A highly stretchable antibacterial, antioxidant and self-healing medical hydrogel and its preparation method

Abstract

The present invention belongs to the technical field of polymer material preparation, and relates to a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel and a preparation method thereof. It is formed by Schiff base crosslinking of a kaempferol guava dialdehyde B modified poly(ether-urethane) (KGPEU) and a crosslinking agent, and the crosslinking agent is an amino-terminated multi-arm polyethylene glycol. The structural formula of the KGPEU is as follows: The hydrogel provided by the present invention has excellent antioxidant, antibacterial and self-healing properties, and at the same time, the high crosslinking density endows the hydrogel with excellent tensile properties.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer material preparation, and relates to a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel and a preparation method thereof. Background Art

[0002] Disclosing the information of this background art section is only intended to increase the understanding of the overall background of the present invention, and is not necessarily regarded as an admission or an implication in any form that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] Hydrogel is a three-dimensional network polymer that can contain water but is insoluble in water and does not react with water, but can deform in an aqueous solution. According to the different gel compositions, polymer hydrogels can be divided into single-component, two-component and multi-component polymer hydrogels. Since the polymer hydrogels formed by single-component polymers often have insufficient mechanical properties and single functions, it is difficult to meet the increasingly high application requirements. In order to prepare high-performance polymer hydrogels, two-component and multi-component polymer hydrogels have gradually become the main research systems.

[0004] According to the research and understanding of the inventor, the existing medical hydrogels all have disadvantages such as a wide mutation range / poor stability control (for example, in the chemical grafting method, the grafted substance is likely to fall off), poor tensile properties, no or low antibacterial activity and antioxidant activity. It is necessary to put forward new ideas for the exploration of multifunctional medical hydrogels with high stretchability, antibacterial, antioxidant and self-healing properties. Summary of the Invention

[0005] In order to solve the deficiencies of the prior art, the purpose of the present invention is to provide a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel and a preparation method thereof. The hydrogel provided by the present invention has excellent antioxidant, antibacterial and self-healing properties, and at the same time, the high cross-linking density endows the hydrogel with excellent tensile properties.

[0006] In order to achieve the above purpose, the technical solution of the present invention is as follows:

[0007] In the first aspect of the present invention, a kaempferol guava dialdehyde B modified poly(ether-urethane) (KGPEU) is provided, and the structural formula is shown as follows:

[0008]

[0009] Wherein, R1 is R2 is R3 is n = 45 - 227.

[0010] The parentheses represent the connection position of the group.

[0011] In the present invention, a polyurethane substrate is modified by using natural polyphenol compounds and guava derivatives, and crosslinked by a multi-armed amino compound with high hydrophilicity and biocompatibility. After post-treatment, a highly stretchable antibacterial and antioxidant medical hydrogel is obtained. Since the hydrogel contains structures such as guava dialdehyde, natural polyphenols, and dynamic imine bond crosslinking, it has excellent antioxidant, antibacterial, and self-healing properties. At the same time, the high crosslinking density endows the hydrogel with excellent tensile properties.

[0012] In the second aspect of the present invention, a method for preparing kaempferol guava dialdehyde B-modified poly(ether-urethane) is provided. Polyethylene glycol (PEG), a natural dialdehyde-based dihydroxy compound, and a catalyst are dissolved in a solvent, stirred evenly, and then diisocyanate is added. Under stirring conditions, the temperature is raised to 75-85 °C for reaction to obtain an isocyanate-terminated prepolymer (GPEUP); a solution of natural polyphenol compound is added to GPEUP, and stirring is continued for heat preservation reaction to obtain the product.

[0013] In the third aspect of the present invention, an application of the above-mentioned kaempferol guava dialdehyde B-modified poly(ether-urethane) in the preparation of a highly stretchable antibacterial, antioxidant, and self-healing medical hydrogel is provided.

[0014] In the fourth aspect of the present invention, a highly stretchable antibacterial, antioxidant, and self-healing medical hydrogel is provided, which is formed by crosslinking the above-mentioned kaempferol guava dialdehyde B-modified poly(ether-urethane) with a crosslinking agent to form a Schiff base. The crosslinking agent is an amino-terminated multi-armed polyethylene glycol.

[0015] In the fifth aspect of the present invention, a method for preparing a highly stretchable antibacterial, antioxidant, and self-healing medical hydrogel is provided. A solution of kaempferol guava dialdehyde B-modified poly(ether-urethane) and a solution of amino-terminated multi-armed polyethylene glycol are mixed under the condition of 5-10 °C, and the gas is removed under reduced pressure. The polymer gel is obtained by standing for crosslinking reaction at room temperature, and the polymer gel is soaked in deionized water and the water is changed regularly to obtain the product.

[0016] In the sixth aspect of the present invention, an application of the above-mentioned highly stretchable antibacterial, antioxidant, and self-healing medical hydrogel in the field of biomedical engineering is provided.

[0017] The hydrogel of the present invention has a high crosslinking degree, thus endowing it with excellent tensile properties. At room temperature, the tensile strength of the medical hydrogel is higher than 0.35 MPa, and the elongation at break is higher than 400%.

[0018] The medical hydrogel of the present invention has good free radical scavenging ability and exhibits good antioxidant properties.

[0019] The hydrogel of the present invention is crosslinked by the reaction of aldehyde groups with amino groups to form imine bonds, and the dynamic imine bonds endow the hydrogel with good self-healing performance. This hydrogel has good room-temperature self-healing performance, and the healing efficiency can reach 99.8% after self-healing for 2 h at room temperature.

[0020] The medical hydrogel of the present invention has good inhibitory effects on both Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), indicating that this medical hydrogel has high broad-spectrum antibacterial activity.

[0021] The hydrogel of the present invention also has good biocompatibility and biodegradability, and thus can be widely applied in the biomedical field.

[0022] The beneficial effects of the present invention are as follows:

[0023] (1) The hydrogel provided by the present invention has excellent antioxidant activity. The introduced dialdehyde dihydroxy compound (guava dialdehyde B) is an antioxidant active substance and a natural organic matter extracted from plants, so it has good metabolic and absorption effects on the body and has no negative effects.

[0024] (2) The introduction of natural broad-spectrum antibacterial polyphenol (tannic acid) endows the hydrogel of the present invention with good antibacterial activity.

[0025] (3) The hydrogel of the present invention is crosslinked by polyaldehyde groups and polyamino groups. This crosslinking reaction can quickly react at low temperature or room temperature without any catalyst, avoiding problems such as uneven crosslinking network caused by low crosslinking degree. The formed molecular network has a uniform size, can disperse the force evenly when stressed, and has no defects, so it has excellent tensile properties.

[0026] (4) The hydrogel of the present invention is crosslinked by multiple imine bonds. The dynamic imine bonds can be broken and recombined at room temperature, thus endowing the hydrogel with good room-temperature self-healing performance.

[0027] (5) The hydrogel of the present invention uses highly biocompatible synthetic materials and natural materials as raw materials. Therefore, the prepared hydrogel has excellent biocompatibility and good biodegradability, and this multifunctional hydrogel can be arbitrarily cut or formed with different molds, is easy to use, and can be widely applied in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The specification drawings forming a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation to the present invention.

[0029] Figure 1Bar chart of DPPH radical scavenging rates of PU-PEG-WG1, PU-PEG-WG2, and PU-PEG-WG3 in the embodiments of the present invention.

[0030] Figure 2 Schematic diagram of the sizes of the inhibition zone diameters of PU-PEG-WG1, PU-PEG-WG2, and PU-PEG-WG3 against S. aureus and E. coli in the embodiments of the present invention.

[0031] Figure 3 Bar chart of the cell proliferation rates of PU-PEG-WG1, PU-PEG-WG2, and PU-PEG-WG3 in the embodiments of the present invention. Detailed implementation manners

[0032] It should be noted that the following detailed description is exemplary and is intended to provide further illustration of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0033] It should be noted that the terms used herein are only for describing specific implementation manners and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0034] As introduced in the background art, existing medical hydrogels all have disadvantages such as a wide mutation range / poor stability control, poor tensile properties, no or low antibacterial and antioxidant activities. The present invention proposes a highly stretchable antibacterial, antioxidant, and self-healing medical hydrogel and its preparation method.

[0035] A typical embodiment of the present invention provides a kaempferol guava dialdehyde B-modified poly(ether-urethane) with the following structural formula:

[0036]

[0037] Among them, R1 is R2 is R3 is n = 45 - 227.

[0038] Another embodiment of the present invention provides a method for preparing kaempferol guaiacyl dialdehyde B-modified poly(ether-urethane). Polyethylene glycol (PEG), a natural dialdehyde-containing dihydroxy compound, and a catalyst are dissolved in a solvent, stirred evenly, and then diisocyanate is added. Under stirring conditions, the temperature is raised to 75-85 °C for reaction to obtain an isocyanate-terminated prepolymer (GPEUP); a solution of a natural polyphenol compound is added to the kaempferol guaiacyl dialdehyde B-modified poly(ether-urethane), and stirring is continued for heat preservation reaction to obtain the product.

[0039] In some embodiments, the number-average molecular weight of polyethylene glycol is 2000-20000 g / mol, preferably 2000-10000 g / mol.

[0040] In some embodiments, the diisocyanate is an aliphatic diisocyanate, preferably lysine diisocyanate.

[0041] In some embodiments, the natural dialdehyde-containing dihydroxy compound is guaiacyl dialdehyde, preferably guaiacyl dialdehyde B (GDB).

[0042] In some embodiments, the molar ratio of polyethylene glycol, the natural dialdehyde-containing dihydroxy compound, and diisocyanate is 1:1:3.

[0043] In some embodiments, the solvent is N,N-dimethylformamide (DMF), N,N-dimethylacetamide, or dimethyl sulfoxide; preferably DMF.

[0044] In some embodiments, the mass concentration of the raw materials in the solvent is 0.5-1.0 g / mL.

[0045] In some embodiments, the catalyst is a tin-based catalyst. Preferably, the catalyst is dibutyltin dilaurate or stannous octoate.

[0046] In some embodiments, the addition amount of the catalyst is 0.1-1% of the total mass of polyethylene glycol, the natural dialdehyde-containing dihydroxy compound, and diisocyanate.

[0047] In some embodiments, the reaction end point of GPEUP is detected by the dibutylamine method for the isocyanate group content until the isocyanate group content reaches the theoretical value, and the reaction time is 1.5-3 h.

[0048] In some embodiments, the solution concentration of GPEUP in the solvent is 0.50-0.65 g / mL.

[0049] In some embodiments, the natural polyphenol compound is catechin, tannic acid, kaempferol, and quercetin, preferably kaempferol.

[0050] In some embodiments, the concentration of the solution of the natural polyphenol compound is 0.45 - 0.55 g / mL. The solvent is the same solvent as that in the preparation of GPEUP.

[0051] In some embodiments, the addition amount of the natural polyphenol compound is 1.01 - 1.05 times the molar amount of isocyanate groups in PEGUP.

[0052] In some embodiments, the reaction end point of the kaempferol guava dialdehyde B-modified poly(ether-urethane) is the disappearance of the isocyanate group absorption peak in the infrared detection system, which is 1.5 - 2.5 h.

[0053] The third embodiment of the present invention provides an application of the above-mentioned kaempferol guava dialdehyde B-modified poly(ether-urethane) in the preparation of a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel.

[0054] The fourth embodiment of the present invention provides a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel, which is formed by cross-linking the above-mentioned kaempferol guava dialdehyde B-modified poly(ether-urethane) with a cross-linking agent to form a Schiff base. The cross-linking agent is amino-terminated multi-arm polyethylene glycol.

[0055] In some embodiments, the amino-terminated multi-arm polyethylene glycol is amino-terminated four-arm polyethylene glycol (4-arm-PEG-NH2). The number average molecular weight is 2000 - 20000 g / mol, and the chemical structural formula is as follows:

[0056]

[0057] The fifth embodiment of the present invention provides a preparation method of a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel. The solution of the kaempferol guava dialdehyde B-modified poly(ether-urethane) and the solution of the amino-terminated multi-arm polyethylene glycol are mixed under the condition of 5 - 10 °C, the gas is removed by pressurization, and the cross-linking reaction is carried out by standing at room temperature to obtain a polymer gel. The polymer gel is soaked in deionized water and the water is changed regularly to obtain the hydrogel.

[0058] In some embodiments, the concentration of the solution of the kaempferol guava dialdehyde B-modified poly(ether-urethane) is 0.3 - 0.4 g / mL. The solvent is preferably DMF.

[0059] In some embodiments, the concentration of the solution of the amino-terminated multi-arm polyethylene glycol is 1 - 3 g / mL. The solvent is preferably DMF.

[0060] In some embodiments, the molar ratio of the aldehyde group in the kaempferol guava dialdehyde B-modified poly(ether-urethane) to the amino group of the amino-terminated multi-arm polyethylene glycol is 1:0.9 - 1:1.1.

[0061] In some embodiments, the cross-linking reaction time at room temperature is 6 to 12 h.

[0062] In some embodiments, the polymer gel is immersed in deionized water for 7 to 14 days, and the water is changed every 12 h.

[0063] The sixth embodiment of the present invention provides an application of the above-mentioned highly stretchable antibacterial, antioxidant and self-healing medical hydrogel in the field of biomedical engineering. Preferably, it is used as an in vivo implant material.

[0064] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with specific embodiments.

[0065] Example 1

[0066] Dissolve 5.0 g of polyethylene glycol (M n = 2000 g / mol), 1.2 g of guava dialdehyde B (GDB) and 0.01 g of dibutyltin dilaurate in 13 mL of DMF solvent, stir evenly, add 1.7 g of lysine diisocyanate (LDI), and under mechanical stirring, heat up to 80 °C and react for 2 h to obtain an isocyanate-terminated prepolymer (GPEUP) solution (concentration: 0.61 g / mL). Then add 1.5 mL of a DMF solution of kaempferol (0.5 g / mL) to the system, and continue to react at a constant temperature for 2.5 h under mechanical stirring to obtain a solution of KGPEU (0.60 g / mL).

[0067] Mix 25 mL of the DMF solution of KGPEU (0.34 g / mL) with 5 mL of the DMF solution of amino-terminated tetra-arm polyethylene glycol (M n = 2000 g / mol) (1.0 g / mL) at 5 °C, stir quickly and evenly, remove the gas under reduced pressure, and let it stand at room temperature for cross-linking reaction for 6 h to obtain a polymer gel (PU-PEG-G1); Immerse the prepared gel in deionized water for 14 days, and change the water regularly every 12 h to obtain a medical hydrogel, denoted as PU-PEG-WG1.

[0068] Example 2

[0069] Dissolve 25.0 g of polyethylene glycol (M n5000 g / mol), 2.37 g of guava dialdehyde B (GDB), and 0.02 g of dibutyltin dilaurate were dissolved in 56 mL of DMF solvent, stirred evenly, 3.4 g of lysine diisocyanate (LDI) was added, and under mechanical stirring, the temperature was raised to 80 °C and reacted for 2 h to obtain an isocyanate-terminated prepolymer (GPEUP) solution (concentration: 0.55 g / mL). Then, 2.9 mL of a DMF solution of kaempferol (0.5 g / mL) was added to the system, and the reaction was continued under mechanical stirring and heat preservation for 2.5 h to obtain a solution of KGPEU (0.62 g / mL).

[0070] 108 mL of a DMF solution of KGPEU (0.34 g / mL) was mixed with 25 mL of an amino-terminated tetra-armed polyethylene glycol (M n = 5000 g / mol) in a DMF solution (1.0 g / mL) at 8 °C, stirred quickly and evenly, the gas was removed under reduced pressure, and the mixture was left to stand at room temperature for crosslinking reaction for 9 h to obtain a polymer gel (PU-PEG-G2); the prepared gel was soaked in deionized water for 10 days, and the water was changed regularly every 12 h to obtain a medical hydrogel, denoted as PU-PEG-WG2.

[0071] Example 3

[0072] 50.0 g of polyethylene glycol (M n = 10000 g / mol), 2.37 g of guava dialdehyde B (GDB), and 0.02 g of stannous octoate were dissolved in 105 mL of DMF solvent, stirred evenly, 5.1 g of lysine diisocyanate (LDI) was added, and under mechanical stirring, the temperature was raised to 80 °C and reacted for 2 h to obtain an isocyanate-terminated prepolymer (GPEUP) solution (concentration: 0.55 g / mL). 4.35 mL of a DMF solution of kaempferol (0.5 g / mL) was added to GPEUP, and the reaction was continued under mechanical stirring and heat preservation for 2.5 h to obtain a solution of KGPEU (0.60 g / mL).

[0073] 195 mL of a DMF solution of KGPEU (0.34 g / mL) was mixed with 75 mL of an amino-terminated tetra-armed polyethylene glycol (M n = 10000 g / mol) in a DMF solution (1.0 g / mL) at 10 °C, stirred quickly and evenly, the gas was removed under reduced pressure, and the mixture was left to stand at room temperature for crosslinking reaction for 12 h to obtain a polymer gel (PU-PEG-G3); the prepared gel was soaked in deionized water for 8 days, and the water was changed regularly every 12 h to obtain a medical hydrogel, denoted as PU-PEG-WG3.

[0074] Analysis and Explanation

[0075] The following analysis methods were used for all examples unless otherwise stated.

[0076] Self-healing performance: Cut the polymer elastomer. The cut elastomers are brought into contact along the cut cross-section and self-healed at room temperature for 2 h. Tensile tests are performed on the healed splines and compared with the original samples. The self-healing efficiency is expressed by the following two expressions: R(σ) = σ healed / σ initial , where σ healed and σ initial are the tensile strengths of the healed and original samples, respectively.

[0077] Tensile performance: Tensile splines of the polymer elastomer are prepared using a rubber pneumatic slicing machine. The splines are 8 cm long and 1.5 cm wide. Tensile property tests are performed on the specimens using a Zwick / Roell / 005 type electronic universal material testing machine (Zwick / Roell Company, Germany) at a tensile speed of 500 mm / min.

[0078] Antioxidant performance is determined by the DPPH free radical scavenging ability: Dissolve DPPH (1,1-diphenyl-2-picrylhydrazyl) in a small amount of absolute ethanol, and then prepare a 0.1 mg / mL solution using 80% ethanol as the solvent. Transfer 0.05 mL of each concentration of the sample solution to be tested to 2.95 mL of the DPPH solution. At this time, the total volume is 3 mL. After shaking well, heat it in a water bath at 25 °C. After 30 min, measure its absorbance at 517 nm. The calculation formula for the scavenging rate of DPPH is:

[0079] DPPH free radical scavenging rate (%) = (A0 - A1 - A2) / A0 × 100;

[0080] where A0 is the absorbance of the DPPH solution + 80% ethanol, A1 is the absorbance of the DPPH solution plus the sample, and A2 is the absorbance of the sample + 80% ethanol.

[0081] Antibacterial performance: The antibacterial test is performed using the antibacterial zone method. Cut the membrane material into circular membrane pieces with a diameter of 0.5 ± 0.01 mm using a punch and sterilize them by ultraviolet lamp irradiation. Use the original piece of the ordinary membrane material for the experiment. Take the purified and cultured Escherichia coli and Staphylococcus aureus and place them in a beef extract peptone liquid medium. Observe in a constant temperature incubator at 37 °C for 24 h to obtain a bacterial suspension; Dilute 50 μL of the bacterial suspension with PBS solution to 3×10 5 ~5×10 6CFUs / mL. The bacterial suspension was placed in a sterile petri dish containing solid (agar) medium, and the bacterial liquid was spread to evenly inoculate the surface of the medium. Then, the tested membrane was attached to the petri dish inoculated with Escherichia coli or Staphylococcus aureus. The medium with the tested sample was placed in an incubator at 37 °C and incubated upside down for 24 h. After the colonies grew, it was taken out for observation, and the diameter of the antibacterial circle produced by the sample was measured. The antibacterial activity of the material was judged by the size of the antibacterial circle.

[0082] Cell viability: The membrane material was cut into circular membrane pieces with a diameter of 0.5 ± 0.01 mm using a puncher. After sterilization under ultraviolet light, it was placed into a 96-well plate, and 3 replicates were set for each group. The L-929 mouse fibroblasts were diluted and configured into a cell suspension with a concentration of about 2×10 5 cells / mL. 210 μL of the cell suspension was inoculated into each well. Four plates were taken, and after culturing for 72 h respectively, the MTT method was used to measure the cell proliferation rate after treating the samples. The cytotoxicity of the material was judged by the scoring result of the cell survival rate. The cell viability was calculated according to the following formula:

[0083] Cell Viability(%) = (A sample - A blank ) / (A control - A blank ) × 100%

[0084] where, A sample and A control are the absorbances after treatment, and A blank is the absorbance of the blank control.

[0085] Cell Viability ≥ 75% is considered to have good cell compatibility and can be used as an in vivo biomaterial. Cell Viability < 50 is considered to have a cytotoxic reaction.

[0086] Table 1 Relationship between self-healing efficiency and number of repair times (room temperature repair for 2 h)

[0087]

[0088] It can be seen from Table 1 that the self-healing efficiency of the hydrogel prepared in this patent is still higher than 85% after repeated repair six times, indicating that the gel has good room temperature self-healing performance and can be repeatedly repaired.

[0089] Table 2 Tensile property characteristic values of the hydrogel PU-PEG-WG

[0090] <![CDATA[PU-PEG-WG1]]> <![CDATA[PU-PEG-WG2]]> <![CDATA[PU-PEG-WG3]]> Elongation at break / % 435.2 456.8 463.5 Tensile strength / MPa 0.41 0.38 0.36

[0091] As can be seen from Table 2, the elongation at break of the hydrogel prepared by this patent is higher than 430%, and the tensile strength is higher than 0.36 MPa, indicating that the gel has good tensile properties and mechanical strength.

[0092] From Figure 1 it can be seen that the DPPH radical scavenging rate of the medical hydrogel of this patent is higher than 90%, indicating that the medical hydrogel has good antioxidant properties.

[0093] The antibacterial effect is as Figure 2 shown. From Figure 2 it can be seen that the medical hydrogel prepared by this patent has good antibacterial properties, and its antibacterial effect against Gram-positive bacteria (S.aures) is better than that against Gram-negative bacteria (E.coil). Thus, it can be known that the hydrogel has good broad-spectrum antibacterial activity.

[0094] The cell activity effect is as Figure 3 shown. From Figure 3 it can be seen that the cell proliferation rate of the medical hydrogel prepared by this patent is higher than 75%, and the cytotoxicity is Class I, indicating that it has good cell compatibility and can be used as an in vivo implant material.

[0095] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A highly stretchable antibacterial and antioxidant self-healing medical hydrogel, characterized in that, The poly(ether-urethane) modified by kaempferol guava dialdehyde B is formed by cross-linking with a cross-linking agent through the formation of Schiff base. The cross-linking agent is amino-terminated tetra-armed polyethylene glycol; The structural formula of the poly(ether-urethane) modified by kaempferol guava dialdehyde B is as follows: wherein, R1 is ; R2 is ; R3 is ; n = 45 to 227.

2. The highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to claim 1, characterized in that, The preparation method of the poly(ether-urethane) modified by kaempferol guava dialdehyde B includes: dissolving polyethylene glycol, a natural dialdehyde dihydroxy compound and a catalyst in a solvent, stirring evenly, adding diisocyanate, and under stirring conditions, heating to 75-85 °C for reaction to obtain an isocyanate-terminated prepolymer; adding a solution of a natural polyphenol compound to the GPEUP, and stirring to continue the heat preservation reaction to obtain it.

3. The highly stretchable antibacterial and antioxidant self-healing medical hydrogel according to claim 2, characterized in that, The number-average molecular weight of polyethylene glycol is 2000-20000 g / mol; Or, the molar ratio of polyethylene glycol, the natural dialdehyde dihydroxy compound, and diisocyanate is 1:1:3; Or, the solvent is N,N-dimethylformamide, N,N-dimethylacetamide or dimethyl sulfoxide; Or, the catalyst is a tin-based catalyst; Or, the addition amount of the catalyst is 0.1-1% of the total mass of polyethylene glycol, the natural dialdehyde dihydroxy compound and diisocyanate; Or, the concentration of the solution of the natural polyphenol compound is 0.45-0.55 g / mL; Or, the addition amount of the natural polyphenol compound is 1.01-1.05 times the molar amount of isocyanate groups in the isocyanate-terminated prepolymer.

4. The highly stretchable antibacterial and antioxidant self-healing medical hydrogel according to claim 3, characterized in that, The number-average molecular weight of polyethylene glycol is 2000-10000 g / mol.

5. The highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to claim 3, characterized in that, The solvent is N,N-dimethylformamide.

6. The highly stretchable antibacterial and antioxidant self-healing medical hydrogel according to claim 3, wherein The catalyst is dibutyltin dilaurate or stannous octoate.

7. A preparation method of a highly stretchable antibacterial, antioxidant and self-healing medical hydrogel, characterized in that, The solution of the poly(ether-urethane) modified by kaempferol guava dialdehyde B is cross-linked with a cross-linking agent through the formation of Schiff base. The cross-linking agent is amino-terminated tetra-armed polyethylene glycol. The solution of amino-terminated multi-armed polyethylene glycol is mixed under the condition of 5-10 °C, the gas is removed under pressure, and the cross-linking reaction is carried out by standing at room temperature to obtain a polymer gel. The polymer gel is soaked in deionized water and the water is changed regularly to obtain it; The structural formula of the poly(ether-urethane) modified by kaempferol guava dialdehyde B is as follows: Among them, R1 is ; R2 is ; R3 is ; n = 45 to 227.

8. The preparation method of the highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to claim 7, characterized in that, The concentration of the solution of the poly(ether-urethane) modified by kaempferol guava dialdehyde B is 0.3-0.4 g / mL; Or, the concentration of the solution of amino-terminated multi-armed polyethylene glycol is 1-3 g / mL; Or, the molar ratio of the aldehyde groups in the poly(ether-urethane) modified by kaempferol guava dialdehyde B to the amino groups of amino-terminated multi-armed polyethylene glycol is 1:0.9-1.1; Or, the cross-linking reaction time by standing at room temperature is 6-12 h; Or, the polymer gel is soaked in deionized water for 7-14 days, and the water is changed every 12 h.

9. The preparation method of the highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to claim 8, characterized in that, The concentration of the solution of the poly(ether-urethane) modified by kaempferol guava dialdehyde B is 0.3-0.4 g / mL; the solvent is N,N-dimethylformamide.

10. The preparation method of the highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to claim 8, characterized in that, The concentration of the solution of amino-terminated multi-armed polyethylene glycol is 1-3 g / mL; the solvent is N,N-dimethylformamide.

11. Use of the highly stretchable antibacterial, antioxidant and self-healing medical hydrogel according to any one of claims 1-6, or the highly stretchable antibacterial, antioxidant and self-healing medical hydrogel prepared by the preparation method according to any one of claims 7-10, in the preparation of an in-vivo implant material.

Images