CN115636960A - A kind of light-crosslinked silk fibroin hemostatic adhesive and preparation method thereof - Google Patents

Abstract

The invention discloses a photo-crosslinked silk fibroin hemostatic adhesive and a preparation method thereof, belonging to the fields of biological materials and biomedical applications. The hemostatic adhesive is prepared by uniformly mixing methacrylated silk fibroin, dopamine-modified alginic acid, calcium sulfate dihydrate and a photoinitiator at room temperature and protected from light, and then irradiating with ultraviolet light. The silk fibroin hemostatic adhesive prepared by the invention has the characteristics of high bonding strength, fast bonding speed, strong mechanical toughness, good biocompatibility and the like in a wet environment. Its operation is simple and easy to master, and there is no need for secondary operations such as stitch removal after surgery. The adhesive can be used for almost all trauma wounds. It has the functions of bonding tissues, covering wounds, filling defects and gaps, hemostasis, sealing, etc. It can be used as a The hemostatic adhesive material for tissues such as eyes has broad clinical application prospects.

Description

A kind of light-crosslinked silk fibroin hemostatic adhesive and preparation method thereof

technical field

The invention belongs to the field of biological materials and biomedical applications, and in particular relates to a photocrosslinked silk fibroin hemostatic adhesive and a preparation method thereof.

Background technique

Massive bleeding due to accidental injuries or clinical surgical procedures is one of the leading causes of death in the world population today. At present, the main means of clinical treatment of tissue bleeding is still surgical suture, which is closed by sutures, wires or closure nails. However, this treatment method is complicated to operate, takes a long time, requires a high level of operator, and forms a high stress concentration at the suture, which increases the pain of the patient. Under the "centipede"-like scar. In addition, in the repair of soft tissues such as the heart and liver, traditional suture materials are easy to cause secondary damage to the tissue, and some parenchyma tissues (such as lung, liver or kidney, etc.) are not suitable for suture repair, such as arteries Smaller tissue injuries such as defects also do not have enough space for conventional suturing, and even in tissues that can be sutured, hemostatic adhesive biomaterials may be required to achieve a better seal. With the rapid development of modern medicine, the clinical requirements for surgical methods and auxiliary materials are getting higher and higher, not only to reduce the pain of patients to the greatest extent, but also to restore the appearance perfectly while restoring the function. These requirements make The development of tissue adhesives has received extensive attention.

With the development of material science, a variety of adhesive materials for tissue adhesion have been developed, and currently developed tissue adhesives mainly include natural tissue adhesives and synthetic tissue adhesives. Common natural tissue adhesives include those based on fibrin, gelatin, collagen, polysaccharides, polypeptides, and the like. These adhesives have good biocompatibility, but generally have problems such as poor mechanical properties and flexibility, low adhesion strength (especially poor adhesion on wet tissue surfaces), slow hemostasis, and high production costs. Common synthetic adhesives include cyanoacrylates and polyethylene glycols. At present, the most widely used synthetic adhesive in clinical practice is cyanoacrylate adhesive, which has high adhesive strength, but poor biocompatibility and biodegradability, and toxic degradation products may cause foreign body reaction or even necrosis. In addition, the high stiffness of cyanoacrylate adhesives can hinder the physiological movement of elastic and soft tissues such as the lung, heart, and blood vessels, which is not conducive to tissue regeneration and biointegration, so this adhesive is limited to external (such as skin) repair of damage. Therefore, it is particularly necessary to develop a tissue adhesive with good biocompatibility and high adhesive strength in a wet environment in vivo.

Photocrosslinked hydrogels refer to the use of specific wavelengths of light to trigger the gelation of single-component hydrogel precursor solutions or composite hydrogel prepolymers to form solid hydrogel materials. The non-physical contact method of photocrosslinked hydrogel can effectively improve the spatiotemporal controllability of adhesive application, realize the regulation of the overall or local properties of the material, and reduce the impact of operating proficiency. In the fields of tissue engineering and biomedicine The hemostatic adhesive has broad application prospects. Silk fibroin is a natural protein derived from silkworms. It has good biocompatibility, suitable biodegradability and other biomedical properties, and has been approved by the FDA for use in medical devices. Currently, there are patent reports on the preparation of photocrosslinked silk fibroin hydrogels. In the Chinese invention patent "Preparation Method of Novel Methacrylic Anhydride Modified Silk Fibroin" with publication number CN 114773549 A, silk fibroin is modified with glycidyl methacrylate, and then treated with liquid nitrogen at low temperature, Freeze-dry to obtain liquid nitrogen-methacrylic fibroin, and prepare silk fibroin hydrogel through photocrosslinking. In the Chinese invention patent "a silk fibroin/hyaluronic acid composite hydrogel, preparation method and application" with the publication number CN114524953 A, the silk fibroin and hyaluronic acid are used as raw materials, and the silk fibroin is passed through methacrylic acid Glycidyl ester modification, hyaluronic acid is modified by methacrylic anhydride, the modified product is mixed and dissolved in deionized water, and ultraviolet light is used to drive cross-linking to obtain a hydrogel. However, due to the lack of wet-state adhesion functional groups and multiple intermolecular interactions of the above-mentioned methacrylated silk fibroin hydrogels, they are not compatible with organisms in wet-state environments (water and blood, etc.). The adhesive strength of the surface is low, the mechanical toughness is poor, and it cannot adapt to the dynamic adhesion of the tissue interface in a wet physiological environment.

Therefore, the present invention uses methacrylated silk fibroin as a matrix material, adds dopamine-grafted alginic acid, calcium ions, and a photoinitiator, and uses ultraviolet light to irradiate the mixed solution to quickly cross-link and polymerize within 1-60 seconds. , in the presence of chemical covalent bond cross-linking and metal ion bond dynamic cross-linking, silk fibroin hemostatic adhesion with strong mechanical toughness, high bonding strength in wet environment, fast forming bonding speed, and good biocompatibility agent. At present, there is no relevant research report in relevant patents at home and abroad.

Contents of the invention

The purpose of the present invention is to provide a tissue hemostatic adhesive with good biocompatibility, high bonding strength in a wet environment in the body, fast forming and bonding speed, and strong mechanical toughness, aiming at the deficiencies of the prior art. The invention overcomes the problems of the existing tissue hemostatic adhesives such as slow forming speed, low bonding strength, poor biocompatibility, and poor mechanical toughness under the physiological environment in vivo, and the prepared silk fibroin hemostatic adhesive can be used in almost For all trauma wounds, it has the functions of bonding tissues, covering wounds, filling tissue defects and gaps, hemostasis, and sealing.

To achieve the above object, the present invention adopts the following technical solutions:

A preparation method of a light-crosslinked silk fibroin hemostatic adhesive: take methacrylated silk fibroin as a matrix, add dopamine-modified alginic acid, calcium sulfate dihydrate and photoinitiator, and stir evenly at room temperature in the dark , rapid cross-linking and polymerization within 60 seconds of the mixed solution under ultraviolet light irradiation, in the presence of chemical covalent bond cross-linking and metal ion bond dynamic cross-linking, silk fibroin with strong mechanical properties and high adhesion performance in wet physiological environment is obtained Protein hemostatic adhesive.

Further, a method for preparing a photocrosslinked silk fibroin hemostatic adhesive specifically comprises the following steps:

(1) Preparation of methacrylated silk fibroin solution: after deionized water was heated to boiling, Na ₂ CO ₃ and silk were added to degumming silk; after washing and drying, the dried degummed silk was used Dissolve lithium bromide solution to obtain silk fibroin solution, then add glycidyl methacrylate to modify silk fibroin, and then dialyze with deionized water; the dialyzed solution is centrifugally filtered to obtain methacrylated silk fibroin Protein solution; the mass percent concentration of the silk fibroin solution is between 0.1%-50% or between 0.01 mg/mL-500 mg/mL.

(2) Preparation of dopamine-modified alginic acid: fully dissolve sodium alginate in deionized water, then add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinyl Imine, activated carboxyl group; after the activation, add dopamine hydrochloride to react overnight, and control the pH of the reaction system ≤ 5 during the reaction; the obtained solution is dialyzed, freeze-dried to obtain a white spongy substance, which is dissolved in deionized water to obtain dopamine-modified seaweed Acid solution; the mass percent concentration of the dopamine-modified alginic acid solution is between 0.1%-50% or between 0.01 mg/mL-500 mg/mL.

(3) Photocrosslinked silk fibroin hemostatic adhesive: the dopamine-modified alginic acid solution prepared in step (2), calcium sulfate dihydrate and photoinitiator LAP were dissolved in step (1) at room temperature and protected from light. In the methacrylated silk fibroin solution, stir evenly in the dark to obtain a precursor solution; the precursor solution is quickly cross-linked and polymerized within 1 minute under ultraviolet light irradiation to obtain a strong mechanical properties, wet physiological environment Silk fibroin hemostatic adhesive with high adhesion performance. The mass ratio of added dopamine-modified alginic acid to methacrylated silk fibroin is 100:1-1:100. The wavelength of ultraviolet light used for the ultraviolet irradiation is 200-400 nanometers.

The photocrosslinked silk fibroin hemostatic adhesive prepared by the above preparation method can be used as a hemostatic adhesive material for skin, organs, blood vessels, nerves, muscles, mucous membranes, bones, joints, eyes and other tissues, and can realize wet state Rapid adhesion in the environment (including water, PBS buffer, blood environment), the adhesion time is within 60 seconds; it has good biocompatibility and strong adhesion, and can be used for almost all trauma wounds, with adhesion tissue, covering wounds, filling tissue defects and gaps, hemostasis, sealing, etc.

Significant advantage of the present invention is:

(1) The present invention uses silk fibroin with excellent biocompatibility as the main component of the adhesive to prepare methacrylated silk fibroin, adding dopamine-modified alginic acid, calcium sulfate dihydrate and photoinitiator . Under ultraviolet light irradiation, methacrylated silk fibroin forms chemical covalent bond crosslinks and induces the conformational transformation of silk fibroin molecules into β-sheet, and a dynamic metal ion chelation is formed between alginic acid molecules and metal calcium ions The cooperative effect, the polyphenol-metal ion bond between the alginate-grafted dopamine group and the metal calcium ion, endows the material with excellent mechanical toughness. Compared with traditional methacrylated silk fibroin photocrosslinked hydrogels, the mechanical toughness of the present invention is significantly enhanced. However, traditional methacrylated silk fibroin photocrosslinked hydrogels only rely on methacrylated silk fibroin to form chemical covalent bond crosslinks, without introducing molecules such as ionic bonds with dynamic energy dissipation mechanisms. Interaction between them leads to poor mechanical toughness.

(2) The dopamine group grafted with alginic acid can be tightly combined with the wet biological tissue surface. Based on the synergistic effect of chemical covalent bond cross-linking and metal ion bond dynamic cross-linking, it significantly improves the hemostatic adhesive in the wet state. Adhesive strength to the surface of organisms in the environment, endowed with excellent wet adhesion ability. The bonding strength of the present invention to tissues under wet environment (including water, PBS buffer solution and blood environment) is above 400 kPa. However, the traditional methacrylated silk fibroin photocrosslinked hydrogel lacks wet-state adhesion functional groups, and the adhesion strength to the surface of the organism is poor in a wet environment (water and blood, etc.) ( The adhesive strength is below 30 kPa), which cannot adapt to the dynamic adhesion of the tissue interface. Therefore, the present invention is more suitable for the humid environment of massive bleeding of damaged tissue, has good tissue hemostatic adhesion potential, and can be used as a hemostatic adhesive for tissues such as skin, organs, blood vessels, nerves, muscles, mucous membranes, bones, joints, eyes, etc. Material,

(3) The light-triggered non-invasive cross-linking method in the present invention can realize rapid cross-linking within 1-60 seconds under ultraviolet light irradiation, and the principle of rapid cross-linking is attributed to the formazan in methacrylated silk fibroin. Fast photocrosslinkable reaction of acrylate groups, fast metal ion chelation between alginic acid and metal calcium ions, fast polyphenol-metal ion bonds between dopamine groups and metal calcium ions, and silk fibroin Rapid electrostatic interaction between the molecule and the dopamine group. The invention effectively avoids environmental hazards caused by long-term ultraviolet light irradiation, and improves the space-time controllability of applying the hemostatic adhesive and the adaptability of human tissues. .

(4) The tissue adhesive in the present invention can bond wounds of different sizes and shapes according to the needs of patients, and the feature of in-situ curing provides convenience for clinical application.

(5) The raw materials of the present invention are all derived from natural compounds, so they have good biocompatibility.

(6) The present invention has the advantages of simple operation, easy batch production, etc., and has good industrialization prospects.

Description of drawings

Fig. 1 Macroscopic effect diagram of underwater forming adhesion of photocrosslinked silk fibroin hemostatic adhesive.

Fig. 2 Hemostasis effect of photo-crosslinked silk fibroin hemostatic adhesive on wounded heart tissue.

Detailed ways

In order to verify the feasibility of the design, the technical solution of the present invention will be further described below in conjunction with specific implementation methods, but the application of the present invention is not limited thereto.

Example 1

(1) After heating 1 L of deionized water to boiling, add 5.3 g of sodium carbonate and wait until it is fully dissolved. Put 40 g of silkworm silk into it, and degumming process at 100 °C for 30 minutes. The boiled silk was taken out, washed thoroughly with deionized water, and dried in an oven at 60 °C. The dried degummed silk was added to 9.3M LiBr solution and dissolved at 60 °C for 1 h to obtain a silk fibroin solution, then 12 mL of glycidyl methacrylate was added to the silk fibroin solution, and reacted at 60 °C for 3 h. The whole reaction process was protected from light. The reacted solution was put into a dialysis bag, and dialyzed with deionized water for 7 days, and the whole process of dialysis was protected from light. The dialyzed solution was filtered and centrifuged, and concentrated to obtain a methacrylated silk fibroin solution with a mass fraction of about 25%.

(2) Add 400mg of sodium alginate and 50ml of deionized water into the round bottom flask, fully dissolve under magnetic stirring. Subsequently, 383.4 mg of EDC and 230.18 mg of NHS were added to activate the carboxyl group and adjust the pH of the reaction solution to 5. Add 189.62 mg of dopamine hydrochloride, and stir overnight for 12 hours. After the reaction, the resulting solution was put into a dialysis bag and dialyzed for 24 h. After the dialysis, the resulting solution was freeze-dried to obtain a white spongy substance, which was dissolved in deionized water to obtain a dopamine-modified alginic acid solution with a mass fraction of about 5%.

(3) Add 1 ml of dopamine-modified alginic acid solution and 0.1 ml of calcium sulfate dihydrate solution with a concentration of 0.75 M to 5 ml of methacrylated silk fibroin solution at room temperature, and add The final concentration of the LAP initiator is 0.03wt%, and it is stirred and mixed to obtain a binder precursor solution. The adhesive precursor solution is rapidly cross-linked within 5 seconds under ultraviolet light (wavelength: 365 nanometers) to obtain an adhesive.

The adhesive is used for hemostatic adhesion of soft tissues such as the heart, and has excellent wet adhesion effect. The adhesion strength of the adhesive in a wet environment (water) is 650 KPa, and the toughness is 80 KJ/m ³ . Fig. 1 is a macroscopic effect diagram of underwater forming adhesion of photocrosslinked silk fibroin hemostatic adhesive. The invention can realize rapid crosslinking after ultraviolet light irradiation. Even under water, the hydrogel still exhibits excellent cross-linking speed and adhesion effect, and can firmly adhere to the surface of the glass substrate under water and withstand strong water flow. Fig. 2 is a graph showing the hemostatic effect of the photocrosslinked silk fibroin hemostatic adhesive on wounded heart tissue. The invention can realize rapid hemostasis of wounded tissue on the surface of the beating heart and can withstand intense mechanical movement. However, the traditional methacrylated silk fibroin photocrosslinked hydrogel (Comparative Example 1) has poor adhesion strength to the surface of organisms under water due to the lack of wet-state adhesion functional groups. The strength is 28 KPa, and the toughness is 4.5 KJ/m ³ .

Example 2

(1) After heating 2 L of deionized water to boiling, add 8.48 g of sodium carbonate and wait until it is fully dissolved. Put 20 g of silkworm silk into it, and degumming process at 100 °C for 30 minutes. The boiled silk was taken out, washed thoroughly with deionized water, and dried in an oven at 50 °C. The dried degummed silk was added to a 9.3M LiBr solution and dissolved at 60 °C for 3 h to obtain a silk fibroin solution, then 6 mL of glycidyl methacrylate was added to the silk fibroin solution, and reacted at 60 °C for 3 h. The whole reaction process was protected from light. The reacted solution was put into a dialysis bag, and dialyzed with deionized water for 7 days, and the whole process of dialysis was protected from light. The dialyzed solution was filtered and centrifuged, and concentrated to obtain a methacrylated silk fibroin solution with a mass fraction of about 5%.

(2) Add 800 mg of sodium alginate and 50 ml of deionized water into the round bottom flask, fully dissolve under magnetic stirring. Subsequently, 750 mg EDC and 460 mg NHS were added to activate the carboxyl group and adjust the pH of the reaction solution to 5. Add 400 mg of dopamine hydrochloride and stir overnight for 12 hours. After the reaction, the resulting solution was put into a dialysis bag and dialyzed for 24 h. After the dialysis, the resulting solution was freeze-dried to obtain a white spongy substance, which was dissolved in deionized water to obtain a dopamine-modified alginic acid solution with a mass fraction of about 15%.

(3) Add 7 ml of dopamine-modified alginic acid solution and 0.3 ml of 0.75 M calcium sulfate dihydrate solution to 10 ml of methacrylated silk fibroin solution at room temperature, and mix well Finally, LAP initiator with a final concentration of 0.02wt% was added, stirred and mixed to obtain a binder precursor solution. The adhesive precursor solution is rapidly cross-linked within 20 seconds under ultraviolet light (wavelength: 400 nanometers) to obtain an adhesive.

The adhesive is used for sealing and bonding soft tissues such as stomach and intestine, and has excellent wet-state adhesion effect. The adhesion strength of the adhesive in a wet environment (water) is 410 KPa, and the toughness is 50 KJ/m ³ .

Example 3

(1) After heating 10 L of deionized water to boiling, add 50 g of sodium carbonate and wait until it is fully dissolved. Put 400 g silkworm silk into it, and degumming process at 100 °C for 30 minutes. The boiled silk was taken out, washed thoroughly with deionized water, and dried in an oven at 70 °C. The dried degummed silk was added to 9.3M LiBr solution and dissolved at 60 °C for 6 h to obtain a silk fibroin solution, then 150 mL glycidyl methacrylate was added to the silk fibroin solution, and reacted at 60 °C for 6 h. The whole reaction process was protected from light. The reacted solution was put into a dialysis bag, and dialyzed with deionized water for 5 days, and the whole process of dialysis was protected from light. The dialyzed solution was filtered and centrifuged to obtain a methacrylated silk fibroin solution with a mass fraction of about 50% after concentration.

(2) Add 2 g of sodium alginate and 50 ml of deionized water into the round-bottom flask, and fully dissolve it under magnetic stirring. Subsequently, 1.5 g of EDC and 1 g of NHS were added to activate the carboxyl group and adjust the pH of the reaction solution to 5. Add 1.5 g of dopamine hydrochloride and stir overnight for 12 hours. After the reaction, the resulting solution was put into a dialysis bag and dialyzed for 24 h. After the dialysis, the resulting solution was freeze-dried to obtain a white spongy substance, which was dissolved in deionized water to obtain a dopamine-modified alginic acid solution with a mass fraction of about 50%.

(3) Add 10 ml of dopamine-modified alginic acid solution and 3 ml of 0.75 M calcium sulfate dihydrate solution to 30 ml of methacrylated silk fibroin solution at room temperature, and mix well Finally, LAP initiator with a final concentration of 0.05wt% was added, stirred and mixed to obtain a binder precursor solution. The adhesive precursor solution is rapidly cross-linked within 50 seconds under ultraviolet light (wavelength: 250 nanometers) to obtain an adhesive.

The adhesive is used for hemostatic adhesion of soft tissues such as skin, blood vessels, muscles, liver, etc., and has excellent wet adhesion effect. The adhesion strength of the adhesive in a wet environment (water) is 520 KPa, and the toughness is 70 KJ/m ³ .

Comparative example 1 (traditional methacrylated silk fibroin photocrosslinked hydrogel)

(1) Same as step (1) of Example 1;

(2) Add LAP initiator with a final concentration of 0.03wt% to 5ml of methacrylated silk fibroin solution at room temperature and avoid light, and stir to obtain a precursor solution. The precursor solution is irradiated and crosslinked under ultraviolet light (wavelength: 365 nanometers) to obtain an adhesive.

Comparative example 2 (silk fibroin is not methacrylated)

(1) After heating 1 L of deionized water to boiling, add 5.3 g of sodium carbonate and wait until it is fully dissolved. Put 40 g of silkworm silk into it, and degumming process at 100 °C for 30 minutes. The boiled silk was taken out, washed thoroughly with deionized water, and dried in an oven at 60 °C. The dried degummed silk was added to 9.3M LiBr solution and dissolved at 60 °C for 1 h to obtain a silk fibroin solution. The reacted solution was put into a dialysis bag and dialyzed with deionized water for 7 days. The whole dialysis process was protected from light. . The dialyzed solution was filtered and centrifuged, and concentrated to obtain a silk fibroin solution with a mass fraction of about 25%.

(2) Same as step (2) of Example 1;

(3) Except for the different cross-linking time by ultraviolet light, the rest are the same as step (3) of Example 1.

Comparative example 3 (without dopamine-modified alginic acid)

(1) Same as step (1) of Example 1;

(2) Add 0.1 ml of calcium sulfate dihydrate solution with a concentration of 0.75 M to 5 ml of methacrylated silk fibroin solution at room temperature, and add LAP with a final concentration of 0.03 wt% after mixing Initiator, stirring and mixing to obtain a binder precursor solution. The adhesive precursor solution is cross-linked under ultraviolet light (wavelength: 365 nanometers) to obtain an adhesive.

Comparative example 4 (the added alginic acid is not modified by dopamine)

(1) Same as step (1) of Example 1;

(2) Add sodium alginate and deionized water into the round bottom flask, fully dissolve under magnetic stirring, and obtain an alginic acid solution with a mass fraction of about 5%;

(3) Add 1 ml of alginic acid solution and 0.1 ml of 0.75 M calcium sulfate dihydrate solution to 5 ml of methacrylated silk fibroin solution at room temperature, and add the final concentration after mixing. 0.03wt% LAP initiator, stirred and mixed to obtain a binder precursor solution. The adhesive precursor solution is cross-linked under ultraviolet light (wavelength: 365 nanometers) to obtain an adhesive.

The wet adhesion of the comparative example 2-4 gel group (silk fibroin not methacrylated, not dopamine-modified alginic acid added, added alginic acid not dopamine-modified) prepared using the single factor principle Intensity and modulus of toughness are worse than Example 1 of the present invention.

The above descriptions are only examples of the present invention, and all equivalent changes and modifications made according to the scope of the patent application of the present invention shall fall within the scope of the present invention.

Claims (9)

1. A preparation method of a photo-crosslinking silk fibroin hemostatic adhesive is characterized by comprising the following steps: the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property in a wet physiological environment is obtained by taking methacrylic acid esterified silk fibroin as a matrix, adding dopamine modified alginic acid, calcium sulfate dihydrate and a photoinitiator, uniformly stirring at room temperature in a dark place, quickly crosslinking and polymerizing the mixed solution within 60 seconds under the irradiation of ultraviolet light, and under the existence of chemical covalent bond crosslinking and metal ionic bond dynamic crosslinking.

2. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 1, characterized in that: the method specifically comprises the following steps:

(1) Preparation of methacrylated silk fibroin solution: heating deionized water to boil, adding Na ₂ CO ₃ And silk, degumming the silk; after washing and drying, dissolving the dried degummed silk by using a lithium bromide solution to obtain a silk fibroin solution, then adding glycidyl methacrylate to modify the silk fibroin, and then dialyzing by using deionized water; centrifuging and filtering the dialyzed solution to obtain a methacrylic acid esterified silk fibroin solution;

(2) Preparation of dopamine-modified alginic acid: fully dissolving sodium alginate in deionized water, and then adding 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide and N-hydroxysuccinimide to activate carboxyl; after the activation, adding dopamine hydrochloride to react overnight, and controlling the pH value of a reaction system to be less than or equal to 5 in the reaction process; dialyzing the obtained solution, carrying out freeze drying treatment to obtain a white spongy substance, and dissolving the white spongy substance with deionized water to obtain a dopamine-modified alginic acid solution;

(3) Photo-crosslinked silk fibroin hemostatic adhesive: dissolving the dopamine-modified alginic acid solution prepared in the step (2), calcium sulfate dihydrate and a photoinitiator in the methacrylated silk fibroin solution prepared in the step (1) at room temperature in a dark place, and uniformly stirring in the dark place to obtain a precursor solution; the precursor solution is rapidly crosslinked and polymerized within 60 seconds under the irradiation of ultraviolet light to obtain the silk fibroin hemostatic adhesive with strong mechanical property and high adhesion property under a wet physiological environment.

3. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the mass percentage concentration of the methacrylated silk fibroin solution in the step (1) is 0.1-50%.

4. The method for preparing the photo-crosslinking silk fibroin hemostatic adhesive according to claim 2, wherein: the mass percentage concentration of the dopamine modified alginic acid solution in the step (2) is 0.1-50%.

5. The method for preparing the photo-crosslinking silk fibroin hemostatic adhesive according to claim 2, wherein: the mass ratio of the dopamine-modified alginic acid to the methacrylated silk fibroin in the step (3) is 100.

6. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the ultraviolet light irradiated in the step (3) has the wavelength of 200-400 nanometers.

7. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the ultraviolet light irradiation time in the step (3) is 1-60 seconds.

8. The preparation method of the photo-crosslinked silk fibroin hemostatic adhesive according to claim 2, characterized in that: the photoinitiator is photoinitiator LAP.

9. A photocrosslinked silk fibroin hemostatic adhesive made by the method of any one of claims 1~8.

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