CN117467160A

CN117467160A - Photo-crosslinked self-healing gelatin hydrogel and preparation method thereof

Info

Publication number: CN117467160A
Application number: CN202311429017.4A
Authority: CN
Inventors: 李敏; 范溦; 张宇涵; 张腾飞; 周张颖
Original assignee: Huaibei Normal University
Current assignee: Huaibei Normal University
Priority date: 2023-10-31
Filing date: 2023-10-31
Publication date: 2024-01-30

Abstract

The invention belongs to the technical field of hydrogel materials, and discloses a photo-crosslinked self-healing gelatin hydrogel and a preparation method thereof; the preparation method comprises the following steps: dispersing gelatin in solvent A, adding functional disulfide to perform Michael addition reaction,then adding a precipitator, collecting precipitate, washing, drying, dialyzing, and drying to obtain modified gelatin; dispersing the modified gelatin in the solvent B, adding a photoinitiator, uniformly mixing, and photocrosslinking under ultraviolet light to form the self-healing gelatin hydrogel; the functional disulfide is 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate, and the chemical formula is shown in formula I; according to the invention, disulfide with acrylic ester and methacrylic ester is used as a modifier to modify gelatin, and the photo-crosslinking and self-healing capabilities of the gelatin are simultaneously given on the basis of almost not changing the original performance of the gelatin, so that new possibilities are provided for the fields of tissue repair, 3D printing and the like.

Description

Photo-crosslinked self-healing gelatin hydrogel and preparation method thereof

Technical Field

The invention relates to the technical field of hydrogel materials, in particular to a photo-crosslinked self-healing gelatin hydrogel and a preparation method thereof.

Background

Hydrogels are three-dimensional crosslinked network polymers rich in hydrophilic groups that are of great interest due to their good hydrophilicity, their adjustable physicochemical properties, and their extracellular matrix-mimicking properties. Hydrogels based on naturally derived and synthetic polymers are now widely used in biological tissue engineering to improve cell behavior and activate molecular signaling through physical and chemical modification. Natural polymer-based hydrogels have superior biocompatibility, superior bioactivity, and low immunogenicity compared to synthetic polymers, however their generally poor mechanical properties and uncontrolled degradation behavior have limited their use to some extent. Among them, gelatin is a common natural polymer hydrolyzed from collagen, and is a common structural protein component in extracellular matrix (ECM) of cartilage, bone, tendon and ligament. Gelatin solution has sol-gel conversion property of forming physical cross-linked hydrogel at low temperature, and has wide application in the industrial fields of food, medicine and the like, but the hydrogel prepared by using natural gelatin has the same defects in aspects of thermal stability, mechanical property and degradation property. Since the molecular chain of gelatin is rich in functional groups such as amino groups, hydroxyl groups, carboxyl groups and the like, it has become a trend to improve the performance of gelatin by chemical crosslinking and imparting a certain functionality. In 2000 Van Den Bulcke et al reported that a method for modifying amino groups in gelatin side chains by using methacrylic anhydride was successful in preparing methacrylated gelatin (GelMA), and a hydrogel was prepared by crosslinking the system under light after further adding a photoinitiator by using the presence of methacrylamide groups (Biomacromolecules, 2000,1 (1): 31-38). The gelatin modified by Methacrylic Anhydride (MA) is only aimed at amino acid residues with the molar ratio of less than 5%, so that no obvious influence is exerted on RGD and other functional amino acid sequences, and the modified gelatin still has excellent biocompatibility and degradability.

Self-healing hydrogels are of great interest because of their unique advantages of autonomously repairing damage, maintaining structural and performance integrity, stable function for long-term use, etc., and are an important development direction for biomaterials. At present, self-healing hydrogels based on gelatin are also studied. For example, the hydrogel prepared by mixing oxidized alginate and gelatin has self-healing property due to Schiff base reaction, and can be used in the fields of injectable biological stents and the like. However, the preparation of the gelatin-based self-healing hydrogel in the prior art usually requires blending with an external cross-linking agent, so that the physical and chemical properties, biocompatibility, degradation performance and the like of the hydrogel are changed, and the oxidized alginate is difficult to degrade when being used for biological tissues. Meanwhile, when the self-healing effect is realized by means of Schiff base, the components are crosslinked and cured in a short time after being mixed, so that the operation difficulty of using the hydrogel material for injection or 3D printing is increased. Therefore, the hydrogel material which is convenient for processing and forming, has good self-healing performance and retains the physical, chemical and biological characteristics of gelatin to the maximum extent is developed, and has strong practical significance.

Therefore, the invention provides a photo-crosslinked self-healing gelatin hydrogel and a preparation method thereof.

Disclosure of Invention

In order to solve the defects in the prior art, the invention provides a photo-crosslinked self-healing gelatin hydrogel and a preparation method thereof. The disulfide containing acrylic ester and methacrylic ester is synthesized, disulfide bond and methacrylic ester can be introduced into a gelatin side chain by taking the disulfide as a modifier through one-step reaction, and the photo-induced crosslinking and self-healing capabilities of the disulfide are simultaneously endowed on the basis of almost not changing the original performance of gelatin, so that new possibilities are provided for the fields of tissue repair, 3D printing and the like.

The invention relates to a photo-crosslinked self-healing gelatin hydrogel and a preparation method thereof, which are realized by the following technical scheme:

the first object of the present invention is to provide a method for preparing a photo-crosslinked self-healing gelatin hydrogel, comprising the steps of:

uniformly dispersing gelatin in the solvent A to form gelatin solution; then adding functional disulfide, and carrying out Michael addition reaction between amino on the gelatin and acrylate groups on the functional disulfide to obtain a mixed solution;

adding a precipitator into the mixed solution, collecting precipitate, washing, drying, dialyzing, and drying to obtain modified gelatin;

uniformly dispersing the modified gelatin in a solvent B to form a modified gelatin solution; adding a photoinitiator into the modified gelatin solution, uniformly mixing, and then photocrosslinking under ultraviolet light to form the self-healing gelatin hydrogel;

wherein the functional disulfide is 2- ((2- (acryloyloxy) ethyl) disulfide) ethyl methacrylate, and the chemical formula is shown in formula I:

preferably, the solvent a is water or a PBS buffer with ph=7.2 to 7.6;

and the mass fraction of the gelatin in the gelatin solution is 10% -20%.

Preferably, the mass ratio of the functional disulfide to the gelatin is 5% -30%: 1.

Preferably, the temperature of the Michael addition reaction is 50-60 ℃ and the reaction time is 10-24 h.

Preferably, the precipitating agent is ethanol;

and the volume ratio of the precipitant to the mixed solution is 6-8:1.

Preferably, the solvent B is water or PBS buffer with ph=7.2 to 7.6;

and the mass fraction of the modified gelatin in the modified gelatin solution is 10% -30%.

Preferably, the photoinitiator is 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone;

and the mass ratio of the photoinitiator to the modified gelatin is 0.5% -2% to 1.

Preferably, during the dialysis, the mass fraction of the precipitate in the dialysate is 10-20%;

the molecular retention of the dialysis bag is 14000Da, the dialysis time is 2-4 days, and water is changed for 2-3 times a day.

Preferably, the time of the ultraviolet irradiation is 10-60 s.

The second object of the invention is to provide a self-healing gelatin hydrogel prepared by the preparation method.

Compared with the prior art, the invention has the following beneficial effects:

in the invention, the solubility, low-temperature gel forming performance and biocompatibility of the gelatin before and after modification are almost unchanged, and the original use occasion of the gelatin is not influenced. The self-healing property of the obtained modified gelatin hydrogel material is related to the disulfide bond grafting rate and the concentration of the modified gelatin solution. The higher the grafting rate is, the higher the concentration of the modified gelatin solution is, and the self-healing property and the mechanical property of the polymer are obviously improved.

The invention introduces disulfide bond and methacrylate ester group into gelatin simultaneously through one-step Michael addition reaction. The prepared modified gelatin has the original physical and chemical properties maintained to the greatest extent, and can be rapidly cured and crosslinked by light under the condition of adding a trace amount of photoinitiator due to the existence of methacrylate groups, and the light curing can be completed within 10 seconds at the shortest according to the content of the modified gelatin in the solution. Meanwhile, due to the existence of disulfide bonds, the hydrogel material can heal rapidly after being damaged, and has good application prospects in the fields of tissue engineering, 3D printing and the like.

The invention also provides a gelatin modification method with strong universality. By utilizing the characteristic that amino selectively reacts with acrylate groups, the molecular structure of the modifier is designed, and various different functional groups can be introduced while introducing photo-crosslinking group methacrylate into gelatin, so that the application value of the gelatin is greatly improved.

Drawings

FIG. 1 is a photograph of a mixture of modified gelatin solution and photoinitiator of example 1 prior to photocuring;

FIG. 2 is a photograph of a self-healing gelatin hydrogel prepared in example 1;

FIG. 3 is a photograph of two hydrogels prior to bonding during the self-healing test of the present invention;

FIG. 4 is a photograph of two hydrogel adhesives after self-healing in the self-healing test of the present invention;

FIG. 5 is a photograph of a hydrogel after self-healing prior to stretching treatment in the self-healing test of the present invention;

FIG. 6 is a photograph of a hydrogel after self-healing after stretching treatment at the time of the self-healing test of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below.

The invention provides a photo-crosslinked self-healing gelatin hydrogel, and the preparation method thereof is as follows:

step one, preparing modified gelatin:

uniformly dispersing gelatin in the solvent A to form gelatin solution; then adding functional disulfide, and carrying out Michael addition reaction between amino on the gelatin and acrylate groups on the functional disulfide to obtain a mixed solution; adding a precipitator into the mixed solution, collecting precipitate, washing, drying, dialyzing, and drying to obtain modified gelatin;

step two, photo-crosslinking to form self-healing gelatin hydrogel:

uniformly dispersing the modified gelatin in a solvent B to form a modified gelatin solution; and adding a photoinitiator into the modified gelatin solution, uniformly mixing, and then photo-crosslinking under ultraviolet irradiation to form the self-healing gelatin hydrogel.

It should be noted that the present invention aims to introduce self-healing ability on the premise of not changing the biocompatibility of gelatin as much as possible, and in consideration of disulfide bonds as common chemical bonds in proteins, disulfide bonds are preferably introduced to impart self-healing ability to gelatin. Therefore, the invention takes 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate as a modifier, and can synchronously introduce methacrylate groups besides introducing disulfide bonds through Michael addition with amino groups in a gelatin side chain, thereby endowing gelatin with photocrosslinking capability. The chemical formula is shown as formula I:

it is also noted that the 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate employed in the present invention is prepared by the steps of:

1) Preparation of 2- ((2-hydroxyethyl) dithio) ethyl acrylate:

uniformly dispersing di (2-hydroxyethyl) disulfide and triethylamine in anhydrous dichloromethane to form a mixed solution A; wherein the dosage ratio of the di (2-hydroxyethyl) disulfide to the triethylamine to the dichloromethane is 15-16 g:10-10.5:100 mL;

slowly dropwise adding an acryloyl chloride solution into the mixed solution A under ice water bath, and continuously stirring at room temperature for 24 hours after the dropwise adding is finished to obtain a mixed solution B; wherein the mass ratio of the acryloyl chloride in the acryloyl chloride solution to the di (2-hydroxyethyl) disulfide is 8-8.4:15-16;

washing the mixed solution B by adopting 1M hydrochloric acid, 1M sodium hydroxide solution and saturated saline water in sequence, collecting an organic phase, drying overnight by adopting anhydrous sodium sulfate, filtering to remove solids, concentrating the solution, purifying by adopting a silica gel column, and obtaining 2- ((2-hydroxyethyl) dithio) ethyl acrylate; wherein, during the purification of the silica gel column, the used leaching agent is ethyl acetate and normal hexane, and the volume ratio of the ethyl acetate to the normal hexane is 1:3.

2) Preparation of 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate from 2- ((2-hydroxyethyl) dithio) ethyl acrylate:

uniformly dispersing acrylic acid 2- ((2-hydroxyethyl) dithio) ethyl ester and triethylamine in anhydrous dichloromethane to form a mixed solvent C; wherein the dosage ratio of the acrylic acid 2- ((2-hydroxyethyl) dithio) ethyl ester, the triethylamine and the anhydrous dichloromethane is 4-4.5 g to 2-2.5 g to 50mL;

slowly dropwise adding a methacryloyl chloride solution into the mixed solution C under ice water bath, and continuously stirring at room temperature for 24 hours after the dropwise adding is finished to obtain a mixed solution D; wherein the mass ratio of the methacryloyl chloride to the acrylic acid 2- ((2-hydroxyethyl) disulfide) ethyl ester in the methacryloyl chloride solution is 4.1-4.3:4-4.5;

washing the mixed solution D by adopting 1M hydrochloric acid, 1M sodium hydroxide solution and saturated saline water in sequence, collecting an organic phase, drying overnight by adopting anhydrous sodium sulfate, filtering to remove solid, concentrating the solution, and purifying by adopting a silica gel column to obtain 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate; wherein, during the purification of the silica gel column, the used leaching agent is ethyl acetate and normal hexane, and the volume ratio of the ethyl acetate to the normal hexane is 1:6.

And the synthetic route is shown in a formula II:

in order to enable the functional disulfide to be sufficiently and uniformly modified, in a preferred embodiment of the present invention, gelatin is first placed in solvent A at 45-55℃and stirred at 1000rpm for 30 minutes to uniformly disperse the forming components, and the forming components are dissolved and uniformly dispersed in solvent A to form a gelatin solution.

In order to avoid the deterioration of the gelatin, so that the gelatin can form a gelatin solution with uniform components, in a preferred embodiment of the invention, the solvent A is ultrapure water or PBS buffer solution with pH=7.2-7.6, and the mass fraction of the gelatin in the gelatin solution is 10-20 percent, so that the gelatin is prevented from deterioration under acidic or alkaline conditions, and meanwhile, the aqueous solvent can ensure that the gelatin is fully dissolved to form the gelatin solution with uniform components.

In order to carry out Michael addition reaction between the amino group on the gelatin and the acrylate group on the functional disulfide, the reaction is carried out under the stirring action, and the stirring speed is set to be 800-1200 r/min in order to ensure that the functional disulfide can be well dispersed. The reaction temperature is 50-60 ℃ and the reaction time is 10-24 h.

The invention removes unreacted functional disulfide as much as possible, ethanol is used as a precipitator, and the volume ratio of the precipitator to the mixed solution is 6-8:1.

In order to avoid the deterioration of the modified gelatin, so that the modified gelatin solution with uniform components can be formed, in a preferred embodiment of the invention, the solvent B is ultrapure water or PBS buffer solution with pH=7.2-7.6, and the mass fraction of the modified gelatin in the modified gelatin solution is 10% -30%, so that the modified gelatin is prevented from deterioration under acidic or alkaline conditions, and meanwhile, the aqueous solvent can ensure that the modified gelatin fully forms the modified gelatin solution with uniform components.

The invention aims at reducing the biotoxicity of the system as much as possible, and adopts a photoinitiator 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-acetone authenticated by FDA; and the mass ratio of the photoinitiator to the modified gelatin is 0.5% -2% to 1.

In the invention, during dialysis, the mass fraction of the sediment in the dialysate is 10-20%; the molecular retention of the dialysis bag is 14000Da, the dialysis time is 2-4 days, and water is changed for 2-3 times a day.

The invention aims to ensure the crosslinking degree of the modified gelatin and avoid damage caused by long-term irradiation of ultraviolet light as much as possible, wherein the irradiation time of the ultraviolet light is 10-60 s.

Example 1

The present example provides a photo-crosslinked self-healing gelatin hydrogel, and its preparation method is as follows:

step 1, preparing a functional disulfide:

step 1.1, preparation of intermediate 2- ((2-hydroxyethyl) dithio) ethyl acrylate:

1) 15.4g of di (2-hydroxyethyl) disulfide and 10.1g of triethylamine are weighed and added into a 250mL round bottom flask containing 100mL of anhydrous dichloromethane to be uniformly mixed to form a mixed solution A;

2) Uniformly dispersing 8.2g of acryloyl chloride in 20mL of anhydrous dichloromethane to form an acryloyl chloride solution;

3) Placing the round-bottom flask in an ice-water bath, then under the ice-water bath, slowly dropwise adding the prepared acryloyl chloride solution into the mixed solution A in the round-bottom flask, and continuously stirring at room temperature for 24 hours after the dropwise adding is finished to obtain a mixed solution B;

4) The mixed solution was washed with 1M hydrochloric acid, 1M sodium hydroxide solution and saturated brine in this order. The organic phase was collected and dried over anhydrous sodium sulfate overnight. The solid was removed by filtration, and the solution was concentrated and purified by a silica gel column to give 2- ((2-hydroxyethyl) disulfide) ethyl acrylate, and the 2- ((2-hydroxyethyl) disulfide) ethyl acrylate obtained in this example was 8.8g, yield 46%.

Step 1.2 preparation of 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate

1) 4.16g of 2- ((2-hydroxyethyl) dithio) ethyl acrylate and 2.2g of triethylamine are added into a 250mL round bottom flask containing 50mL of anhydrous dichloromethane and mixed evenly to form a mixed solution C;

2) Uniformly dispersing 4.2g of methacryloyl chloride in 20mL of anhydrous dichloromethane to form a methacryloyl chloride solution;

3) Slowly dropwise adding the prepared methacryloyl chloride solution into the mixed solution C under ice water bath, and continuously stirring at room temperature for 24 hours after the dropwise adding is finished to obtain a mixed solution D;

4) The above mixed solution D was washed with 1M hydrochloric acid, 1M sodium hydroxide solution and saturated brine in this order, and the organic phase was collected, dried over anhydrous sodium sulfate overnight, and the solid was removed by filtration, and the solution was concentrated and purified by a silica gel column to give 2- ((2- (acryloyloxy) ethyl) disulfide) ethyl methacrylate, and the 2- ((2- (acryloyloxy) ethyl) disulfide) ethyl methacrylate obtained in this example was 5.2g, with a yield of 94%.

Wherein, during the purification of the silica gel column, the used leaching agent is ethyl acetate and normal hexane, and the volume ratio of the ethyl acetate to the normal hexane is 1:6.

And the synthetic route is shown in a formula II:

step 2, preparing modified gelatin:

1) 2g of gelatin was dissolved in 20ml of PBS buffer at 50 ℃ at ph=7.4 to form a gelatin solution;

2) Adding 0.2g of 2- ((2-hydroxyethyl) dithio) ethyl acrylate into the prepared gelatin solution, and stirring at the stirring speed of 1000r/min for reaction for 24 hours at 50 ℃ to obtain a mixed solution;

3) The obtained mixed solution is slowly dripped into 150mL of ethanol, the precipitated product is collected, and the obtained product is placed into a vacuum drying oven for dehumidification to obtain a light yellow solid.

4) The pale yellow solid was redissolved in 20mL deionized water at 50 ℃ and filled into dialysis bags (molecular weight cut-off 14000), dialyzed in deionized water for 3 days, changing water 2 times per day. Finally, freeze-drying the dialyzed liquid to obtain the modified gelatin containing disulfide bonds and methacrylate groups, wherein the synthetic route is shown in a formula III:

step 3, photo-crosslinking to form self-healing gelatin hydrogel:

1) Taking 0.2g of the modified gelatin containing disulfide bonds and methacrylate groups, and dissolving the modified gelatin in 1mL of deionized water at 50 ℃ to form a modified gelatin solution;

2) 1mg of photoinitiator 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone is added into the modified gelatin solution, as shown in figure 1, the obtained product is still in a liquid state, the liquid product is irradiated under an ultraviolet lamp for 10 seconds, and then the gel is formed by solidification, so that the self-healing gelatin hydrogel is obtained, and as shown in figure 2, after the glass bottle with the self-healing gelatin hydrogel formed is inverted, the self-healing gelatin hydrogel is still positioned at the bottom of the glass bottle and cannot flow.

Example 2

step 1, preparing a functional disulfide:

Step 1.2 preparation of 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate

And the synthetic route is shown in a formula II:

step 2, preparing modified gelatin:

1) 2g of gelatin was dissolved in 10ml of PBS buffer at 55 ℃ at ph=7.2 to form a gelatin solution;

2) Adding 0.1g of 2- ((2-hydroxyethyl) dithio) ethyl acrylate into the prepared gelatin solution, and stirring at a stirring rate of 800r/min at 55 ℃ for reaction for 18 hours to obtain a mixed solution;

3) The obtained mixed solution is slowly dripped into 130mL of ethanol, the precipitated product is collected, and the obtained product is placed into a vacuum drying oven for dehumidification to obtain a light yellow solid.

4) The pale yellow solid is redissolved in deionized water at 55 ℃ to form a dialysate, the mass fraction of the pale yellow solid in the formed dialysate is 15%, the dialysate is filled into a dialysis bag (the molecular weight cut-off is 14000), and the dialysate is dialyzed in the deionized water for 2 days, and water is changed for 3 times every day. Finally, freeze-drying the dialyzed liquid to obtain the modified gelatin containing disulfide bonds and methacrylate groups, wherein the synthetic route is shown in a formula III:

step 3, photo-crosslinking to form self-healing gelatin hydrogel:

1) Taking 0.2g of the prepared modified gelatin containing disulfide bonds and methacrylate groups, and dissolving the modified gelatin in deionized water at 50 ℃ to form a modified gelatin solution with the mass fraction of 10%;

2) Adding 2mg of photoinitiator 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone into the modified gelatin solution, and placing the gelatin solution still in a liquid state under an ultraviolet lamp for irradiation for 20 seconds to cure to form gel, thus obtaining the self-healing gelatin hydrogel.

Example 3

step 1, preparing a functional disulfide:

Step 1.2 preparation of 2- ((2- (acryloyloxy) ethyl) dithio) ethyl methacrylate

And the synthetic route is shown in a formula II:

step 2, preparing modified gelatin:

1) 2g of gelatin was dissolved in 15ml of buffer solution at 60℃to form a gelatin solution;

2) Adding 0.6g of 2- ((2-hydroxyethyl) dithio) ethyl acrylate into the prepared gelatin solution, and stirring at a stirring rate of 1000r/min at 60 ℃ for reaction for 10 hours to obtain a mixed solution;

3) The obtained mixed solution is slowly dripped into 170mL of ethanol, the precipitated product is collected, and the obtained product is placed into a vacuum drying oven for dehumidification to obtain a light yellow solid.

4) Redissolving the pale yellow solid in deionized water at 60 ℃ to form a dialysate, wherein the mass fraction of the pale yellow solid in the formed dialysate is 20%, placing the dialysate into a dialysis bag (with a molecular weight cut-off of 14000), dialyzing in the deionized water for 4 days, and changing water 2 times a day. Finally, freeze-drying the dialyzed liquid to obtain the modified gelatin containing disulfide bonds and methacrylate groups, wherein the synthetic route is shown in a formula III:

step 3, photo-crosslinking to form self-healing gelatin hydrogel:

1) Taking 0.2g of the modified gelatin containing disulfide bonds and methacrylate groups, and dissolving the modified gelatin in deionized water at 60 ℃ to form a modified gelatin solution with the mass fraction of 30%;

2) Adding 4mg of photoinitiator 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone into the modified gelatin solution, and placing the gelatin solution still in a liquid state under an ultraviolet lamp for irradiation for 30 seconds to cure to form gel, thus obtaining the self-healing gelatin hydrogel.

Experimental part

In the invention, the self-healing property of the modified gelatin is considered to be positively correlated with the gelatin content and the crosslinking degree thereof, so the self-healing test of the modified gelatin hydrogel is carried out by taking the self-healing gelatin hydrogel prepared in the example 1 as an example:

1g of modified gelatin containing disulfide bonds and methacrylate groups is dissolved in 5mL of deionized water at 50 ℃,10 mg of photoinitiator 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone is added, the solution is added into a bar-shaped mold, and the bar-shaped mold is placed under an ultraviolet lamp for irradiation for 10 seconds to gel, and the irradiation time is prolonged to 1 minute to increase the crosslinking degree. The rod-shaped modified gelatin hydrogel is taken out, and is put into a baking oven at 50 ℃ for heating for 2 hours to enable the water loss to reach about 2g, and the modified gelatin hydrogel with the water content of about 100% is obtained.

The shaped bar-shaped hydrogel was cut into two halves from the middle, and half was put into rhodamine solution for staining, and the other half was not stained, as shown in fig. 3, and in fig. 3, the bar-shaped hydrogel was stained on the left side, and the bar-shaped hydrogel was not stained on the right side. Two hydrogels as shown in fig. 3 were adhered along the incision, and after 10 minutes, a material as shown in fig. 4 was obtained, and the blurring at the incision was observed from fig. 4. Subsequently, as shown in fig. 5, both sides are gripped by two tweezers, and stretched, respectively, to both sides, and the stretched material is shown in fig. 6. And the test result shows that the rod-shaped hydrogel can not break when being stretched to about twice the original length, thus indicating that the hydrogel successfully realizes self-healing.

It should be apparent that the embodiments described above are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.

Claims

1. A method for preparing photo-crosslinked self-healing gelatin hydrogel, which is characterized by comprising the following steps:

uniformly dispersing gelatin in the solvent A to form gelatin solution; then adding functional disulfide, and carrying out Michael addition reaction between amino on the gelatin and acrylate groups on the functional disulfide to obtain a mixed solution; adding a precipitator into the mixed solution, collecting precipitate, washing and drying, and dialyzing and drying the dried product to obtain modified gelatin;

2. the method of claim 1, wherein solvent a is water or PBS buffer at ph=7.2-7.6;

and the mass fraction of the gelatin in the gelatin solution is 10% -20%.

3. The method of claim 1, wherein the mass ratio of the functional disulfide to the gelatin is 5% to 30% to 1.

4. The process according to claim 1, wherein the temperature of the Michael addition reaction is 50 to 60℃and the reaction time is 10 to 24 hours.

5. The method of claim 1, wherein the precipitating agent is ethanol;

and the dosage ratio of the precipitant to the gelatin is 130-170 mL/2 g.

6. The method of claim 1, wherein solvent B is water or PBS buffer at ph=7.2-7.6;

7. The method of claim 1, wherein the photoinitiator is 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone;

8. The method according to claim 1, wherein the mass fraction of the dry product in the dialysate during the dialysis is 10% to 20%;

9. The method according to claim 1, wherein the time of the ultraviolet irradiation is 10 to 60 seconds.

10. A self-healing gelatin hydrogel prepared by the method of any one of claims 1-9.