CN110935057A

CN110935057A - Application of dopamine-based tissue adhesive in antibacterial biomedical materials

Info

Publication number: CN110935057A
Application number: CN201811110483.5A
Authority: CN
Inventors: 王玮; 谢田
Original assignee: Tianjin University
Current assignee: Tianjin University
Priority date: 2018-09-21
Filing date: 2018-09-21
Publication date: 2020-03-31

Abstract

The invention provides application of a dopamine-based tissue adhesive in antibacterial biomedical materials, which is characterized in that a gelatin aqueous solution is added into a hyperbranched polyaminoester polymer (HB-PBAE) solution, after the mixture is subjected to vortex centrifugal mixing uniformly, a ferric chloride hexahydrate solution is added into the solution, the mixture is subjected to vortex centrifugal mixing uniformly again, a polyvinyl imidazole (PVI) solution is added into the mixed solution again, after the mixture is subjected to vortex centrifugal mixing uniformly, a metal ion responsive gel is obtained, and the gel is soaked in a transition metal ion solution, so that the dopamine-based tissue adhesive with an antibacterial effect is obtained. The activity of bacteria in a culture medium in which the metal ion responsive gel soaked with copper ions, nickel ions and zinc ions is located is low, and the metal ion responsive gel is proved to have a good sterilization effect.

Description

Application of dopamine-based tissue adhesive in antibacterial biomedical materials

Technical Field

The invention relates to the technical field of high polymer materials, in particular to application of a dopamine-based tissue adhesive in an antibacterial biomedical material.

Background

The hydrogel is a three-dimensional network structure, has a good moisturizing effect on wounds due to high water content, can effectively promote the healing of the wounds, has good biocompatibility and self-repairing performance, and provides a wide application space for the gel in the aspects of biomedical sensors, self-repairing materials and wound dressings due to the excellent performance.

Stimuli-responsive hydrogels are a class of biomaterials that respond to external environmental stimuli with a corresponding physical, chemical, or conformational change. The traditional stimulation responsive hydrogel mainly comprises pH responsive gel, temperature sensitive gel, photosensitive gel, ion responsive gel, electromagnetic responsive gel and the like. In response, some of the basic material properties of the gel, such as swelling, porosity, physical structure, and modulus, change. Stimuli-responsive gels have been extensively studied in recent years and have found good applications in drug delivery, biosensors and tissue engineering scaffolds.

The complexation and decomplexing effects of imidazole groups and transition metal ions are widely studied, and most of divalent metal ions can be well complexed with imidazole groups and play an important role in organisms. Wherein, the metal ions can also be complexed with imidazole groups, and the good antibacterial effect of the metal ions provides guarantee for the metal ions to be used as skin wound dressings.

Disclosure of Invention

The invention overcomes the defects in the prior art and provides the application of a dopamine-based tissue adhesive in antibacterial biomedical materials²⁺、Zn²⁺、Ni²⁺Complexing, namely enabling the gel to have good metal ion responsiveness, soaking the gel in a solution of transition metal ions to complex imidazole groups in the gel with the transition metal ions, and further enabling the gel to have antibacterial property.

The purpose of the invention is realized by the following technical scheme.

The application of the dopamine-based tissue adhesive in the antibacterial biomedical materials is carried out according to the following steps:

step 1, dissolving a 1-Vinyl Imidazole (VI) monomer, a chain transfer agent tetraethyl thiuram Disulfide (DS) and an initiator Azobisisobutyronitrile (AIBN) in N-N Dimethylformamide (DMF), uniformly mixing, vacuumizing, reacting in an oil bath at 60-80 ℃ for 5-9h, and purifying with cold ether to obtain polyvinyl imidazole (PVI);

step 2, putting gelatin in a water bath at 36-38 ℃ to fully dissolve to obtain a gelatin aqueous solution, adding the gelatin aqueous solution into a hyperbranched polyaminoester polymer (HB-PBAE) solution, performing vortex centrifugation and uniform mixing, then adding a ferric chloride hexahydrate solution into the solution, performing vortex centrifugation and uniform mixing again, adding a Polyvinylimidazole (PVI) solution into the mixed solution again, performing vortex centrifugation and uniform mixing to obtain a metal ion responsive gel;

wherein the molar ratio of the 1-Vinyl Imidazole (VI) monomer, the chain transfer agent tetraethyl thiuram Disulfide (DS) and the initiator Azobisisobutyronitrile (AIBN) is (40-60): (1-3), (1-3) the final concentration of iron ions (the final concentration being the sum of the volumes of an iron ion/gelatin aqueous solution, a hyperbranched polyaminoester polymer (HB-PBAE) solution, a ferric chloride hexahydrate solution and a Polyvinylimidazole (PVI) solution) is 80-120mM, and the ratio of the final mass fractions of gelatin, hyperbranched polyaminoester polymer (HB-PBAE) and Polyvinylimidazole (PVI) (the final mass fraction being the sum of the volumes of gelatin or hyperbranched polyaminoester polymer (HB-PBAE) or Polyvinylimidazole (PVI)/gelatin aqueous solution, hyperbranched polyaminoester polymer (HB-PBAE) solution, a ferric chloride hexahydrate solution and a Polyvinylimidazole (PVI) solution) is (3-15%): (5-30%): (5-15%).

In step 1, the molar ratio of 1-Vinylimidazole (VI) monomer, chain transfer agent tetraethylthiuram Disulfide (DS), and initiator Azobisisobutyronitrile (AIBN) is (45-55): (1-2):(2-3).

In the step 1, the reaction temperature is 65-75 ℃, and the reaction time is 6-7 h.

In step 2, the final concentration of iron ions is 90-110 mM.

In step 2, the final mass fraction ratio of gelatin, hyperbranched polyaminoester polymer (HB-PBAE) and Polyvinylimidazole (PVI) is (5-10%): (10-20%): (8-12%).

The invention has the beneficial effects that: the invention uses RAFT method to synthesize polyvinyl imidazole (PVI)Is one of the raw materials of the gel, wherein a plurality of imidazole groups contained in the gel can react with transition metal ions Cu²⁺、Zn²⁺、Ni²⁺The gel has good metal ion responsiveness by complexing, the rheological property of the gel can be obviously tested to obviously observe that the storage modulus of the gel after responding to the metal ions is obviously increased, in addition, the lap shear adhesion property of the gel is tested to find that the maximum adhesion strength of the gel after being soaked in the zinc ion solution for a short time is reduced to 20 percent before being soaked, and the gel is proved to be metal ion responsiveness gel by the mutation of the storage modulus and the sudden reduction of the adhesion force; the activity of bacteria in a culture medium in which the metal ion responsive gel soaked with copper ions, nickel ions and zinc ions is located is low, and the metal ion responsive gel is proved to have a good sterilization effect.

Drawings

FIG. 1 is a scanning electron microscope image of a metal ion responsive gel prepared according to the present invention;

FIG. 2 is a comparison graph of the lap shear adhesion performance of the metal ion responsive gel prepared by the present invention before and after the lap shear adhesion performance test;

FIG. 3 is a graph of shear strength versus displacement of a zinc ion solution soaked in a metal ion responsive gel prepared in accordance with the present invention over various periods of time;

FIG. 4 is a curve showing the change of storage modulus of gels with time when different metal ions are respectively added dropwise at the 300 th time after the metal ion responsive gel prepared by the invention is subjected to in-situ gelling;

FIG. 5 is a process of constructing a wound model of rat back and pictures after drug administration;

FIG. 6 is a photograph of in situ gelation of a metal ion responsive gel prepared in accordance with the present invention on a rat back trauma model;

FIG. 7 is a graph showing wound healing at different time periods in a rat back wound model after a metal ion responsive gel prepared according to the present invention, wherein ① is a blank group, ② is a metal ion responsive gel treatment after skin wound, and Zn is not sprayed at dressing change²⁺Solution ③ is prepared by treating skin wound with metal ion responsive gel, and spraying Zn before dressing change²⁺The solution is prepared by mixing a solvent and a solvent,④ spraying Zn only on skin wound²⁺Solution, ⑤ is a commercial debridement gel after skin trauma;

FIG. 8 is a bacteriostatic test chart of cultured Escherichia coli and Staphylococcus aureus respectively obtained by the preparation method of the present invention, wherein a is cultured Escherichia coli, b is cultured Staphylococcus aureus, c is a statistical analysis chart of the diameter of the bacteriostatic ring observed in the culture medium with cultured Escherichia coli, d is a statistical analysis chart of the diameter of the bacteriostatic ring observed in the culture medium with cultured Staphylococcus aureus, 1 is a metal ion responsive gel, 2 is a metal ion responsive gel soaked with calcium ions, 3 is a metal ion responsive gel soaked with copper ions, 4 is a metal ion responsive gel soaked with nickel ions, and 5 is a metal ion responsive gel soaked with zinc ions;

FIG. 9 is a graph showing the statistical analysis of the relative activities of Staphylococcus aureus and Escherichia coli in a medium containing a metal ion-responsive gel soaked with different kinds of metal ions, as measured by the bacterial suspension method, wherein a is the culture of Escherichia coli, b is the culture of Staphylococcus aureus, 1 is the metal ion-responsive gel, 2 is the metal ion-responsive gel soaked with calcium ions, 3 is the metal ion-responsive gel soaked with copper ions, 4 is the metal ion-responsive gel soaked with nickel ions, and 5 is the metal ion-responsive gel soaked with zinc ions.

Detailed Description

The technical solution of the present invention is further illustrated by the following specific examples.

Example 1

5.8825g of 1-Vinylimidazole (VI) are taken in a 10ml centrifuge tube, 0.37g of tetraethylthiuram Disulfide (DS) is taken in a 4ml centrifuge tube, 0.41g of Azobisisobutyronitrile (AIBN) is taken in a 4ml centrifuge tube, 25ml of N-N Dimethylformamide (DMF) is taken in a 50ml beaker, finally the weighed materials are placed in a 100ml round bottom flask for full mixing, then the flask is vacuumized under the stirring of a rotor to remove oxygen therein and then filled with nitrogen, the operation process is repeatedly circulated for 3 times, after the flask is in a nitrogen environment, the reaction device is placed in an oil bath at 70 ℃ for heating for 6 h. And naturally cooling the device to room temperature of 20-25 ℃ after the reaction is finished, then purifying by using cold ether, wherein the amount of the ether is about 5 times of that of the product during purification, the total purification time is 3 times, and the amount of the purifying agent is 4 times of that of the reactant when the purification is carried out to the last time, so that the polyvinyl imidazole (PVI) is obtained.

Putting gelatin in a water bath at 37 ℃ to fully dissolve to obtain a gelatin aqueous solution, wherein the mass fractions of the gelatin aqueous solution, polyvinyl imidazole (PVI) and hyperbranched polyaminoester polymer (HB-PBAE) solution are 5%, 10% and 10% respectively; preparing 900mM iron ion solution; weighing 100 mu l of gelatin solution, placing the gelatin solution into a 4ml centrifuge tube filled with 34 mu l of hyperbranched polyaminoester polymer (HB-PBAE) solution, carrying out vortex mixing, then continuously adding 27 mu l of ferric chloride hexahydrate solution, carrying out vortex mixing again, and finally adding 50 mu l of polyvinyl imidazole (PVI) solution to obtain the metal ion responsive gel.

As shown in FIG. 1, the metal ion responsive gel presents a porous entangled structure in morphology due to the presence of the hyperbranched aminoester polymer (HB-PBAE).

Testing the performance of the metal ion responsive gel:

uniformly smearing the metal ion responsive gel on a glass slide, covering another glass slide, clamping the glass slide by a clamp, and preparing to measure the lap joint shear adhesion strength after 10 min; as shown in figure 2, a 10kgf sensor is selected during stretching, the stretching speed is set to be 2mm/min, a square black area is an area where the gel tightly adheres the two glass slides before stretching, and after stretching, the area has a wire drawing phenomenon, which proves that the gel has good adhesion to the glass slides before the metal ion responsiveness occurs.

As shown in FIG. 3, it can be seen that the maximum shear strength of the gel after soaking the zinc ion solution for 10min is reduced from 29.9kPa to 6.2kPa, the adhesion capacity is only 20% of the initial value, it can be seen that the complexing efficiency of the zinc ions and the imidazole groups is very high, the maximum shear strength of the gel is further reduced with the soaking time, the viscosity is further reduced, and the adhesion strength is only 4.1kPa after half an hour.

Setting the test time of a rheometer as 600s, the frequency as 1Hz and the test temperature as 20-25 ℃ at room temperature; after the metal ion responsive gel is subjected to in-situ gelling on a rheometer, starting to test a time scanning spectrogram, after the time scanning spectrogram is tested for 300s, dropwise adding 200mM zinc sulfate aqueous solution around the metal ion responsive gel, and then continuing to test; as shown in FIG. 4, except for calcium ions, the gels dropwise added with zinc ions, copper ions and nickel ions have magnitude-order mutation of storage modulus at 300s, wherein the gel response change of the dropwise added nickel ions is most obvious, the storage modulus change is 11000-11500kPa, the metal ion responsiveness of the gels dropwise added with copper ions is weaker, and the storage modulus change is 2200-2500kPa, so that the nickel ions, the zinc ions and the copper ions can be complexed with imidazole groups, and the metal ion responsiveness is good. And the change of storage modulus in the order of magnitude of the gel proves that the rebound effect of the gel is weakened and the hardness is increased.

Example 2

Design a blank group of ①, 4 experimental groups, wherein ② is that after skin trauma, the gel is treated by metal ion responsive gel, and Zn is not sprayed during dressing change²⁺Solution ③ is prepared by treating skin wound with metal ion responsive gel, and spraying Zn before dressing change²⁺Solution, ④ spray application of Zn alone to skin wounds²⁺Solution, ⑤, was treated with a commercially available debridement gel after skin trauma.

Firstly, injecting a proper amount of chloral hydrate into a rat to anaesthetize the rat, then fixing the limbs of the rat on an operation board by rubber bands respectively, and then removing rat hair on the back of the rat by using an animal electric hair clipper and disinfecting the rat hair by using iodophor; secondly, covering a circular ring pattern with the diameter of about 1.5cm on the back of the rat by Indonesia, cutting off the skin of the rat by a sterilized scalpel according to the circular ring pattern on the back of the rat, and taking care to separate the rat from muscle tissues so as to avoid accidentally injuring the muscle tissues; finally, a silicone ring cut in the laboratory and having an inner diameter of 1.6cm and an outer diameter of 2.4cm was sutured around the wound with surgical sutures.

Preparing gel with the total mass of 600mg, wherein the mass fractions of the hyperbranched polyaminoester polymer (HB-PBAE) solution, the Polyvinylimidazole (PVI) and the gelatin aqueous solution are respectively 10%, 10% and 5%, and the final concentration of iron ions is controlled at 100 mM.

Transferring the prepared gel precursor solution into an injector, slowly injecting the prepared gel precursor solution onto skin wounds of ②③ two control groups, sticking a sterile transparent dressing after the gel is completely formed in situ, and coating gauze and a self-adhesive bandage, ④ group and ⑤ group are respectively coated with a zinc ion solution and a commercially available debridement gel, and the transparent dressing and the bandage are stuck after the application of the gel is finished.

The rats were changed every three days, ③ group was changed after spraying zinc sulfate solution on the residual drug, the other experimental groups were changed directly, the control group was not treated at all, and the healing of the rat wounds was recorded by taking pictures at each change.

As shown in fig. 6, the metal ion responsive gel was successfully extruded from the syringe and gelled in situ on the wound.

As shown in fig. 7, the overall wound healing was observed to find that the wounds of each group were substantially healed on day 15, wherein the metal ion responsive gel that had been changed after the metal ion response had the best healing effect with the commercially available gel group, and further, comparing ②③ at the time of change on day four, it was found that the wound that had not been sprayed with zinc ions before the change had serious secondary damage to the wound that had not been healed due to the adhesion of the gel to the wound during the change, and the healing rate of the skin wound on the back of the rat was severely slowed down, but in group ③, since zinc sulfate solution was sprayed before the change, the gel had metal ion response, causing it to become hard and weak adhesion, so that the metal ion responsive gel could be easily detached from the new tissue without causing damage thereto.

Example 3

And (3) respectively distributing 450 mu L of water into 4ml centrifuge tubes filled with 60mg of hyperbranched polyaminoester polymer (HB-PBAE), 60mg of polyvinyl imidazole (PVI), 30mg of gelatin and 0.0091g of ferric chloride hexahydrate, fully and uniformly mixing by vortex, transferring into a parallel plate clamp with the diameter of 15mm and the thickness of 1mm, and taking out after the gel is completely formed.

Sterilizing the disc-shaped gel in 75% ethanol solution, replacing once every 30min for 5 times, and replacing ethanol with sterile pure water at the same time interval and frequency as the ethanol solution.

Weighing 1g of tryptone, 0.5g of yeast and 1g of sodium chloride, pouring the tryptone, the yeast and the sodium chloride into 100mL of water, fully stirring for 30-50min, transferring the mixed solution into a conical flask after the solution is clarified, sealing the conical flask with newspaper, putting the conical flask into a sterilization pot for sterilization for 1h, and finally cooling the culture medium to room temperature in a super clean bench.

The preparation of the solid culture medium only needs to add agarose with the mass fraction of 1.5% into the liquid culture medium.

The frozen bacteria are put into a water bath constant temperature oscillator at 42 ℃ and are rapidly oscillated for about 40s at the oscillation speed of 220rmp, and the bacteria can be recovered.

Putting the recovered bacteria into solid and liquid culture media filled with gel discs and chopped gel respectively in a super clean bench, and culturing for 12h in an incubator.

Observing the diameter of the gel inhibition ring around the solid medium

Taking five 10mL sterilized centrifuge tubes, adding 5mL sterilized liquid culture medium and 50 μ L bacteria suspension, using one as blank group, adding 200mg of sterile minced gel soaked with zinc ions, nickel ions, copper ions and calcium ions into the other four sterilized centrifuge tubes respectively, vibrating at 37 ℃ for 6h at the rotation speed of 220rpm, closing the constant temperature oscillator, standing, taking supernatant, measuring absorbance of the supernatant at the wavelength of 600nm, and calculating the relative activity of bacteria. Wherein the calculation formula is as follows: relative activity-Abs samples/Abs blanks, where blank is bacteria-loaded medium without any added gel.

As shown in FIG. 8, the diameter of the metal ion responsive gel bacteriostatic ring soaked with copper ions, nickel ions and zinc ions in the culture medium cultured with Staphylococcus aureus is 7-9mm, the diameter of the metal ion responsive gel bacteriostatic ring soaked with copper ions, nickel ions and zinc ions in the culture medium cultured with Escherichia coli is 6-8mm, all three ions show good antibacterial effect, and no bacteriostatic ring appears around the metal ion responsive gel soaked with metal ions and calcium ions in the culture medium of two different strains; the statistical result is consistent with a and b, and the gel soaked with the copper ions, the nickel ions and the zinc ions generates obvious bacteriostatic rings in the culture media of the two strains, so that the good antibacterial effect is proved.

As shown in fig. 9, the metal ion responsive gel soaked with copper ions, nickel ions and zinc ions has low bacterial activity in the culture medium, which proves that the metal ion responsive gel has good sterilization effect.

Example 4

11.765g of 1-Vinylimidazole (VI) are taken in a 50ml beaker, 0.74g of tetraethylthiuram Disulphide (DS) is taken in a 4ml centrifuge tube, 0.82g of Azobisisobutyronitrile (AIBN) is taken in a 4ml centrifuge tube, 50ml of N-N Dimethylformamide (DMF) is taken in a 100ml beaker, finally the weighed materials are placed in a 100ml round bottom flask for full mixing, then the flask is vacuumized under the stirring of a rotor to remove oxygen therein and then filled with nitrogen, the operation process is repeatedly circulated for 3 times, the flask is placed in a nitrogen environment, and then the reaction device is placed in an oil bath at 60 ℃ for heating for 9 hours. And naturally cooling the device to room temperature of 20-25 ℃ after the reaction is finished, then purifying by using cold ether, wherein the amount of the ether is about 5 times of that of the product during purification, the total purification time is 3 times, and the amount of the purifying agent is 4 times of that of the reactant when the purification is carried out to the last time, so that the polyvinyl imidazole (PVI) is obtained.

Putting gelatin in a water bath at 36 ℃ to fully dissolve to obtain a gelatin aqueous solution, wherein the mass fractions of the gelatin aqueous solution, polyvinyl imidazole (PVI) and hyperbranched polyaminoester polymer (HB-PBAE) solution are 5%, 10% and 5% respectively; preparing 900mM iron ion solution; weighing 100 mu l of gelatin solution, placing the gelatin solution into a 4ml centrifuge tube filled with 17 mu l of hyperbranched polyaminoester polymer (HB-PBAE) solution, carrying out vortex mixing, then continuously adding 27 mu l of ferric chloride hexahydrate solution, carrying out vortex mixing again, and finally adding 50 mu l of Polyvinylimidazole (PVI) solution to obtain the metal ion responsive gel.

Example 5

11.765g of 1-Vinylimidazole (VI) are taken in a 50ml beaker, 0.74g of tetraethylthiuram Disulphide (DS) is taken in a 4ml centrifuge tube, 0.82g of Azobisisobutyronitrile (AIBN) is taken in a 4ml centrifuge tube, 50ml of N-N Dimethylformamide (DMF) is taken in a 100ml beaker, finally the weighed materials are placed in a 100ml round bottom flask for full mixing, then the flask is vacuumized under the stirring of a rotor to remove oxygen therein and then filled with nitrogen, the operation process is repeatedly circulated for 3 times, the flask is placed in a nitrogen environment, and then the reaction device is placed in an oil bath at 80 ℃ for heating for 5 hours. And naturally cooling the device to room temperature of 20-25 ℃ after the reaction is finished, then purifying by using cold ether, wherein the amount of the ether is about 5 times of that of the product during purification, the total purification time is 3 times, and the amount of the purifying agent is 4 times of that of the reactant when the purification is carried out to the last time, so that the polyvinyl imidazole (PVI) is obtained.

Putting gelatin in a water bath at 38 ℃ to fully dissolve to obtain a gelatin aqueous solution, wherein the mass fractions of the gelatin aqueous solution, polyvinyl imidazole (PVI) and hyperbranched polyaminoester polymer (HB-PBAE) solution are 5%, 10% and 20% respectively; preparing 900mM iron ion solution; weighing 100 mu l of gelatin solution, placing the gelatin solution into a 4ml centrifuge tube filled with 68 mu l of hyperbranched polyaminoester polymer (HB-PBAE) solution, carrying out vortex mixing, then continuously adding 27 mu l of ferric chloride hexahydrate solution, carrying out vortex mixing again, and finally adding 50 mu l of Polyvinylimidazole (PVI) solution to obtain the metal ion responsive gel.

Example 6

2.9413g of 1-Vinylimidazole (VI) is taken in a 5ml centrifuge tube, 0.185g of tetraethylthiuram Disulfide (DS) is taken in a 4ml centrifuge tube, 0.205g of Azobisisobutyronitrile (AIBN) is taken in a 4ml centrifuge tube, 12.5ml of N-N Dimethylformamide (DMF) is taken in a 50ml beaker, finally the weighed materials are placed in a 50ml round bottom flask for full mixing, then the flask is vacuumized under the stirring of a rotor to remove oxygen therein and then filled with nitrogen, the operation process is repeatedly circulated for 3 times, the flask is in a nitrogen environment, and then the reaction device is placed in an oil bath at 65 ℃ for heating for 7 h. And naturally cooling the device to room temperature of 20-25 ℃ after the reaction is finished, then purifying by using cold ether, wherein the amount of the ether is about 5 times of that of the product during purification, the total purification time is 3 times, and the amount of the purifying agent is 4 times of that of the reactant when the purification is carried out to the last time, so that the polyvinyl imidazole (PVI) is obtained. Putting gelatin in a water bath at 37 ℃ to fully dissolve to obtain a gelatin aqueous solution, wherein the mass fractions of the gelatin aqueous solution, polyvinyl imidazole (PVI) and hyperbranched polyaminoester polymer (HB-PBAE) solution are 5%, 10% and 30% respectively; preparing 900mM iron ion solution; weighing 100 mu l of gelatin solution, placing the gelatin solution into a 4ml centrifuge tube filled with 102 mu l of hyperbranched polyaminoester polymer (HB-PBAE) solution, carrying out vortex mixing, then continuously adding 27 mu l of ferric chloride hexahydrate solution, carrying out vortex mixing again, and finally adding 50 mu l of Polyvinylimidazole (PVI) solution to obtain the metal ion responsive gel.

The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.

Claims

1. The application of the dopamine-based tissue adhesive in antibacterial biomedical materials is characterized in that: putting gelatin in a water bath at 36-38 ℃ to fully dissolve to obtain gelatin aqueous solution, adding the gelatin aqueous solution into hyperbranched polyaminoester polymer (HB-PBAE) solution, performing vortex centrifugation and uniform mixing, then adding ferric chloride hexahydrate solution into the solution, performing vortex centrifugation and uniform mixing again, adding polyvinyl imidazole (PVI) solution into the mixed solution again, performing vortex centrifugation and uniform mixing to obtain metal ion responsive gel, and soaking the gel in transition metal ion solution to obtain the dopamine-based tissue adhesive with antibacterial effect;

wherein the final concentration of iron ions is 80-120mM, and the final mass fraction ratio of gelatin, hyperbranched polyaminoester polymer (HB-PBAE) and polyvinyl imidazole (PVI) is (3-15%): (5-30%): (5-15%).

2. Use of a dopamine-based tissue adhesive according to claim 1 in antibacterial biomedical materials, characterized in that: preparation of polyvinyl imidazole (PVI): dissolving 1-Vinylimidazole (VI) monomer, chain transfer agent tetraethyl thiuram Disulfide (DS) and initiator Azobisisobutyronitrile (AIBN) in N-N Dimethylformamide (DMF), uniformly mixing, vacuumizing, placing in an oil bath at 60-80 ℃ for reaction for 5-9h, and purifying cold ethyl ether to obtain the Polyvinylimidazole (PVI), wherein the molar ratio of the 1-Vinylimidazole (VI) monomer to the chain transfer agent tetraethyl thiuram Disulfide (DS) to the initiator Azobisisobutyronitrile (AIBN) is (40-60): (1-3):(1-3).

3. Use of a dopamine-based tissue adhesive according to claim 2 in antibacterial biomedical materials, characterized in that: the molar ratio of 1-Vinylimidazole (VI) monomer, chain transfer agent tetraethylthiuram Disulfide (DS), and initiator Azobisisobutyronitrile (AIBN) is (45-55): (1-2):(2-3).

4. Use of a dopamine-based tissue adhesive according to claim 2 in antibacterial biomedical materials, characterized in that: the reaction temperature is 65-75 ℃, and the reaction time is 6-7 h.

5. Use of a dopamine-based tissue adhesive according to claim 2 in antibacterial biomedical materials, characterized in that: the final mass fraction ratio of gelatin, hyperbranched polyaminoester polymer (HB-PBAE) and polyvinyl imidazole (PVI) is (5-10%): (10-20%): (8-12%).

6. Use of a dopamine-based tissue adhesive according to claim 2 in antibacterial biomedical materials, characterized in that: the final concentration of iron ions is 90-110 mM.

7. Use of a dopamine-based tissue adhesive according to claim 2 in antibacterial biomedical materials, characterized in that: the transition metal ions in the transition metal ion solution are copper ions, nickel ions and zinc ions.

8. Use of a dopamine-based tissue adhesive according to claim 7 in antibacterial biomedical materials, characterized in that: the metal ion responsive gel soaked by copper ions, nickel ions and zinc ions has low bacterial activity in a culture medium, and the metal ion responsive gel is proved to have a sterilization effect.

9. Use of a dopamine-based tissue adhesive according to claim 8 in antibacterial biomedical materials, characterized in that: the diameter of the metal ion responsive gel bacteriostatic ring soaked with copper ions, nickel ions and zinc ions in a culture medium for culturing staphylococcus aureus is 7-9 mm.

10. Use of a dopamine-based tissue adhesive according to claim 8 in antibacterial biomedical materials, characterized in that: the diameter of the metal ion responsive gel bacteriostatic ring soaked with copper ions, nickel ions and zinc ions in a culture medium for culturing escherichia coli is 6-8 mm.