Amphoteric ion hydrogel coating with bacterial responsiveness and antifouling performance and preparation method thereof
阅读说明：本技术 一种具有细菌响应性防污的两性离子水凝胶涂层及其制备方法 (Amphoteric ion hydrogel coating with bacterial responsiveness and antifouling performance and preparation method thereof ) 是由 张静 吴敏敏 彭湃 罗鑫鑫 于 2021-06-30 设计创作，主要内容包括：本发明涉及高分子水凝胶技术领域,尤其涉及一种具有细菌响应性防污的两性离子水凝胶涂层及其制备方法,所述水凝胶涂层中含有透明质酸,所述水凝胶涂层为两性离子聚合物且聚合物分子链上同时带有阴、阳离子基团。本发明的制备方法简洁、高效且环保,对环境友好；水凝胶涂层和聚合物基底之间形成界面互穿牢固结合,具有一定的结合力和较低摩擦系数,在细菌分泌透明质酸酶的情况下使涂层降解脱落达到抗细菌黏附的效果；在去离子水中能够长期保存；具有优异的亲水性、抗弯折性能以及耐摩擦性能,在生物医用表面材料领域,尤其是作为医用导管表面涂层等方面具有广阔的应用前景。(The invention relates to the technical field of high-molecular hydrogel, in particular to a bacterial-responsive antifouling zwitter-ion hydrogel coating and a preparation method thereof. The preparation method is simple, efficient, environment-friendly and environment-friendly; interface interpenetration and firm combination are formed between the hydrogel coating and the polymer substrate, the hydrogel coating has certain binding force and lower friction coefficient, and the coating is degraded and shed under the condition that bacteria secrete hyaluronidase to achieve the effect of resisting bacterial adhesion; can be stored in deionized water for a long time; has excellent hydrophilicity, bending resistance and friction resistance, and has wide application prospect in the field of biomedical surface materials, in particular as medical catheter surface coatings and the like.)
1. The amphoteric ion hydrogel coating with the bacterial response antifouling function is characterized by comprising hyaluronic acid, wherein the hydrogel coating is a amphoteric ion polymer, and the molecular chain of the polymer simultaneously carries anionic and cationic groups.
2. A preparation method of a zwitter-ion hydrogel coating with bacterial response and antifouling performance is characterized by comprising the following preparation steps:
1) grafting methacrylamide on hyaluronic acid;
2) soaking the polymer substrate under a hydrophobic initiator after the oxygen plasma treatment;
3) preparing a mixed solution of a zwitterion monomer, hyaluronic acid, N' -methylene bisacrylamide and an initiator;
4) deoxidizing the mixed solution, and removing bubbles in the mixed solution to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for a period of time;
6) and (3) after the standing polymer substrate is subjected to reaction under ultraviolet irradiation, ultrasonically cleaning to remove the non-crosslinked hydrogel coating, and obtaining the uniform bacterial-responsive antifouling zwitter-ion hydrogel coating after the reaction is finished.
3. The method according to claim 2, wherein in the step 1): hyaluronic acid molecular weight less than 5000;
and/or the grafting rate of the hyaluronic acid is 65-75%.
4. The method according to claim 2, wherein in the step 2): the oxygen plasma treatment time is 0.5-5 min;
and/or the hydrophobic initiator is a benzophenone methanol or isopropanol solution, and the soaking time is 5-240 min.
5. The method according to claim 2, wherein in the mixed solution of step 3): the concentration of the zwitterionic monomer is 0.1-4.0 mol/L;
and/or the concentration of hyaluronic acid is 0.4-0.8 mol% relative to the zwitterionic monomer;
and/or the concentration of N, N' -methylene bisacrylamide is 0.01-0.20 mol% relative to the zwitterionic monomer;
and/or the amount of the initiator is 0.5-4.0 mol% relative to the zwitterionic monomer;
and/or the preparation process is that the zwitterion monomer, the hyaluronic acid, the N, N' -methylene bisacrylamide and the initiator are dissolved in the solvent and then are stirred uniformly.
6. The method of claim 5, wherein the solvent comprises water.
7. The production method according to claim 2, 5 or 6, wherein in the step 3): the initiator comprises alpha-ketoglutaric acid;
and/or the zwitterionic monomer comprises one or both of sulfobetaine methyl methacrylate and carboxylic betaine methyl methacrylate.
8. The method according to claim 2, wherein in the step 4): deoxygenation is carried out by introducing nitrogen or inert gas to reduce oxygen solubility;
and/or the method for removing bubbles in the mixed solution is ultrasonic.
9. The preparation method according to claim 2, wherein the standing time in the step 5) is 0 to 60 min.
10. The method according to claim 2, wherein in the step 6): the ultraviolet wavelength is 350-380 nm, and the irradiation time is 3-8 h;
and/or the ultrasonic cleaning time is 0.5-2 h.
Technical Field
The invention relates to the technical field of high-molecular hydrogel, in particular to a bacterial-responsive antifouling zwitter-ion hydrogel coating and a preparation method thereof.
Background
In the biomedical field, biological contamination is very likely to occur on instruments and devices such as sensors, interventional catheters or bone materials, thereby causing inflammatory reactions, rejection reactions and the like. Meanwhile, medical equipment is widely applied and is often in complex environments such as blood, body fluid and the like, and biological pollution formed in the field is mainly generated by thrombus and bacterial membranes, so that the life safety of a patient is greatly threatened. The biological contamination is developed through the adsorption of protein on the surface of material to form one protein layer, and the adhesion of bacteria, blood cell, etc. to result in bacterial infection, thrombus, etc. The antibacterial and anti-adhesive properties of hydrogel coatings for biomedical applications are essential to avoid bacterial infections. Kisuk Yang et al used a catechol-functionalized polymer hydrogel membrane to prepare a robust low-friction antibiotic coating on urethral catheters. A stable chitosan hydrogel coating of micron-scale thickness was formed on a substrate using catechol-conjugated chitosan solution in a weakly basic buffer using a simple dip coating process. The Hydrogel Coating can reduce surface Friction, and incorporation of antibacterial silver nanoparticles into the Hydrogel can minimize bacterial binding on the catheter surface by simply adding a silver nitrate solution Using conjugated Catechol groups as a reducing agent (Kisuk Yang, Kyuri Kim, Eujee A.Lee, et al, Robust Low Collection antibacterial Coating of organic catalysts a protective-Functionalized Polymeric Hydrogel films [ J ]. Frontiers in Materials,2019,6: 274.).
Hyaluronic Acid (HA) is a natural polysaccharide, whose repeating units consist of D-glucuronic acid and N-acetylglucosamine, and is a key component of the extracellular matrix. Because the bacteria secrete hyaluronidase, the bacteria on the surface can be degraded and shed along with the HA layer after reacting with the substrate hyaluronic acid, and the unique responsiveness enables the hyaluronic acid to have great potential to be used for treating occasions with antibacterial adhesion. Pirah Ayaz et al developed a layer-by-layer assembled antimicrobial controlled-release multilayer surface based on polyacrylic acid and chitosan quaternary ammonium salt. In which Gentamicin Sulphate (GS) was added in multiple layers and hyaluronic acid was used as a top sealing layer. During bacterial attack, the pH value of the microenvironment is slightly increased, and the multilayer film can release the medicine after swelling. Meanwhile, hyaluronidase (HAase) secreted by bacteria triggers HA layer degradation to accelerate GS release and exert antibacterial activity. The Surface exhibits high antibacterial activity against both gram-positive and gram-negative bacteria (Pirah Ayaz, Bingjie Xu, Xiansheng Zhang, et al ApH and hyaluronic dual-reactive multi-layer-based delivery system for retaining bacterial infection [ J ]. Applied Surface Science,2020,527: 146806.).
However, the preparation of the multi-layer sustained-release surface is complicated, and the hydrogel coating or the hyaluronic acid layer is easily peeled off due to the influence of environmental factors, so that the antibacterial performance is reduced and the antibacterial time is shortened.
Disclosure of Invention
The invention aims to overcome the defects of complex preparation process and low stability in the prior art, and provides a bacterial-responsive antifouling zwitterionic hydrogel coating and a preparation method thereof, which realize the following purposes: firstly, a certain flow is explored, so that the preparation process is simpler and more efficient. Formulation of a cohesive hydrogel coating; secondly, the hydrogel coating is degraded under the action of bacterial secretion hyaluronidase to prevent bacterial adhesion and have bacterial responsiveness; thirdly, the hydrogel coating has excellent stability and mechanical properties; fourthly, the preparation is simplified.
In order to achieve the purpose, the invention adopts the following technical scheme:
the amphoteric ion hydrogel coating with the bacterial response antifouling function contains hyaluronic acid, is an amphoteric ion polymer and simultaneously carries anionic and cationic groups on a polymer molecular chain.
The hyaluronic acid contained in the hydrogel coating can degrade the hydrogel coating under the condition that bacteria secrete hyaluronidase, and after the hydrogel coating is degraded, the bacteria and other microorganisms fall off along with the degraded coating, so that the adhesion of the bacteria and proteins can be effectively prevented. The hydrogel coating is a zwitterionic polymer, and the molecular chain of the polymer is simultaneously provided with anionic groups and cationic groups, so that the hydrogel coating can be strongly combined with water molecules through solvation to generate repulsive force, and can effectively resist the adhesion of proteins or bacteria and cells.
A zwitter-ion hydrogel coating with bacterial response and antifouling performance is prepared by the following method:
1) grafting methacrylamide on hyaluronic acid;
2) soaking the polymer substrate under a hydrophobic initiator after the oxygen plasma treatment;
3) preparing a mixed solution of a zwitterion monomer, hyaluronic acid, N' -methylene bisacrylamide and an initiator;
4) deoxidizing the mixed solution, and removing bubbles in the mixed solution to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for a period of time;
6) and (3) after the standing polymer substrate is subjected to reaction under the irradiation of ultraviolet light through a light-transmitting mold, removing the non-crosslinked hydrogel coating through ultrasonic cleaning, and obtaining the uniform bacterial-responsive antifouling zwitter-ion hydrogel coating after the reaction is finished.
According to the invention, after the methacrylamide is grafted on the hyaluronic acid, the amphoteric ion monomer, the hyaluronic acid and the N, N' -Methylene Bisacrylamide (MBA) react with the polymer substrate under the action of the initiator under a certain condition, so that the polymer substrate is grafted with the elastic network of the hydrogel in a covalent bond mode under the soaking of the hydrophobic initiator, and thus, an interface interpenetrating is formed between the hydrogel coating containing the hyaluronic acid and the polymer substrate and is firmly combined together, and the hydrogel coating has a certain binding force and a lower friction coefficient, so that the hydrogel coating has good stability and can be stored for a long time. Specifically, the prepared zwitterionic hydrogel coating can prevent bacteria from adhering for 132 hours under the bacterial response action, and the bacteria still have less adhesion in 132 hours; and/or no significant change in storage time in deionized water of 2 months; and/or no cracks after 150 folds; and/or the water contact angle does not change much 400 rubs.
Preferably, in the step 1): hyaluronic acid molecular weight less than 5000; and/or the grafting rate of the hyaluronic acid is 65-75%. The hyaluronic acid with too high molecular weight may cause partial degradation and not timely shedding together with bacteria thereon after being subjected to hyaluronidase secreted by the bacteria, resulting in a decrease in the effect of preventing bacterial adhesion according to the present invention.
Preferably, in the step 2): the polymer substrate is PDMS; and/or the oxygen plasma treatment time is 0.5-5 min; and/or the hydrophobic initiator is a benzophenone methanol or isopropanol solution, and the soaking time is 5-240 min;
preferably, in the mixed solution of step 3): the concentration of the zwitterionic monomer is 0.1-4.0 mol/L; and/or the concentration of hyaluronic acid is 0.4-0.8 mol% relative to the zwitterionic monomer; and/or the concentration of N, N' -methylene bisacrylamide is 0.01-0.20 mol% relative to the zwitterionic monomer; and/or the amount of the initiator is 0.5-4.0 mol% relative to the zwitterionic monomer; and/or the preparation process is that the zwitterion monomer, the hyaluronic acid, the N, N' -methylene bisacrylamide and the initiator are dissolved in the solvent and then are stirred uniformly.
Preferably, the solvent comprises water.
Preferably, in the step 3): the initiator comprises alpha-ketoglutaric acid; and/or the zwitterionic monomer comprises one or both of sulfobetaine methyl methacrylate and carboxylic betaine methyl methacrylate. The sulfobetaine methyl methacrylate (SBMA) and the carboxylic betaine methyl methacrylate (CBMA) can be grafted on the polymer molecular chain in subsequent reaction to combine water molecules and generate repulsion, wherein the zwitterionic monomer is preferably the sulfobetaine methyl methacrylate (SBMA).
Preferably, in the step 4): deoxygenation is carried out by introducing nitrogen or inert gas to reduce oxygen solubility; and/or the method for removing bubbles in the mixed solution is ultrasonic.
Preferably, the standing time in the step 5) is 0-60 min. The uniform dripping in the step 5) can ensure the size of the polymer substrate and the volume of the dripping pre-polymerization liquid to be consistent, and the standing time can be adjusted within 0-60 minutes according to the mixing effect and the uniformity.
Preferably, in the step 6): the light-transmitting mold comprises a glass mold; and/or the wavelength of the ultraviolet light is 350-380 nm, and the irradiation time is 3-8 h; and/or the ultrasonic cleaning time is 0.5-2 h.
In conclusion, the invention has the following beneficial effects: the preparation method is simple, efficient, environment-friendly and environment-friendly; the hydrogel coating is prepared from zwitterions, MBA and hyaluronic acid, the elastic network of the hydrogel is covalently grafted when the polymer substrate is soaked in a hydrophobic initiator, and the hydrogel coating and the polymer substrate form interfacial interpenetrating firm combination; can be stored in deionized water for a long time; has excellent hydrophilicity, bending resistance and friction resistance.
Drawings
FIG. 1 shows that Staphylococcus aureus prepared in example 4 of the present invention was attached to (A)1～A3) Hydrogel coated PDMS and (B)1～B3) Fluorescence microscopy images on PDMS.
Fig. 2 is a field emission electron microscope image of the hydrogel coating prepared in example 4 of the present invention on the surface of the staphylococcus aureus bacteria liquid co-incubation coating.
FIG. 3 is a field emission electron microscope image of the hydrogel coating prepared in example 4 of the present invention soaked in hyaluronidase solution.
FIG. 4 is a field emission electron microscope image of a hydrogel coating prepared in example 4 of the present invention before and after bending 150 times.
FIG. 5 is a water contact angle image of a 3D printed large intestine rubbing 400 times with the hydrogel coating prepared in example 4 of the present invention.
FIG. 6 is an image of a hydrogel coating prepared in example 4 of the present invention soaked in deionized water for 60 days.
Detailed Description
The following detailed description of the embodiments of the present invention is provided in conjunction with the accompanying drawings, but the scope of the invention is not limited thereto.
Unless otherwise specified, the raw materials used in the examples of the present invention are all commercially available or available to those skilled in the art; unless otherwise specified, the methods used in the examples of the present invention are all those known to those skilled in the art.
General examples
A preparation method of high-strength degradable antibacterial hydrogel comprises the following preparation steps:
1) grafting methacrylamide on hyaluronic acid, wherein the molecular weight of the hyaluronic acid is less than 5000, and the grafting rate of the hyaluronic acid is 65-75%;
2) treating the polymer substrate with oxygen plasma for 0.5-5 min, and then soaking the polymer substrate under a hydrophobic initiator for 5-240 min, wherein the polymer substrate is PDMS, and the hydrophobic initiator is benzophenone methanol or isopropanol solution;
3) dissolving a zwitterionic monomer, hyaluronic acid, N, N '-Methylene Bisacrylamide (MBA) and alpha-ketoglutaric acid in deionized water, and then uniformly stirring to form a mixed solution, wherein the zwitterionic monomer comprises one or two of sulfobetaine methyl methacrylate and carboxylic betaine methyl methacrylate, the concentration of the zwitterionic monomer is 0.1-4.0 mol/L, the concentration of the hyaluronic acid is 0.4-0.8 mol% of that of the zwitterionic monomer, the concentration of the N, N' -methylene bisacrylamide is 0.01-0.20 mol% of that of the zwitterionic monomer, and the dosage of an initiator is 0.5-4.0 mol% of that of the zwitterionic monomer;
4) introducing the mixed solution into nitrogen or inert gas for deoxidizing, and removing bubbles in the mixed solution by ultrasound to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for 0-60 min;
6) and irradiating the polymer substrate subjected to standing for 3-8 hours by ultraviolet light of 350-380 nm of a glass mold until the reaction is finished, ultrasonically cleaning for 0.5-2 hours to remove the non-crosslinked hydrogel coating, and obtaining the uniform bacterial-responsive antifouling zwitter-ion hydrogel coating after the reaction is finished.
Examples 1 to 9
A preparation method of high-strength degradable antibacterial hydrogel comprises the following preparation steps:
1) grafting methacrylamide on hyaluronic acid, wherein the molecular weight of the hyaluronic acid is less than 5000, and the grafting rate of the hyaluronic acid is 70.6%;
2) treating the polymer substrate with oxygen plasma for 2min, and then soaking the polymer substrate in a hydrophobic initiator for 5-240 min, wherein the polymer substrate is PDMS, and the hydrophobic initiator is a benzophenone methanol solution;
3) dissolving a zwitterionic monomer, hyaluronic acid, N, N '-Methylene Bisacrylamide (MBA) and alpha-ketoglutaric acid in deionized water, and then uniformly stirring to form a mixed solution, wherein the zwitterionic monomer is sulfobetaine methyl methacrylate with the concentration of 0.1-4.0 mol/L, the concentration of hyaluronic acid is 0.4-0.8 mol% relative to the zwitterionic monomer, the concentration of N, N' -methylene bisacrylamide is 0.01-0.20 mol% relative to the zwitterionic monomer, and the dosage of an initiator is 0.5-4.0 mol% relative to the zwitterionic monomer;
4) introducing the mixed solution into nitrogen to remove oxygen, and removing bubbles in the mixed solution by ultrasonic to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for 0-60 min;
6) and (3) irradiating the polymer substrate subjected to standing for 6h by using 365nm ultraviolet light of a glass mold until the reaction is finished, ultrasonically cleaning for 1h to remove the non-crosslinked hydrogel coating, and obtaining the uniform amphoteric ion hydrogel coating with bacterial responsiveness and antifouling property after the reaction is finished.
Wherein the formulations of step 3) in examples 1 to 9 are shown in table 1 below, wherein MBA and hyaluronic acid are used in relative mole percentages (mol%) relative to the sulfobetaine methyl methacrylate.
Table 1 step 3) ingredient table.
Upper connection meter
In addition, specific preparation parameters of steps 2, 5 and 6) of examples 1 to 9 are shown in table 2 below.
Table 2 specific preparation parameters.
The preparation is carried out according to the ingredients in table 1 and the preparation parameters in table 2, and the performance of the hydrogel coating prepared in the embodiments 1 to 9 is tested after the preparation is finished. The performance test comprises the following aspects:
testing the binding force performance: cutting the prepared polymer sample containing the hydrogel coating into a round sample (the thickness is 3mm) with the diameter of 25mm, and testing the change condition of the torque of the sample along with time under the condition of constant normal force by adopting an advanced extended rheometer; the friction coefficient is calculated by the following formula, wherein W is the normal force, the rotation angular velocity ω is 0.5rad/s, T is the torque (unit: mN · m) measured experimentally, and R is 12.5 mm;
(2) and (3) testing antibacterial performance: placing the sheet sample of which the hydrogel coating is soaked for 10min by using 75% alcohol and PBS buffer solution into a 12-hole plate, adding 3mL of staphylococcus aureus bacterial liquid into each hole, controlling the Optical Density (OD) of the bacterial liquid to be 0.05, then placing the 12-hole plate into a shaking table, and co-culturing the sample and the bacterial liquid at 37 ℃ and at the rotating speed of 120rpm for 12 h. Then dyeing the strain with a coloring agent for 15min under a dark condition, washing the strain with phosphate buffer solution PBS, observing the adhesion condition of bacteria with an inverted fluorescence microscope, and observing the surface appearance with a field emission electron microscope after sterilization;
(3) and (3) testing the degradation performance: the hydrogel was placed in PBS buffer to completely swell, then the hydrogel coated block sample was removed and placed in a twelve well plate, 1mg/L hyaluronidase in PBS was added, and placed in a 37 ℃ shaker. Changing every day, and recording the surface appearance change by using a field emission electron microscope;
(4) and (3) testing the bending resistance: performing bending experiments on PDMS with hydrogel coatings for 150 times, and observing the surface appearance before and after bending by using a field emission electron microscope;
(5) and (3) testing the friction resistance: placing a 3D printed large intestine loaded with a 50g weight on the hydrogel coating, and pulling the large intestine to slide under constant force, wherein the friction times are 400 times; measuring the static contact angle theta of the surface of the coating before and after friction by using an optical contact angle measuring instrument, wherein the measurement result is the average value of the left contact angle and the right contact angle;
(6) and (3) stability testing: the hydrogel coating is soaked in deionized water for 60 days at normal temperature, and the change of the surface and the deionized water is observed and photographed and recorded every day after changing the water.
The coefficient of friction of the hydrophobic initiator for different soak times for the polymer substrates prepared in example 1 is shown in table 3. When the soaking time is gradually increased, the mechanical property of the friction coefficient sample of the hydrogel coating is firstly improved and then reduced, and when the soaking time is 5min, the friction coefficient reaches the lowest value of 0.05.
Table 3 coefficient of friction of hydrogel coatings prepared in example 1 in hydrophobic initiators for different soaking times.
SoakingTime
Blank space
5min
30min
120min
240min
Coefficient of friction
0.68
0.05
0.46
0.08
0.12
The friction coefficient of the hydrogel coating of the hydrogel pre-polymerized liquid prepared in example 2 at different standing times is shown in table 4, the friction coefficient of the hydrogel coating sample decreases and then increases with the increase of the standing time, and the friction coefficient reaches the lowest value of 0.05 when the standing time is 0.5 h.
Table 4 coefficient of friction of the hydrogel coating obtained in example 2 in the prepolymerization solution for different standing times.
Standing time
Blank space
0h
0.5h
1h
Coefficient of friction
0.68
0.58
0.05
0.4
The coefficient of friction of the hydrogel coatings prepared in examples 3, 4, 5, and 6 with different SBMA contents is shown in table 5, where the coefficient of friction decreased first and then increased as the SBMA content increased, and the coefficient of friction of the hydrogel coating tended to increase overall, with the SBMA concentration being the lowest at 0.5M.
Table 5 friction coefficients for hydrogel coatings of different SBMA contents prepared in examples 3 to 6.
SBMA concentration
Blank space
0.1M
0.5M
2M
4M
Coefficient of friction
0.68
0.07
0.05
0.16
0.2
The coefficient of friction of the hydrogel coatings prepared in examples 7, 8 and 9 with different MBA contents is shown in Table 6, and the coefficient of friction of the gel coating decreases first and then increases when the MBA content increases, and is at least 0.05 when the MBA content is 0.1 mol% relative to the SBMA.
Table 6 friction coefficients for hydrogel coatings of different MBA contents prepared in examples 7 to 9.
Concentration of MBA
Blank space
0.02mol％
0.1mol％
0.2mol％
Coefficient of friction
0.68
0.38
0.05
0.49
Example 4 Staphylococcus aureus produced was attached to (A)1～A3) Hydrogel coated PDMS and (B)1～B3) Fluorescence microscopy images on PDMS. As can be seen from fig. 1, the hydrogel coating prepared has a good antibacterial effect compared to PDMS.
The image of the field emission electron microscope of the surface of the hydrogel coating after the co-incubation of the staphylococcus aureus liquid prepared in example 4 is shown in fig. 2, and it can be seen from the image that the surface of the hydrogel coating has a layered structure in 4 th and 5 th days, and the coating is degraded and peeled off in the process.
Fig. 3 shows the degraded field emission electron microscope image of the hydrogel coating prepared in example 4, and it can be seen that the hydrogel coating has a layered structure on days 4 and 5, and the coating is degraded and peeled off in the process.
The image of the hydrogel coating prepared in example 4 obtained by bending 150 times by field emission electron microscope is shown in fig. 4, and no significant number of cracks are observed on the surface of the sample before and after bending.
The water contact angle image of the hydrogel coating prepared in example 4 after being rubbed 400 times is shown in fig. 5, and the static water contact angle before and after the rubbing is slightly increased compared with the static water contact angle before the rubbing, and the surface of the coating still keeps hydrophilic.
The image of the hydrogel coating prepared in example 4 after soaking in deionized water for 60 days is shown in fig. 6, and the soaked coating has no obvious change.
Example 10
A preparation method of high-strength degradable antibacterial hydrogel comprises the following preparation steps:
1) grafting methacrylamide on hyaluronic acid, wherein the molecular weight of the hyaluronic acid is less than 5000, and the grafting rate of the hyaluronic acid is 65%;
2) treating the polymer substrate with oxygen plasma for 2min, and soaking for 5min under a hydrophobic initiator, wherein the polymer substrate is PDMS, and the hydrophobic initiator is benzophenone methanol;
3) dissolving a zwitterionic monomer, hyaluronic acid, N' -Methylene Bisacrylamide (MBA) and alpha-ketoglutaric acid in deionized water, and uniformly stirring to form a mixed solution, wherein the zwitterionic monomer is the mixture of sulfobetaine methyl methacrylate and carboxylic betaine methyl methacrylate according to the concentration of 1: 1 and the total concentration of the two is 4.0mol/L, the concentration of hyaluronic acid is 0.4 mol% relative to the zwitterionic monomer, the concentration of N, N' -methylene-bisacrylamide is 0.01 mol% relative to the zwitterionic monomer, and the amount of the initiator is 2 mol% relative to the zwitterionic monomer;
4) introducing the mixed solution into nitrogen to remove oxygen, and removing bubbles in the mixed solution by ultrasonic to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for 30 min;
6) and (3) irradiating the polymer substrate subjected to standing for 3h by using ultraviolet light of 380nm in a glass mold until the reaction is finished, ultrasonically cleaning for 2h to remove the non-crosslinked hydrogel coating, and obtaining the uniform amphoteric ion hydrogel coating with bacterial responsiveness and fouling resistance after the reaction is finished.
Example 11
A preparation method of high-strength degradable antibacterial hydrogel comprises the following preparation steps:
1) grafting methacrylamide on hyaluronic acid, wherein the molecular weight of the hyaluronic acid is less than 5000, and the grafting rate of the hyaluronic acid is 75%;
2) treating the polymer substrate with oxygen plasma for 0.5min, and soaking the polymer substrate in a hydrophobic initiator for 30min, wherein the polymer substrate is PDMS, and the hydrophobic initiator is isopropanol solution;
3) dissolving a zwitterionic monomer, hyaluronic acid, N, N '-Methylene Bisacrylamide (MBA) and alpha-ketoglutaric acid in deionized water, and uniformly stirring to form a mixed solution, wherein the zwitterionic monomer is carboxylic acid betaine methyl methacrylate and the concentration of the zwitterionic monomer is 0.1mol/L, the concentration of the hyaluronic acid is 0.8 mol% relative to the zwitterionic monomer, the concentration of the N, N' -methylene bisacrylamide is 0.20 mol% relative to the zwitterionic monomer, and the dosage of an initiator is 0.5 mol% relative to the zwitterionic monomer;
4) introducing the mixed solution into helium gas for deoxidizing, and removing bubbles in the mixed solution through ultrasound to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for 60 min;
6) and (3) irradiating the polymer substrate subjected to standing for 3 hours by ultraviolet light at 350nm of a glass mold until the reaction is finished, ultrasonically cleaning for 0.5 hour to remove the non-crosslinked hydrogel coating, and obtaining the uniform bacterial-responsive antifouling zwitter-ion hydrogel coating after the reaction is finished.
Example 12
A preparation method of high-strength degradable antibacterial hydrogel comprises the following preparation steps:
1) grafting methacrylamide on hyaluronic acid, wherein the molecular weight of the hyaluronic acid is less than 5000, and the grafting rate of the hyaluronic acid is 70%;
2) treating the polymer substrate with oxygen plasma for 5min, and soaking the polymer substrate in a hydrophobic initiator for 5min, wherein the polymer substrate is PDMS, and the hydrophobic initiator is isopropanol solution;
3) dissolving a zwitterionic monomer, hyaluronic acid, N, N '-Methylene Bisacrylamide (MBA) and alpha-ketoglutaric acid in deionized water, and uniformly stirring to form a mixed solution, wherein the zwitterionic monomer is sulfobetaine methyl methacrylate and has a concentration of 0.2mol/L, the concentration of hyaluronic acid is 0.6 mol% relative to the zwitterionic monomer, the concentration of N, N' -methylene bisacrylamide is 0.1 mol% relative to the zwitterionic monomer, and the amount of an initiator is 4.0 mol% relative to the zwitterionic monomer;
4) introducing the mixed solution into nitrogen to remove oxygen, and removing bubbles in the mixed solution by ultrasonic to obtain a pre-solution;
5) uniformly dripping the pre-solution on the surface of a polymer substrate, and standing for 0-60 min;
6) and (3) irradiating the polymer substrate subjected to standing for 3h by ultraviolet light at 350nm of a glass mold until the reaction is finished, ultrasonically cleaning for 2h to remove the non-crosslinked hydrogel coating, and obtaining the uniform amphoteric ion hydrogel coating with bacterial responsiveness and fouling resistance after the reaction is finished.
The preparation method is simple, efficient, environment-friendly and environment-friendly as shown by a large number of detection results; the hydrogel coating is prepared from zwitterions, MBA and hyaluronic acid, the elastic network of the hydrogel is covalently grafted when the polymer substrate is soaked in a hydrophobic initiator, and the hydrogel coating and the polymer substrate form interfacial interpenetrating firm combination; can be stored in deionized water for a long time; the invention has excellent hydrophilicity, bending resistance and friction resistance, thus having wide application prospect in the field of biomedical surface materials, in particular to the aspect of medical catheter surface coatings and the like.