CN112029037A - High-strength degradable antibacterial hydrogel and preparation method thereof - Google Patents
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Abstract
The invention relates to the field of hydrogel, and discloses high-strength degradable antibacterial hydrogel and a preparation method thereof aiming at the technical development trend and the demand of the hydrogel on high strength, degradability and antibacterial performance, the antibacterial hydrogel is prepared from chitosan, multi-valence negative ions, zwitterionic polymer and protein, the zwitterionic polymer and the protein are crosslinked in situ through the action of chemical bonds to form a second crosslinking network, the chitosan and the multi-valence negative ions form a first crosslinking network through coordination, the antibacterial hydrogel has a double-network structure formed by mutually penetrating the first network and the second network, has better mechanical strength and anti-cell adhesion performance and good antibacterial performance, the tensile strength can reach 1.25MPa or even higher, and the degradable performance can be realized while the mechanical strength is met.
Description
Technical Field
The invention relates to the field of hydrogel, in particular to high-strength degradable antibacterial hydrogel and a preparation method thereof.
Background
The hydrogel is a high molecular porous material consisting of a three-dimensional network and a large amount of water, and is widely applied to the fields of tissue engineering, drug delivery, biosensors and the like. The traditional hydrogel has mechanical propertiesLow, poor toughness and limited recoverability, which can not meet the requirement of practical application and limit the application range. In recent years, the double-network technology is considered as one of effective methods for improving the mechanical strength and toughness of hydrogel materials, and has attracted much attention. For example, Rong Jianhua et al (Gan S, Lin W, Zou Y, et al, Nano-hydraulic enhanced double network hydrocarbons with excellent performance for functional application in a molecular reppair [ J]Carbohydrate Polymers,2020,229,115523.) developed a double physically cross-linked poly (vinyl alcohol) -nano hydroxyapatite/quaternized chitosan hydrogel with excellent tensile strength (2.70 ± 0.24MPa), toughness (14.09 ± 2.06 MJ/m)3) Wear resistance and excellent cell compatibility, and can be used for cartilage repair.
Compared with non-degradable hydrogel, the biodegradable hydrogel can be degraded into safe and non-toxic micromolecules, the harm to human bodies is minimum, and the material of the type better meets the requirements of medical materials. The degradability of hydrogels is becoming more and more important. Wang Yanqin et al (Wang Y, Xue Y, Wang J, et al. A Composite Hydrogel with High Mechanical Strength, Fluorence, and Degradable Behavior for Bone Tissue Engineering [ J ] Polymers, 2019,11,1112.) prepared a Composite Hydrogel of carbon dots/hydroxyapatite/poly (vinyl alcohol) with co-reinforced nanofiller and double-network structure, which had High Mechanical Strength and outstanding Behavior degradability, and was used in the field of Bone Tissue Engineering.
In addition, bacterial infection is acute systemic infection caused by the invasion of pathogenic bacteria or conditional pathogenic bacteria into blood circulation to grow and reproduce and generate toxins and other metabolites, is clinically characterized by chills, hyperpyrexia, rash, arthralgia and hepatosplenomegaly, and can partially cause symptoms such as infectious shock and the like. Infectious diseases are still the second leading cause of death worldwide. The antibacterial and anti-adhesive properties of hydrogels for biomedical applications are essential to avoid bacterial infections and to promote wound healing. Guo Bailin et al (ZHao X, Liang Y, Huang Y, et al. physical Double-Network Hydrogel Adhesives with Rapid Shape Adaptation, Fast Self-Healing, analytical and NIR/pH Stimum-reactive for Multidrug-Resistant Bacterial Infection and Removable wooden Dressing [ J ]. Advanted Functional Materials,2020,30, 1910748) developed a physical Double-Network (DN) Removable Hydrogel adhesive with high Healing efficiency and antibacterial activity to address Multidrug-Resistant Bacterial infections, which Hydrogel has Rapid Self-Healing properties, good tissue adhesion, degradability, photothermal activity and assisted removal of near infrared radiation or acidic solutions for use in Wound dressings.
Disclosure of Invention
Aiming at the technical development trend and the demand of hydrogel on high strength, degradability and antibacterial performance, the invention aims to provide the high-strength degradable antibacterial hydrogel which has the characteristics of high strength, degradability and antibacterial performance and meets the use demand in the medical field.
The invention also aims to provide a preparation method of the antibacterial hydrogel.
The invention provides the following technical scheme:
the high-strength degradable antibacterial hydrogel is prepared from chitosan, multi-valence negative ions, a zwitterionic polymer and protein, wherein the zwitterionic polymer is obtained by polymerizing a zwitterionic monomer in the presence of the protein, the protein is provided with a crosslinking functional group capable of forming a chemical bond effect with the zwitterionic polymer, the zwitterionic polymer and the protein are subjected to in-situ crosslinking through the chemical bond effect to form a second crosslinking network, the chitosan and the multi-valence negative ions form a first crosslinking network through coordination, and the antibacterial hydrogel has a double-network structure formed by mutually penetrating the first network and the second network.
The antibacterial hydrogel disclosed by the invention adopts a double-network structure and has the characteristics of high strength, degradability and antibacterial property. Wherein the protein is used as a cross-linking agent in the second cross-linked network to bridge between the zwitterionic polymers, so as to realize degradability. Most of the current protein hydrogels are formed by physical interactions such as hydrophobic interactions and electrostatic interactions between protein molecules. The protein forming the protein hydrogel is directly introduced into a second network structure to react with the zwitterionic polymer, and the net forming effect in the second network is limited to the charge effect between the zwitterionic polymer and the physical effect between the zwitterionic polymer and the protein, and on one hand, the net forming effect is not strong enough, so that the strength of the antibacterial hydrogel is influenced; on the other hand, the protein in the net formation is not substantially involved in the network structure of the zwitterionic polymer, and although the protein is degraded under the degradation environment, the influence on the network structure of the zwitterionic polymer is not large, so that the real degradation of the antibacterial hydrogel cannot be realized. In consideration of the above phenomenon, the inventors of the present application introduce a crosslinking functional group capable of reacting with the zwitterionic polymer into the protein, so that the protein participates in the formation of the zwitterionic polymer network as a crosslinking agent, and bridges are formed between the zwitterionic polymers, so that the polymer network of the zwitterionic polymer is inevitably destroyed when the protein is degraded under certain conditions, thereby realizing the degradability of the antibacterial hydrogel.
Preferably, the protein is bovine serum albumin, and the crosslinking functional group is introduced into the bovine serum albumin by the following process:
dissolving bovine serum albumin in PBS buffer solution, then dripping the N, N-dimethylformamide miscible liquid of 4-dimethylaminopyridine and triethylamine into the PBS buffer solution, dripping N, N-dimethylformamide solution of methacryloyl chloride, placing the mixture into the PBS buffer solution with the concentration being reduced in sequence after magnetic stirring, carrying out step dialysis, then dialyzing in deionized water, and carrying out freeze drying to obtain the bovine serum albumin with the introduced crosslinking functional group.
The inventor introduces unsaturated double bond groups into bovine serum albumin through the treatment, can react under illumination, and creatively applies the bovine serum albumin in the formation of a zwitterionic polymerization network to provide the degradable performance of the antibacterial hydrogel.
The preferable dosage of the invention is 1-4 g, 40-500 mu L, 50-300 mg and 100-700 mu L of bovine serum albumin, 4-dimethylaminopyridine, triethylamine and methacryloyl chloride in sequence.
Preferably, the PBS buffer solution has a pH value of 7.4, and the concentrations of the PBS buffer solution used in dialysis are, from high to low, as follows: 0.2mol/L, 0.1mol/L, 0.05mol/L, 0.02mol/L and 0.01 mol/L.
Preferably, the zwitterionic monomer is at least selected from the group consisting of a sulfobetaine methyl methacrylate or a carboxylic betaine methyl methacrylate.
Preferably, the multivalent anion is selected from at least sulfate ion or citrate ion.
Preferably, the molecular weight of the chitosan is less than or equal to 10000 Da; the deacetylation degree of the chitosan is more than or equal to 90 percent.
The preparation method of the high-strength degradable antibacterial hydrogel comprises the following steps:
(1) preparing a mixed solution of chitosan, a zwitterionic monomer, protein and an initiator;
(2) removing bubbles in the mixed solution to obtain a pre-solution;
(3) sealing the pre-solution in a light-transmitting mold, deoxidizing, and then carrying out ultraviolet irradiation reaction to obtain gel;
(4) and (3) soaking the pre-gel in a solution of multivalent anions to obtain the high-strength degradable antibacterial hydrogel.
In the preparation of the mixed solution, the chitosan, the zwitterionic monomer, the protein and the initiator are dissolved in the solvent and then are uniformly stirred, the solvent can be selected from water and the like, the initiator can initiate the polymerization reaction of the zwitterionic monomer under the ultraviolet irradiation, and the alpha-ketoglutaric acid can be selected. In the preparation process, bubbles can be removed by means of ultrasonic and the like, and the removal of oxygen can be carried out by introducing nitrogen or inert gas to reduce the solubility of oxygen. The transparent grinding tool can be a glass mold or a transparent plastic mold.
Preferably, in the step (1), the concentration of the chitosan is 0.02-0.20 g/mL, the concentration of the zwitterionic monomer is 0.2-4.0 mol/L, and the concentration of the protein is 0.01-0.20 g/mL; the amount of the initiator is 0.5 to 4.0 mol% relative to the zwitterionic monomer.
Preferably, the wavelength of the ultraviolet irradiation reaction in the step (3) is 365nm, and the duration of the ultraviolet irradiation reaction is 6-8 h.
The invention has the following beneficial effects:
the antibacterial hydrogel disclosed by the invention is of a double-network structure, is obtained by mutually penetrating two cross-linked networks, has better mechanical strength and cell adhesion resistance, and good antibacterial performance, the tensile strength can reach 1.25MPa or even higher, the mechanical strength is met, the degradable performance can be realized, the antibacterial hydrogel is basically and completely degraded under the action of trypsin for about 10 days, the antibacterial hydrogel only needs two-step polymerization cross-linking reaction, and the preparation method is simple, efficient and environment-friendly.
Drawings
FIG. 1 is a stress-strain curve of hydrogels prepared with varying amounts of bovine serum albumin mBSA.
FIG. 2 is a stress-strain curve of hydrogels prepared with varying levels of sulfobetaine methylmethacrylate SBMA.
Figure 3 is a stress-strain graph of hydrogels prepared with different amounts of chitosan CS.
FIG. 4 is a fluorescence microscope image of E.coli to which the hydrogel prepared in example 2 (Panel A) and the blank control (Panel B) were attached, respectively.
Fig. 5 is a fluorescence microscope image of the hydrogel prepared in example 2 for mouse fibroblast attachment (panel C) and the blank control (panel D).
FIG. 6 is a photograph showing the degradation process of the hydrogel prepared in example 2 with trypsin (test group) and without trypsin (blank group).
In FIG. 1, curve A shows that the concentration of mBSA is 50.0mg/mL, curve B shows that the concentration of mBSA is 62.5mg/mL, curve C shows that the concentration of mBSA is 75.0mg/mL, curve D shows that the concentration of mBSA is 87.5mg/mL, and curve E shows that the concentration of mBSA is 100.0 mg/mL;
in FIG. 2, the A curve represents the SBMA concentration of 1M, the B curve represents the SBMA concentration of 2M, the C curve represents the SBMA concentration of 3M, and the D curve represents the SBMA concentration of 4M;
in FIG. 3, the A curve shows the CS concentration of 0.04g/mL, the B curve shows the CS concentration of 0.06g/mL, the C curve shows the CS concentration of 0.08mg/mL, the D curve shows the CS concentration of 0.10g/mL, and the E curve shows the CS concentration of 0.12 g/mL.
Detailed Description
The following further describes the embodiments of the present invention.
The starting materials used in the present invention are commercially available or commonly used in the art, unless otherwise specified, and the methods in the following examples are conventional in the art, unless otherwise specified.
Examples 1 to 16
A high-strength degradable antibacterial hydrogel is prepared from chitosan, multi-valence negative ions, a zwitterionic polymer and protein, wherein the zwitterionic polymer is obtained by polymerizing a zwitterionic monomer in the presence of the protein, the protein is provided with a crosslinking functional group capable of forming a chemical bond action with the zwitterionic polymer, the zwitterionic polymer and the protein are subjected to in-situ crosslinking through the chemical bond action to form a second crosslinking network, the chitosan and the multi-valence negative ions form a first crosslinking network through a coordination action, and the antibacterial hydrogel has a double-network structure formed by mutually penetrating the first network and the second network;
wherein the used zwitterionic monomer is sulfobetaine methyl methacrylate;
the deacetylation degree of the chitosan is 90%, and the average molecular weight is 8000 Da;
the multiple valence negative ions are citrate ions;
the protein used is bovine serum albumin, to which the crosslinking functional group is introduced by the following process:
1.33g bovine serum albumin BSA was dissolved in 40mL PBS buffer solution with concentration of 0.2mol/L, pH value 7.4, then 5mL N, N-dimethylformamide DMF mixed with 50mg 4-dimethylaminopyridine DMAP and 125. mu.L triethylamine TEA was added, 5mL DMF solution mixed with 80. mu.L methacryloyl chloride MAC was slowly added dropwise, magnetically stirred for 6h, and then dialyzed sequentially against 0.2mol/L, 0.1mol/L, 0.05mol/L, 0.02mol/L, 0.01mol/L PBS buffer solution with pH value 7.4, finally dialyzed against deionized water, and then freeze-dried to obtain white flocculent solid.
The preparation method of the high-strength degradable antibacterial hydrogel comprises the following steps:
(1) dissolving chitosan, a zwitterionic monomer, bovine serum albumin and an initiator in an aqueous solvent, and then uniformly stirring to obtain a mixed solution, wherein the initiator is alpha-ketoglutaric acid;
(2) ultrasonically treating the mixed solution to remove bubbles in the mixed solution to obtain a pre-solution;
(3) sealing the pre-solution in a light-transmitting mold, introducing nitrogen to reduce oxygen content and remove oxygen, and irradiating and reacting for 6 hours by using ultraviolet light with the wavelength of 365nm to obtain pre-gel;
(4) and (3) soaking the pre-gel in a citrate ion solution to obtain the high-strength degradable antibacterial hydrogel.
Specific conditions of the above examples are shown in table 1 below.
TABLE 1 conditions for carrying out examples 1 to 16
The performance of the antimicrobial hydrogels prepared in examples 1-16 above were tested as follows.
1. And (5) testing mechanical properties.
1) Preparing a hydrogel glue sample sheet: a hydrogel sample strip with the length of 40mm and the width of 10mm is prepared by a glass mold with the thickness of 1mm, and a hydrogel sample piece with the gauge length of 16mm, the width of 4mm and the thickness of 1mm is prepared by a dumbbell-shaped cutter.
2) And (3) testing tensile mechanical properties: taking the hydrogels of examples 1 to 5, 4 and 7 to 9, and 4 and 10 to 13 as examples, 3 samples of the hydrogel prepared in each example to be tested were subjected to a mechanical tensile test on an Instron 5966 universal material testing machine, the tensile speed was 100mm/min, the mechanical properties were measured, and the results were averaged.
The test results of examples 1 to 5 are shown in FIG. 1, the test results of examples 4 and 7 to 9 are shown in FIG. 2, and the test results of examples 4 and 10 to 13 are shown in FIG. 3.
As can be seen from FIG. 1, in the hydrogels prepared in examples 1 to 5, when the mBSA content gradually increases, the mechanical property curve of the hydrogel sample represented by curve A, B, C, D, E increases and then decreases, and when the mBSA content reaches 87.5mg/mL (i.e., 0.175g), the tensile strength reaches 1.25MPa at the peak and the elongation at break reaches 419.80%.
As can be seen from FIG. 2, in the hydrogels prepared in examples 4, 7 and 9, the mechanical property curve of the hydrogel sample represented by curve A, B, C, D increases and then decreases with the increase of the SBMA content, and the tensile strength of the hydrogel sample reaches the peak value of 1.25MPa when the SBMA content is 2M.
As can be seen from FIG. 3, when the CS content of the hydrogels prepared in examples 4, 10-13 increases, the tensile strength curve of the hydrogel shown by curve A, B, C, D, E increases and the elongation at break decreases accordingly.
2. And (5) testing antibacterial performance.
Taking example 2 as an example, a hydrogel sample is placed in a 12-well plate, 1mL of Escherichia coli bacterial liquid is added into each well, the Optical Density (OD) of the bacterial liquid is controlled to be 0.1, then the 12-well plate is placed in a shaking table, the sample and the bacterial liquid are co-cultured at 37 ℃ for 24h at the rotating speed of 120rpm, the sample and the bacterial liquid are stained with a staining agent for 15min under the dark condition, the adhesion condition of Escherichia coli is observed by an inverted fluorescence microscope after the sample and the phosphate buffer solution are washed, a blank control group without the hydrogel sample is arranged, and the result is shown in FIG. 4, wherein a is a hydrogel sample group, and B is a blank control group without the hydrogel sample added into the well plate.
In fig. 4, the black background is hydrogel (a) or well plate (B), and the scattered gray areas or gray spots are coliform groups, and it can be seen from fig. 4 that the coliform groups in a are less distributed compared with the blank control group B, indicating that the prepared hydrogel has a good antibacterial effect.
3. And (5) testing the cell adhesion performance.
Using example 2 as an example, a hydrogel sample after sterilization for 60min under ultraviolet light was placed in a 24-well plate, and 1mL of the hydrogel sample was added at a concentration of 5X 104Mouse fibroblast cells/mL (L929 cells)) The suspension was added to RPMI 1640 medium containing 10% fetal bovine serum for 24h, the medium was removed, and all samples were washed 5 times with PBS buffer. All samples were placed in a new 12-well plate and incubated with 5mg/mL FDA solution for 5 min. Finally, after washing with PBS buffer for 5 times, the experimental results were observed by an inverted fluorescence microscope, and the results are shown in fig. 5, in which panel C is a hydrogel sample group, and D is a blank control group to which no hydrogel sample well plate was added.
The black background area in fig. 5 is hydrogel (C) or well plate (D), and the gray area or gray dots are mouse fibroblasts, and it can be seen from fig. 5 that the background in fig. C is substantially black and there is no attachment of mouse fibroblasts, compared to the blank control D, indicating that the prepared hydrogel has low cell adhesion.
4. And (5) testing the degradation performance.
Taking example 2 as an example, two portions of hydrogel were completely swollen in PBS buffer, and then the hydrogel was taken out and placed in a twelve-well plate, one portion was immersed in PBS solution containing 0.25 wt% trypsin to prepare a test group, and the other portion was immersed in the same amount of PBS solution to prepare a blank group, and placed in a 37 ℃ shaker, shaken at 120rpm, changed every day, and changes in the mass and volume of the hydrogel were recorded, and the results are shown in FIG. 6.
As can be seen from FIG. 6, the test group showed that the hydrogel began to degrade when the volume decreased at day 4, and the hydrogel structure was substantially destroyed at day 10, indicating that the hydrogel was degraded by protease.
Example 17
A high-strength degradable antibacterial hydrogel is different from the embodiment 1 in that the concentration of chitosan is 0.02g/mL, the concentration of sulfobetaine methyl methacrylate is 0.2mol/L, and the concentration of bovine serum albumin is 0.01 g/mL; the amount of the initiator is 0.5 mol% relative to the sulfobetaine methyl methacrylate;
the introduction process of the cross-linking functional group of the bovine serum albumin is as follows: .
4g bovine serum albumin BSA was dissolved in 40mL PBS buffer solution with concentration of 0.2mol/L, pH value 7.4, then 5mL N, N-dimethylformamide DMF mixed with 300mg 4-dimethylaminopyridine DMAP and 700. mu.L triethylamine TEA was added, 5mL DMF solution mixed with 500. mu.L methacryloyl chloride MAC was slowly added dropwise, magnetically stirred for 6h, and then dialyzed sequentially against 0.2mol/L, 0.1mol/L, 0.05mol/L, 0.02mol/L, 0.01mol/L PBS buffer solution with pH value 7.4, finally dialyzed against deionized water, and then freeze-dried to obtain white flocculent solid.
Example 18
A high-strength degradable antibacterial hydrogel is different from that in example 1 in that the concentration of chitosan is 0.20g/mL, the concentration of a zwitterionic monomer is carboxylic acid betaine methyl methacrylate and is 4.0mol/L, and the concentration of bovine serum albumin is 0.20 g/mL; the amount of the initiator is 4.0 mol% relative to the sulfobetaine methyl methacrylate;
the introduction process of the cross-linking functional group of the bovine serum albumin is as follows: .
1.0g bovine serum albumin BSA was dissolved in 40mL PBS buffer solution with concentration of 0.2mol/L, pH value 7.4, then 5mL N, N-dimethylformamide DMF mixed with 50mg 4-dimethylaminopyridine DMAP and 100. mu.L triethylamine TEA was added, 5mL DMF solution mixed with 40. mu.L methacryloyl chloride MAC was slowly added dropwise, magnetically stirred for 6h, and then dialyzed sequentially against 0.2mol/L, 0.1mol/L, 0.05mol/L, 0.02mol/L, 0.01mol/L PBS buffer solution with pH value 7.4, finally dialyzed against deionized water, and then freeze-dried to obtain white flocculent solid.
Comparative example 1
The difference from example 2 is that bovine serum albumin was used without modification by introduction of a crosslinking functional group.
The maximum tensile strength of the hydrogel prepared in comparative example 1 was reduced by 20% compared to example 2, and the hydrogel was not substantially degraded after 10 days using the same degradation performance test, with an integrity retention of about 92%.
A large number of detection results show that the high-strength degradable antibacterial hydrogel prepared by the technical scheme of the invention really has excellent mechanical property, excellent cell adhesion resistance and antibacterial property, can be gradually degraded in a certain time under the action of trypsin, and has wide application prospect in the biomedical field, particularly as a bone tissue scaffold and the like.
Claims (10)
1. The high-strength degradable antibacterial hydrogel is characterized by being prepared from chitosan, multi-valence negative ions, a zwitterionic polymer and protein, wherein the zwitterionic polymer is obtained by polymerizing a zwitterionic monomer in the presence of the protein, a crosslinking functional group capable of forming a chemical bond effect with the zwitterionic polymer is arranged on the protein, the zwitterionic polymer and the protein are crosslinked in situ through the chemical bond effect to form a second crosslinking network, the chitosan and the multi-valence negative ions form a first crosslinking network through a coordination effect, and the antibacterial hydrogel has a double-network structure formed by mutually penetrating the first network and the second network.
2. The high-strength degradable antibacterial hydrogel according to claim 1, wherein the protein is bovine serum albumin, and the crosslinking functional group is introduced into bovine serum albumin by the following process:
dissolving bovine serum albumin in PBS buffer solution, then dripping the N, N-dimethylformamide miscible liquid of 4-dimethylaminopyridine and triethylamine into the PBS buffer solution, dripping N, N-dimethylformamide solution of methacryloyl chloride, placing the mixture into the PBS buffer solution with the concentration being reduced in sequence after magnetic stirring, carrying out step dialysis, then dialyzing in deionized water, and carrying out freeze drying to obtain the bovine serum albumin with the introduced crosslinking functional group.
3. The high-strength degradable antibacterial hydrogel according to claim 2, wherein the amounts of bovine serum albumin, 4-dimethylaminopyridine, triethylamine and methacryloyl chloride are 1-4 g, 40-500 μ L, 50-300 mg and 100-700 μ L in sequence.
4. The high-strength degradable antibacterial hydrogel according to claim 2 or 3, wherein the pH value of the PBS buffer solution is 7.4, and the concentration of the PBS buffer solution used in dialysis drying is from high to low in the following order: 0.2mol/L, 0.1mol/L, 0.05mol/L, 0.02mol/L and 0.01 mol/L.
5. The high-strength degradable antibacterial hydrogel according to claim 1, wherein the zwitterionic monomer is at least selected from sulfobetaine methyl methacrylate or carboxylic betaine methyl methacrylate.
6. The high-strength degradable antibacterial hydrogel according to claim 1, wherein said multivalent negative ion is at least selected from sulfate ion or citrate ion.
7. The high-strength degradable antibacterial hydrogel according to claim 1, wherein the chitosan molecular weight is less than or equal to 10000 Da; the deacetylation degree of the chitosan is more than or equal to 90 percent.
8. A method for preparing a high-strength degradable antibacterial hydrogel according to any one of claims 1 to 7, comprising the steps of:
(1) preparing a mixed solution of chitosan, a zwitterionic monomer, protein and an initiator;
(2) removing bubbles in the mixed solution to obtain a pre-solution;
(3) sealing the pre-solution in a light-transmitting mold, deoxidizing, and then carrying out ultraviolet irradiation reaction to obtain pre-gel;
(4) and (3) soaking the pre-gel in a solution of multivalent anions to obtain the high-strength degradable antibacterial hydrogel.
9. The method for preparing a high-strength degradable antibacterial hydrogel according to claim 8, wherein in the step (1), the concentration of chitosan is 0.02-0.20 g/mL, the concentration of the zwitterionic monomer is 0.2-4.0 mol/L, and the concentration of protein is 0.01-0.20 g/mL; the amount of the initiator is 0.5 to 4.0 mol% relative to the zwitterionic monomer.
10. The method for preparing the high-strength degradable antibacterial hydrogel according to claim 8, wherein the wavelength of the ultraviolet irradiation reaction in the step (3) is 365nm, and the duration of the ultraviolet irradiation reaction is 6-8 h.
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| CN113651975A (en) * | 2021-07-27 | 2021-11-16 | 浙江省医疗器械检验研究院 | Hydrogel composition, hydrogel, preparation method and application thereof |
| CN115572350A (en) * | 2022-09-29 | 2023-01-06 | 四川大学 | Degradable double-bond hyaluronic acid cross-linked zwitter-ion anti-fouling hydrogel |
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| CN115572350B (en) * | 2022-09-29 | 2024-04-19 | 四川大学 | Degradable double-bond hyaluronic acid crosslinked amphoteric ion anti-sewage gel |
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