a method for preparing an organogel. The chemically synthesized organogel capable of quickly stopping bleeding is made of natural macromolecular compounds, natural macromolecular polymers, organic macromolecular polymers, catechol-like organic compounds, crosslinking agents and ultrapure water. The natural macromolecular linear polymer is combined with the organic macromolecular polymer in a non-covalent bond manner to form a macromolecular polymer, which provides strength support as the main network skeleton of the hydrogel. The catechol-like organic compound and the natural macromolecular compound form a strong non-covalent effect in the polymer chain to enhance the strength, hemostatic performance, antibacterial property, adhesion and self-healing performance of the organogel. In addition, under the action of the crosslinking agent, the catechol-like organic compound forms a free radical group to carry out free radical coupling with the macromolecular polymer, which plays a role in strengthening the hydrogel network, and can also form hydrogen bonds, dipole-dipole, electrostatic and other interactions with polar functional groups on the surface.

[0073] Compared with the rapidly hemostatic, adhesive, degradable and self-healing injectable organogel described in the present invention, it has strong hemostatic performance, in situ injectability, perfect matching of irregular spatial geometry, and is compatible with good biocompatibility, good antibacterial performance, in vivo degradation, tight tissue adhesion, good mechanical properties and the like.

[0074] In order to verify the hemostatic property of the organogel of the present invention, a rat liver surface trauma model was first established for SD rats. The rats were anesthetized by inhalation of isoflurane. A small incision was made in the abdominal cavity of the rat liver, the liver was squeezed out, and the liver was scratched with a surgical blade, generally a straight-shaped wound (5mm), which was used as a non-compressible wound bleeding model. The prepared hydrogel was immediately injected into the straight-shaped wound. The rats in the blank control group bled profusely (2.85±0.22g), and the natural hemostasis time was 174±18s without external intervention. The blood loss in the organogel group was significantly reduced to 0.36±0.09g, and the hemostasis time was 36±1s. Subsequently, a rat liver internal non-compressible trauma bleeding model was established. The rats were anesthetized by inhalation of isoflurane. A small incision was made in the abdominal cavity of the rat liver, the liver was squeezed out, and a hole was punched in the liver with a puncher, generally a cylindrical wound (6×3mm 2 ), used as a non-compressible wound bleeding model. The prepared hydrogel was immediately inserted into the cylindrical wound. Rats in the blank control group bled profusely (3.68±0.28g), and the natural hemostasis time was 225±13s without external intervention. The blood loss in the organogel group was significantly reduced to 0.51±0.06g, and the hemostasis time was 40±2s. .

[0075] In addition, the preparation method of the organogel has the advantages of simple operation, readily available raw materials, low cost, environmental friendliness, simple preparation, easy application and promotion, and convenient carrying and storage. The organogel is suitable for tissue repair scaffolds, skin sensors, medical device coatings, drug / cell / gene or protein delivery carriers, trace substance detection substrates, etc.

[0076] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that are not conceived through creative work should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope defined in the claims.

Claims

1. An organogel, characterized in that: The organogel is made of organic high molecular polymers and natural high molecular compounds, cross-linking agents, catechol-like organic compounds and ultrapure water; the organic high molecular polymers are combined with natural high molecular compounds through non-covalent bonds to form macromolecular polymers, which provide strength support as the main network skeleton of the hydrogel; The organic high molecular polymer is one, two or three of polyacrylic acid, polyvinyl alcohol, polyoxyethylene, polyvinyl chloride, polyacrylamide, poly-N-isopropylacrylamide, polyethylene glycol, polystyrene, polycaprolactone, polylactic acid, polyethylene, polyurethane, polyamino acid, polycarbonate and polyacetal; the natural high molecular compound is one, two or three of gelatin, hyaluronic acid, starch, bletilla striata polysaccharide, inulin, collagen, fibroin, mussel mucin, elastin, tannic acid, sodium alginate, cellulose, chitin, chitosan, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, acylated chitosan, carboxymethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxypropyl chitosan, alkylated chitosan, quaternized chitosan, amino oligosaccharides and derivatives thereof.

2. The organogel according to claim 1, characterized in that The catechol-like organic compound is: a combination of one, two or three of catechol, caffeic acid, folic acid, tannic acid, cinnamic acid, hydroxycinnamic acid, protocatechuic acid, parahydroxybenzoic acid esters, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, gentisic acid, gallic acid, pyrogallol, catechin, epicatechin, leucocyanidin, norepinephrine, epinephrine, dopamine, serotonin, lignans, coumarins, flavonols, flavanones, quercetin, anthocyanins, curcumin, resveratrol and their derivatives.

3. The organogel according to claim 1, characterized in that The crosslinking agent is one, two or three of 1-ethyl-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide, polyisomethacrylate, N,N'-methylenebisacrylamide, ethylene glycol diacrylate, polyethylene glycol dimethacrylate, glutaraldehyde, acetic anhydride, 1,4-butanediol diglycidyl ether, divinyl sulfone, divinylbenzene and diisocyanate.

4. The method for preparing the organogel according to any one of claims 1 to 3, characterized in that: Follow these steps: a. Mix one, two or three of the organic high molecular polymers: polyacrylic acid, polyvinyl alcohol, polyoxyethylene, polyvinyl chloride, polyacrylamide, poly-N-isopropylacrylamide, polyethylene glycol, polystyrene, polycaprolactone, polylactic acid, polyethylene, polyurethane, polyamino acid, polycarbonate and polyacetal with ultrapure water at a volume fraction of 10-50%, and mix them evenly in an ultrasonic oscillator for 5 minutes; b. Adding the following natural polymer compounds with a mass concentration of 10-1000 g / L into the mixed solution obtained in step a: gelatin, hyaluronic acid, starch, bletilla striata polysaccharide, inulin, collagen, silk fibroin, mussel mucin, elastin tannic acid, sodium alginate, cellulose, chitin, chitosan, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, acylated chitosan, carboxymethyl chitosan, carboxymethyl chitosan, carboxyethyl chitosan, hydroxypropyl chitosan, alkylated chitosan, quaternized chitosan, amino oligosaccharides and their derivatives, one, two or three thereof, and mixing evenly in an ultrasonic oscillator for 5 minutes. After fully mixing, standing at room temperature for 20 minutes; c. Add one, two or three of the following catechol-like organic compounds with a mass concentration of 1-500 g / L into the mixed solution obtained in step b: catechol, caffeic acid, folic acid, tannic acid, cinnamic acid, hydroxycinnamic acid, protocatechuic acid, parahydroxybenzoic acid esters, methyl parahydroxybenzoate, ethyl parahydroxybenzoate, gentisic acid, gallic acid, pyrogallol acid, catechin, epicatechin, leucocyanidin, norepinephrine, epinephrine, dopamine, serotonin, lignans, coumarins, flavonols, flavanones, quercetin, anthocyanins, curcumin, resveratrol and their derivatives, and mix or dissolve them evenly in an ultrasonic oscillator at room temperature for 5 minutes to obtain a precursor solution, add a magnetic stirrer to stir and mix evenly; d. After all the substances in c are mixed evenly, add a cross-linking agent with a mass concentration of 0.1-10 g / L, which is one, two or three of 1-ethyl-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide, polyisomethacrylate, N,N'-methylenebisacrylamide, ethylene glycol diacrylate, polyethylene glycol dimethacrylate, glutaraldehyde, acetic anhydride, 1,4-butanediol diglycidyl ether, divinyl sulfone, divinylbenzene and diisocyanate, mix or dissolve evenly in an ultrasonic oscillator at room temperature for 5 minutes, mix well under magnetic stirring, and then let stand at 4°C to fully cool; e. After removing bubbles from the precursor solution obtained in step d, put it into a syringe and squeeze the fluid into the wound or defect site to form an organogel in situ.

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