Self-healing, injectable photocrosslinked double-network hydrogel and preparation method thereof

Abstract

The application discloses a self-healing and injectable photocrosslinking double-network hydrogel and a preparation method thereof. The preparation method comprises the following steps: firstly, glycidyl methacrylate solution is used to perform methacryl modification on silk fibroin; then, sodium periodate solution is used to make dextran perform an oxidation reaction to generate oxidized dextran; and finally, a double-network hydrogel is formed through Schiff base crosslinking reaction between amino groups in the modified silk fibroin and aldehyde groups in the oxidized dextran. The double-network hydrogel prepared by the method has a more compact structure, and thus, the double-network hydrogel has a series of excellent performances, such as safety, injectability, good adhesion, good mechanical properties, self-healing property and drug release performance after drug loading.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, specifically to a self-healing, injectable photocrosslinked dual-network hydrogel and its preparation method. Background Technology

[0002] Wound healing is a highly organized biological process, mainly consisting of four overlapping stages: hemostasis, inflammation regulation, cell proliferation, and tissue remodeling. However, due to the unique local microenvironment at the wound site in diabetic patients, such as chronic inflammation, poor angiogenesis, and epithelial dysfunction, diabetic wounds may heal slowly or even fail to heal, potentially leading to amputation or even threatening life.

[0003] Currently, the main methods for wound treatment in diabetic patients include wound dressings, hyperbaric oxygen therapy, negative pressure wound therapy, growth factor-based therapy, and stem cell therapy. However, apart from wound dressings, the other methods are still the primary treatment due to their high cost, instability, and lack of safety evaluation methods.

[0004] Hydrogels currently hold the most promising development prospects in medical dressings. As a hydrophilic three-dimensional cross-linked network system, hydrogels offer multiple advantages in medical dressings. Injectable hydrogels, with their shear-thinning properties, tunable physical and chemical properties, controllable degradation performance, high water content, and ability to be delivered via minimally invasive methods, offer even greater advantages for wounds and other conditions. Currently, they have significant research and application value in fields such as 3D cell culture, wound dressings, drug delivery, tissue engineering, and regenerative medicine.

[0005] Silk fibroin is a natural high-molecular-weight protein extracted from silkworm silk. It possesses biocompatibility and biodegradability, and is composed of fibroin and sericin. Silk fibroin includes one hydrophobic peptide chain (H chain) and one hydrophilic peptide chain (L chain). The unique amino acid sequences of the H and L chains allow it to form various protein secondary conformations. By regulating the secondary structure of silk fibroin, various properties of silk fibroin materials can be effectively controlled. Silk fibroin produced from silkworms has been approved by the FDA for drug delivery and surgical suture applications. Due to its excellent biocompatibility, adjustable biodegradability, and mechanical properties, it has been used in various biomedical applications.

[0006] Currently, to improve the shortcomings of single-network hydrogels composed of silk fibroin, such as excessively large pores after hydrogel formation, poor gelation performance, long gelation time, poor gel adhesion, poor mechanical properties, and easy breakage, the main improvement method is to add chemical cross-linking agents. Although this method can enhance the performance of the hydrogel, the residual chemical cross-linking agents lead to a certain degree of toxicity, thereby reducing the biocompatibility of the hydrogel. Therefore, there is a need to develop a safe, non-toxic medical dressing with better gelation and mechanical properties to increase its practicality. Summary of the Invention

[0007] Therefore, the purpose of this invention is to provide a self-healing, injectable photocrosslinked dual-network hydrogel and its preparation method, wherein the hydrogel has good self-healing properties, good mechanical properties and high safety.

[0008] The above-mentioned objective of this invention is achieved through the following technical solution:

[0009] One aspect of the present invention is to provide a method for preparing a self-healing, injectable photocrosslinked dual-network hydrogel, comprising the following steps:

[0010] (1) Preparation of modified silk fibroin

[0011] Degummed silk fibroin fibers were dissolved in lithium bromide aqueous solution and stirred at 65°C. While stirring, glycidyl methacrylate solution was added dropwise for methacrylation modification. After stirring for 5-8 hours, a mixed solution was obtained. The mixed solution was dialyzed and freeze-dried to obtain sponge-like modified silk fibroin.

[0012] (2) Preparation of oxidized dextran

[0013] Add dextran to deionized water, then add sodium periodate solution dropwise to the dextran solution, stir at room temperature in the dark for 3-6 hours, then add ethylene glycol to stop the reaction, and then dialyze and freeze dry to obtain oxidized dextran.

[0014] (3) Mix the oxidized dextran solution with the modified silk fibroin solution, then add the photoinitiator solution to mix and obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0015] In one alternative embodiment, the mass ratio of the silk fibroin fiber to the glycidyl methacrylate is 10:3.

[0016] In one alternative embodiment, the mass ratio of the dextran to the sodium periodate is 2.5:1.

[0017] In one alternative embodiment, the mass ratio of the modified silk fibroin to oxidized dextran is 3:(0.5-9).

[0018] In one optional embodiment, the degree of oxidation substitution of the oxidized dextran is 20%.

[0019] In an optional embodiment, the method for preparing the photocrosslinked dual-network hydrogel according to claim 1 is characterized in that, in step (1), the concentration of the lithium bromide aqueous solution is 8-10 mol / L; and the concentration of the glycidyl methacrylate solution is 300-400 mmol / L.

[0020] In one alternative embodiment, in step (2), the mass concentration of the sodium periodate solution is 20%.

[0021] In an optional embodiment, in step (3), the mass-volume concentration of the modified silk fibroin aqueous solution is 10-20%; and the mass-volume concentration of the oxidized dextran aqueous solution is 5-10%.

[0022] In an optional embodiment, in step (3), the mass-volume concentration of the photoinitiator solution is 0.1-0.2%.

[0023] Another aspect of the present invention is to provide a photocrosslinked dual-network hydrogel, wherein the hydrogel is prepared by the above-described preparation method.

[0024] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0025] This invention first modifies silk fibroin by methacrylylation to introduce double bonds, which improves its solubility. Then, it oxidizes dextran with sodium periodate to introduce aldehyde groups. After mixing the modified silk fibroin and the oxidized dextran, the amino groups in the modified silk fibroin and the aldehyde groups in the oxidized dextran undergo a Schiff base cross-linking reaction to form a double-network hydrogel. This makes the hydrogel structure more compact, giving it a series of excellent properties, including safety, injectability, good adhesion, good mechanical properties, self-healing properties, and sustained-release properties after drug loading. Attached Figure Description

[0026] Figure 1 Image of the photocrosslinked dual-network hydrogel of this invention;

[0027] Figure 2 SEM images of the hydrogel after vacuum freeze-drying provided for embodiments and comparative examples of the present invention;

[0028] Figure 3 An image showing two pieces of hydrogel that can heal each other, provided as an embodiment of the present invention;

[0029] Figure 4 Images of the hydrogel being injected into water according to embodiments of the present invention;

[0030] Figure 5 The rheological behavior of the hydrogel provided in the embodiments of the present invention;

[0031] Figure 6 The rheometer behavior of dextran with different degrees of oxidation substitution and silk fibroin mixed at different mass ratios according to the present invention;

[0032] Figure 7 The hemolytic activity of the hydrogel provided in the embodiments of the present invention. Detailed Implementation

[0033] To enable those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present application, and not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present application.

[0034] Example 1

[0035] (1) Preparation of modified silk fibroin

[0036] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0037] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0038] (2) Preparation of oxidized dextran

[0039] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (20% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 20%.

[0040] (3) Mix 5 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.1% LAP (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0041] Example 2

[0042] (1) Preparation of modified silk fibroin

[0043] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0044] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0045] (2) Preparation of oxidized dextran

[0046] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (20% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 20%.

[0047] (3) Mix 15 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.01% LAP (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0048] Example 3

[0049] (1) Preparation of modified silk fibroin

[0050] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0051] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0052] (2) Preparation of oxidized dextran

[0053] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (20% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 20%.

[0054] (3) Mix 45 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.01% LAP (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0055] Example 4

[0056] (1) Preparation of modified silk fibroin

[0057] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0058] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0059] (2) Preparation of oxidized dextran

[0060] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (40% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 40%.

[0061] (3) Mix 5 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.01% LAP (phenyl (2,4,6-trimethylbenzoyl) lithium phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0062] Example 5

[0063] (1) Preparation of modified silk fibroin

[0064] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0065] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0066] (2) Preparation of oxidized dextran

[0067] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (40% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 40%.

[0068] (3) Mix 15 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.01% LAP (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0069] Example 6

[0070] (1) Preparation of modified silk fibroin

[0071] Take silkworm cocoons, cut them into pieces, add 2L of 5g / L Na2CO3 aqueous solution to an induction cooker pot, soak the cut silkworm cocoons in it, boil gently for 30 minutes, then soak and rinse with plenty of deionized water at least five times. Repeat the above operation three times, wring them dry, tear them into strips, and dry them in a 37℃ oven to obtain degummed silk fibroin fibers.

[0072] Prepare 50 mL of 9 M (40 g) lithium bromide aqueous solution by volumetric flask dilution. Dissolve 10 g of degummed silk fibroin fiber in the lithium bromide aqueous solution and stir at 65 °C. While stirring, add 2.5 mL (350 mM) glycidyl methacrylate solution dropwise for methacrylation modification. Stir for 6 h to obtain a mixed solution. Dialyze and freeze-dry the mixture to obtain sponge-like modified silk fibroin.

[0073] (2) Preparation of oxidized dextran

[0074] Take 2.5g of dextran and add it to 50mL of deionized water to obtain a dextran solution. Then, add 5mL (40% w / v) sodium periodate solution dropwise to the dextran solution. Stir at room temperature in the dark for 4h. Then add 2mL of ethylene glycol to stop the reaction. After dialyzing and lyophilization, oxidized dextran can be obtained. The degree of oxidation substitution of oxidized dextran is 40%.

[0075] (3) Mix 45 mL (10% w / v) of oxidized dextran solution with 10 mL (15% w / v) of modified silk fibroin solution, and then add 10 mg of 0.01% LAP (lithium phenyl (2,4,6-trimethylbenzoyl)phosphate) to obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained.

[0076] Comparative Example

[0077] This comparative example provides a method for preparing silk fibroin hydrogel, the method comprising the following steps:

[0078] (1) Degumming: Add silk to sodium carbonate solution and heat to obtain degummed silk;

[0079] (2) Modification: The degummed silk is dissolved in lithium bromide solution, and then glycidyl methacrylate is added to react and a reaction solution is obtained;

[0080] (3) Dialysis: Dialyze the reaction solution to obtain the supernatant;

[0081] (4) Freeze-drying: Freeze-dry the supernatant to obtain freeze-dried protein;

[0082] (5) Gel formation: The freeze-dried protein is mixed with a photoinitiator solution and the freeze-dried protein solution is irradiated with blue-violet light to obtain the silk fibroin hydrogel.

[0083] Effect verification

[0084] I. Phenotypes of Photocrosslinked Dual-Network Hydrogels

[0085] The sol prepared in Example 1 was placed in a glass container and then irradiated with ultraviolet light. A sol-gel transition occurred, and the solution lost its fluidity. After inverting the container for 1 minute, there was no flow, indicating successful hydrogel formation. The results are as follows: Figure 1 As shown.

[0086] II. Morphological observation of photocrosslinked double-network hydrogels

[0087] like Figure 2As shown, the photocrosslinked double-network hydrogel prepared in Example 1 and the silk fibroin hydrogel prepared in the comparative example were freeze-dried and then dried in a dryer for 24 hours. The surface morphology and porous structure of the two were observed using a scanning electron microscope. Figure 2 The left image shows the silk fibroin hydrogel prepared in the comparative example, and the right image shows the photocrosslinked double-network hydrogel prepared in Example 1. Figure 2 As can be seen, the hydrogel prepared in the comparative example has a single-layer mesh structure, while the hydrogel prepared by introducing oxidized dextran in this invention has a double-layer network structure with a dense internal mesh structure, making the structure more compact.

[0088] III. Testing of the Self-Healing and Injectability Properties of Photocrosslinked Dual-Network Hydrogels

[0089] (I) Self-healing performance test

[0090] like Figure 3 As shown, two hydrogels of the same shape and size were prepared according to Example 1. Then, the two hydrogels were stained with rhodamine and methylene blue, respectively. The two stained hydrogels were cut in half, and then the two hydrogels of different colors were spliced ​​together. After 5 minutes, it was observed that the two spliced ​​hydrogels successfully healed without obvious gaps, and there was no breakage when stretched. The above results show that the silk fibroin hydrogel prepared by the present invention can effectively achieve self-healing.

[0091] (II) Injectability Testing

[0092] like Figure 4 As shown, the sol prepared in Example 1 was first drawn into a syringe, and the syringe was irradiated with an ultraviolet light source to cause the sol to form a hydrogel. After the hydrogel formed, it was stained with rhodamine. Then, the syringe needle was inserted below the liquid surface, and the hydrogel was observed by taking pictures during injection. Figure 4 It can be observed that it can be easily injected and the injected hydrogel is intact and coherent, without breaking or shattering, indicating that it has injectable properties.

[0093] IV. Hydrogel Rheological Properties Testing

[0094] (1) Rheological tests were performed using an AR 2000ex (TAinstrument) rheometer with a 25 mm stainless steel flat disc fixture and a fixture gap of 400 micrometers.

[0095] (2) The hydrogel prepared in Example 1 was added to the rheometer and the rheological properties of the sample were measured in the time range of 0-500s.

[0096] (3) Test and record the elastic modulus (storage modulus) of the hydrogel (G).’ ) and viscous modulus (loss modulus) (G ” The changes over time, with a frequency of 1 radian / second.

[0097] (4) The results are as follows Figure 5 As shown, from Figure 5 As can be seen from the data, during the time period of 0-100s, when the pressure is 1%, the storage modulus of the hydrogel (G) is... ’ ) greater than loss modulus (G ” This indicates successful hydrogel formation, with a storage modulus of approximately 200 Pa, demonstrating excellent mechanical properties that meet the standard requirements for use as a dressing. Within a 100-200 s timeframe, the hydrogel begins to break down when the pressure is increased to 1200%, at which point the storage modulus (G) reaches its maximum value. ’ ) less than loss modulus (G ” The hydrogel transforms into a sol state, indicating that it possesses strong compressive strength and will not easily break during use. When the pressure is returned to 1% within a 200-300s period, the hydrogel begins to self-heal, and its storage modulus (G) increases. ’ The pressure recovered to around 200 Pa and was greater than the loss modulus (G). ” The hydrogel returns to a gel state. During a period of 300-400 seconds, when the pressure is increased to 1200%, the hydrogel begins to break down, transforming into a sol state. During a period of 400-500 seconds, when the pressure is reduced back to 1%, the hydrogel begins to self-heal, returning to a gel state. The above tests demonstrate that the silk fibroin hydrogel prepared by this invention possesses strong mechanical properties, is not easily broken when applied to skin wounds, and exhibits rapid healing after breakage.

[0098] V. Rheometer storage modulus and loss modulus tests of dextran with different degrees of oxidation substitution and silk fibroin at different mass ratios

[0099] like Figure 6 As shown, the silk fibroin hydrogels prepared in Examples 1-6 were placed in a rheometer for testing. The model of the rheometer and the testing steps were the same as in "IV. Hydrogel Rheological Properties Test". Under the same mass ratio of silk fibroin to dextran, the storage modulus of dextran with a degree of substitution of 20% was higher than that with a degree of substitution of 40%, indicating that the optimal degree of oxidation substitution of dextran was 20%. Under the same degree of oxidation substitution of dextran (all 20%), the hydrogel performance was the best when the mass ratio of silk fibroin to dextran was 3:1, with the storage modulus maintained at around 200 Pa. At the same time, the intersection point of storage modulus and loss modulus was the largest, and the pressure was 1000%, indicating that the optimal mass ratio of silk fibroin to dextran was 3:1.

[0100] VI. Biocompatibility Testing

[0101] The silk fibroin hydrogels prepared in Examples 1-3 were named hydrogel 1, hydrogel 2, and hydrogel 3, respectively. They were used as test samples, and their biocompatibility was evaluated by measuring their hemolytic activity against human erythrocytes.

[0102] like Figure 7 As shown, 200 μL of each of hydrogels 1, 2, and 3 were added to 1.5 mL EP tubes. Then, 800 μL of 8% human erythrocytes were added to each tube. After incubation at 37°C for 1 hour, the tubes were centrifuged (1200 g) and photographed to observe the degree of heme release. The supernatant was then collected from each tube, and the OD490 was measured to quantitatively calculate the hemolysis rate. Figure 7 This is a graph showing the hemolytic effect of each experimental group on human erythrocytes. Figure 7 As can be seen from the present invention, the hydrogel prepared by the present invention does not exhibit hemolytic activity after incubation with red blood cells, does not cause red blood cell rupture, has no obvious hemolytic toxicity, and has good biocompatibility.

[0103] Although the present invention has been described using the above preferred embodiments, it is not intended to limit the scope of protection of the present invention. Any changes and modifications made by those skilled in the art to the above embodiments without departing from the spirit and scope of the present invention shall still fall within the scope of protection of the present invention.

Claims

1. A method for preparing a self-healing, injectable photocrosslinked dual-network hydrogel, characterized in that, Includes the following steps: (1) Preparation of modified silk fibroin Degummed silk fibroin fibers were dissolved in lithium bromide aqueous solution and stirred at 65°C. While stirring, glycidyl methacrylate solution was added dropwise for methacrylation modification. After stirring for 5-8 hours, a mixed solution was obtained. The mixed solution was dialyzed and freeze-dried to obtain sponge-like modified silk fibroin. (2) Preparation of oxidized dextran Add dextran to deionized water, then add sodium periodate solution dropwise to the dextran solution, stir at room temperature in the dark for 3-6 hours, then add ethylene glycol to stop the reaction, and then dialyze and freeze dry to obtain oxidized dextran. (3) Mix the oxidized dextran solution with the modified silk fibroin solution, then add the photoinitiator solution to mix and obtain a sol. After irradiation with ultraviolet light, a photocrosslinked double network hydrogel can be obtained. The mass ratio of the modified silk fibroin to oxidized dextran is 3:1; the degree of oxidation substitution of the oxidized dextran is 20%.

2. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, The mass ratio of the silk fibroin fiber to the glycidyl methacrylate solution is 10:

3.

3. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, The mass ratio of dextran to sodium periodate solution is 2.5:

1.

4. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, In step (1), the concentration of lithium bromide aqueous solution is 8-10 mol / L; the concentration of glycidyl methacrylate solution is 300-400 mmol / L.

5. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, In step (2), the mass concentration of the sodium periodate solution is 20%.

6. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, In step (3), the mass-volume concentration of the modified silk fibroin aqueous solution is 10-20%; the mass-volume concentration of the oxidized dextran aqueous solution is 5-10%.

7. The method for preparing the self-healing, injectable photocrosslinked dual-network hydrogel according to claim 1, characterized in that, In step (3), the mass-volume concentration of the photoinitiator solution is 0.1-0.2%.

8. A self-healing, injectable, photocrosslinked dual-network hydrogel, characterized in that, It is prepared by the preparation method described in any one of claims 1-7.

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