A hydrogel coating for the functionalization of various substrate interfaces and methods of making and using the same

Abstract

The application discloses a hydrogel coating for interface functionalization of various substrates and a preparation method and application thereof, and relates to the technical field of biomedical materials. The method comprises the following steps: pretreating a medical substrate surface; uniformly dispersing an adhesion unit, a monomer capable of bonding a functional group of the substrate surface, a first cross-linking agent and a first initiator in an aqueous solvent to obtain a primer layer precursor solution; uniformly dispersing a functional monomer, a second initiator and a second cross-linking agent in an aqueous solvent to obtain a functional layer precursor solution; and coating the primer layer precursor solution and the functional layer precursor solution on the pretreated substrate surface in sequence to obtain the hydrogel coating for interface functionalization of the substrate. The application effectively solves the problems of complex manufacturing process, irreversible working mode and single function of a traditional coating.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a hydrogel coating for interface functionalization of various substrates and a preparation method and application thereof. BACKGROUND

[0002] A three-dimensional network flexible hydrogel coating with high water content can be coated on various substrates with any shape and is widely used in medical materials and equipment. However, the current manufacturing process is generally complex, the working mode of the coating is irreversible, the function is single, and the research on the flexible electronic field for health monitoring is less. By adjusting the composition and structure of the material, the adhesion and functionalization of the substrate can be achieved, which has wide application and development potential.

[0003] However, the existing hydrogel coating is generally single-function, usually specially designed and prepared for specific application scenarios, and the whole preparation process is complicated, the production cost is high, and it is sensitive to solvent selection, which is difficult to popularize on a large scale. The existence of various problems hinders the further practical application of the hydrogel coating. In order to solve these problems, a new type of hydrogel coating needs to be developed, which should have the characteristics of strong anti-swelling ability, simplified production process, low cost, universality, simple preparation raw materials, stable adhesion performance, multifunctional and recyclable. SUMMARY

[0004] In view of the problems in the above background art, the present application aims to solve the technical problems that the existing hydrogel coating preparation process is complex and it is difficult to achieve strong adhesion to the substrate and multifunctional. The present application provides a hydrogel coating for interface functionalization of various substrates and a preparation method and application thereof. The present application uses a hydrogel primer layer with adhesion to bridge the substrate, and in-situ prepares a hydrogel functional layer crosslinked by a disulfide bond-containing crosslinking agent on the surface of the primer layer, to achieve the purpose of adhesion and function of the coating. In the application process, the adhesion unit in the primer layer plays a role, so that the adhesion layer is firmly combined with the surface of various medical substrates. Due to the presence of disulfide bond, the functional layer can be degraded under the action of some reducing agents. When the functional layer is completely degraded, the adhesion layer is exposed, and new functional layer can be in-situ polymerized on the surface of the adhesion layer to make the two-sided heterogeneous hydrogel coating play a new role. The overall thickness of the two-sided heterogeneous hydrogel coating in the present application is controllable, and it has reliable biological safety, which effectively solves the problems of complex manufacturing process and irreversible working mode of traditional coating, and single function.

[0005] The first object of the present application is to provide a preparation method of a hydrogel coating for interface functionalization of various substrates, comprising the following steps:

[0006] pretreating the surface of the medical substrate;

[0007] The adhesion unit, the monomer capable of bonding the functional groups of the substrate surface, and the first cross-linking agent and the first initiator are uniformly dispersed in the aqueous solvent to obtain a primer layer precursor solution;

[0008] The functional monomer, the second initiator, and the second cross-linking agent are uniformly dispersed in the aqueous solvent to obtain a functional layer precursor solution.

[0009] The primer layer precursor solution and the functional layer precursor solution are sequentially coated on the surface of the pretreated substrate to obtain a substrate interface functionalized hydrogel coating.

[0010] Preferably, in the primer layer precursor solution, the concentration of the adhesion unit is 0.1wt%-0.5wt%, the concentration of the monomer capable of bonding the functional groups of the substrate surface is 0.5wt%-15wt%, and the concentration of the cross-linking agent is 0.001wt%-0.05wt% and the concentration of the first initiator is 0.001wt%-0.05wt%.

[0011] Preferably, the adhesion unit comprises one or more of tannic acid, dopamine, protocatechuic acid, gallic acid, and tea polyphenols.

[0012] The monomer capable of bonding the functional groups of the substrate surface comprises one or more of acrylic acid, methacrylic acid, hydroxyethyl methacrylate, acrylic acid, and ethyl acrylate.

[0013] The first cross-linking agent is one or more of N-hydroxymethyl acrylamide, diacetone acrylamide, N,N-methylenebisacrylamide, and di-tert-butyl peroxyisopropylbenzene.

[0014] The first initiator is one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, and 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0015] Preferably, in the functional layer precursor solution, the concentration of the functional monomer is 0.1wt%-1.5wt%, the concentration of the second initiator is 0.01wt%-0.15wt%, and the concentration of the second cross-linking agent is 0.001wt%-0.05wt%.

[0016] Preferably, the functional monomer comprises sulfobetaine or N-isopropyl acrylamide.

[0017] The second initiator is one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, and 2-hydroxy-2-methyl-1-phenyl-1-propanone.

[0018] The second cross-linking agent comprises one or more of N,N'-cystamine bis(acrylamide), azido-bis-sulfide-ethyl, 3,3-dithiodipropionic acid bis(N-hydroxysuccinimidyl ester), dimercaptoacrylate.

[0019] Preferably, in the process of sequentially coating the primer layer precursor solution and the functional layer precursor solution on the pretreated substrate surface, the primer layer precursor solution is coated on the pretreated substrate surface, and after polymerization and cross-linking, a hydrogel primer layer is obtained.

[0020] Then, the functional layer precursor solution is coated on the surface of the hydrogel primer layer, and after polymerization and cross-linking, a hydrogel functional layer is obtained.

[0021] The hydrogel primer layer prepared on the substrate surface and the hydrogel functional layer on the hydrogel primer layer are the hydrogel coating for functionalization of the substrate interface.

[0022] Preferably, the method further comprises: degrading the hydrogel functional layer in the hydrogel coating for functionalization of the substrate interface by cleaving the cross-linking agent to expose the hydrogel primer layer, and then preparing another hydrogel functional layer on the exposed hydrogel primer layer.

[0023] Preferably, the cleaving cross-linking agent comprises one or more of dithiothreitol, 2-mercaptoethanol, mercaptoacetic acid, trimethylphosphine platinum chloride, thiol oxidase, protein disulfide isomerase, glutathione peroxidase, glutathione reductase, thiol reductase, perchloric acid, sodium iodate, hydrogen peroxide, sodium chromate, perchloric acid, potassium permanganate.

[0024] The second object of the present application is to provide a hydrogel coating for functionalization of a substrate interface.

[0025] The third object of the present application is to provide an application of the hydrogel coating for functionalization of a substrate interface in surface functionalization of a substrate.

[0026] Compared with the prior art, the present application has the following beneficial effects:

[0027] The present application provides a hydrogel coating for functionalization of a substrate interface, a preparation method and an application thereof. The method for preparing a two-sided anisotropic hydrogel coating has good adhesion, realizes close combination with various substrates, and effectively bridges the substrate and the functional layer. The overall preparation process of the coating is simplified, the cost is low, and the application can be widely promoted; the two-sided anisotropic hydrogel coating prepared by the present application has high universality. This is because the present application realizes the repeated disassembly of the functional layer by the double-layer double-sided design of the primer layer and the functional layer, and realizes the multifunctional and multi-scenario application by the combination and cleavage of the disulfide bond in the functional layer under the action of a specific reagent.

[0028] The hydrogel coating provided by the present application has good biocompatibility due to the characteristics of the hydrogel material itself. The hydrogel has a high water content and soft elasticity similar to biological tissues, and can be well compatible with surrounding tissues and cells. The surface properties and chemical composition of the hydrogel coating can be adjusted to further improve its biocompatibility and reduce adverse reactions on cells and tissues.

[0029] The present application benefits from the presence of the adhesive layer, which makes the overall coating adapt to the complex surface shape of various substrates, and does not peel off from the substrate during use to fail, while the disulfide bond in the functional layer can be cleaved under the action of a reducing agent to achieve the overall deconstruction and disassembly of the functional layer. After cleaning the functional layer, the functional layer can be recycled and constructed on the surface of the adhesive layer. This strategy avoids repeated pretreatment of the substrate, and the user does not need to consider the adhesion to the substrate while achieving the target function. Such a strategy endows the substrate with a reversible and diverse functional surface without changing the original mechanical properties and structure of the substrate. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 Preparation and function realization diagram of two-sided heterogeneous hydrogel coating;

[0031] Figure 2 Scanning electron microscope image of the surface micro-morphology of the two-sided heterogeneous hydrogel coating;

[0032] Figure 3 Biocompatibility of the two-sided heterogeneous hydrogel coating;

[0033] Figure 4 Two-sided heterogeneous hydrogel coating for antibacterial adhesion;

[0034] Figure 5 Two-sided heterogeneous hydrogel coating for nanometer friction generator sensing;

[0035] Figure 6 Water contact angle diagram of different surfaces. DETAILED DESCRIPTION

[0036] In order for those skilled in the art to better understand the technical solutions of the present application and implement them, the present application will be further described below in conjunction with specific embodiments and drawings, but the embodiments are not limiting to the present application.

[0037] The present application aims to solve the technical problems of the existing hydrogel coating preparation process, which is relatively complex, and it is difficult to consider strong adhesion to the substrate and realize multi-function, and provides a two-sided heterogeneous hydrogel coating preparation method suitable for the interface functionalization of various substrates.

[0038] The present application provides a hydrogel coating preparation method for the interface functionalization of various substrates, comprising the following steps:

[0039] pretreating the surface of the medical substrate;

[0040] dispersing the adhesion unit, the monomer capable of bonding the functional group of the substrate surface, and the first cross-linking agent and the first initiator in the aqueous solvent to obtain a primer layer precursor solution; wherein the monomer capable of bonding the functional group of the substrate surface comprises one or more of acrylic acid, methacrylic acid, hydroxyethyl methacrylate, acrylic acid, and ethyl acrylate;

[0041] dispersing the functional monomer, the second initiator, and the second cross-linking agent in the aqueous solvent to obtain a functional layer precursor solution; wherein the functional monomer comprises one or more of sulfobetaine, N-isopropyl acrylamide, hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), N-vinyl pyrrolidone (NVP), N,N-dimethyl acrylamide (DMA), methacrylic acid (MMA), butyl methacrylate (BMA), and acrylamide (AM);

[0042] coating the primer layer precursor solution and the functional layer precursor solution on the pretreated substrate surface in sequence to obtain the hydrogel coating layer for functionalizing the interface of the substrate.

[0043] In the process of coating the primer layer precursor solution and the functional layer precursor solution on the pretreated substrate surface in sequence, the primer layer precursor solution is coated on the pretreated substrate surface, and after polymerization and cross-linking, a hydrogel primer layer is obtained; then the functional layer precursor solution is coated on the surface of the hydrogel primer layer, and after polymerization and cross-linking, a hydrogel functional layer is obtained; the hydrogel primer layer prepared on the substrate surface and the hydrogel functional layer on the hydrogel primer layer are the hydrogel coating layer for functionalizing the interface of the substrate.

[0044] pretreating the surface of the medical substrate, specifically cleaning the surface of the substrate and drying it with nitrogen for standby, and performing surface plasma activation treatment on the relatively inert silica gel catheter and other substrates to change their wettability.

[0045] In the primer layer precursor solution, the concentration of the adhesion unit is 0.1wt%-0.5wt%, the concentration of the monomer capable of bonding the functional group of the substrate surface is 0.5wt%-15wt%, and the concentration of the cross-linking agent is 0.001wt%-0.05wt% and the concentration of the first initiator is 0.001wt%-0.05wt%.

[0046] The adhesion unit comprises one or more of tannic acid, dopamine, protocatechuic acid, gallic acid, and tea polyphenol;

[0047] The first cross-linking agent is one or more of N-hydroxymethyl acrylamide, diacetone acrylamide, N,N'-methylenebisacrylamide, di-tert-butyl peroxyisopropylbenzene;

[0048] The first initiator is one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone;

[0049] In the functional layer precursor solution, the concentration of the functional monomer is 0.1wt% to 1.5wt%, the concentration of the second initiator is 0.01wt% to 0.15wt%, and the concentration of the second cross-linking agent is 0.001wt% to 0.05wt%.

[0050] The second initiator is one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone;

[0051] The second cross-linking agent includes one or more of N,N'-cystamine bis(acrylamide), azido-bis-sulfur-ethyl, 3,3-dithiodipropionic acid di(N-hydroxy succinimidyl ester), dimercapto acrylate.

[0052] According to the present application, the water gel functional layer in the water gel coating layer is degraded by cleaving the cross-linking agent to expose the water gel primer layer, and then other water gel functional layers are prepared on the exposed water gel primer layer.

[0053] The cleaving cross-linking agent includes one or more of dithiothreitol, 2-mercaptoethanol, mercaptoacetic acid, trimethylphosphine platinum chloride, thiol oxidase, protein disulfide isomerase, glutathione peroxidase, glutathione reductase, thiol reductase, perchloric acid, sodium iodate, hydrogen peroxide, sodium chromate, perchloric acid, potassium permanganate.

[0054] In an embodiment, a two-sided heterogeneous water gel coating layer preparation method suitable for various substrate interface functionalization adopts a two-sided heterogeneous mode, uses an adhesion layer to bridge the substrate, and separately prepares water gel functional layers. A reducible degradable cross-linking agent is introduced to form detachable functional layers, and the functional layers can be replaced as needed, see Figure 1 The specific steps include:

[0055] 1) Clean the surface of the polymer, metal or inorganic non-metal medical device substrate and dry it with nitrogen for standby. For more inert silicone catheters and other substrates, perform surface plasma activation treatment to change their wettability;

[0056] 2) Formulate a hydrogel precursor solution containing adhesion units, monomers with functional groups that can bond to the surface of the substrate, add a first crosslinking agent and a first initiator, as an adhesion layer precursor primer for use;

[0057] The first crosslinking agent is one or more of N-methylol acrylamide, diacetone acrylamide, N,N-methylenebisacrylamide, di-tert-butyl peroxyisopropylbenzene;

[0058] The first initiator is one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone;

[0059] 3) Formulate a hydrogel functional layer precursor solution containing functional monomers including sulfobetaine, N-isopropyl acrylamide, hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), N-vinylpyrrolidone (NVP), N,N-dimethyl acrylamide (DMA), methacrylic acid (MMA), butyl methacrylate (BMA), or acrylamide (AM); a second initiator, a degradable disulfide-containing crosslinking agent (second crosslinking agent) for use;

[0060] 4) The hydrogel primer prepared in step 2) is uniformly attached to the cleaned surface of the substrate obtained in step 1) by spraying, scraping, dropping, or soaking, and the entire surface is irradiated with ultraviolet light for 10 minutes to induce polymerization and crosslinking of the free radical-initiated monomers in the surface adhesion layer primer, thereby shaping and constructing a hydrogel primer layer on the surface of the substrate;

[0061] 5) The hydrogel functional layer precursor solution prepared in 3) is attached to the primer layer prepared in step 4) by spraying, scraping, dropping, or soaking, and the entire surface is subjected to heating, blue light, ultraviolet light, X-ray, electron beam irradiation, or ultrasonic treatment to induce polymerization and crosslinking of the free radical-initiated monomers in the functional layer precursor solution, resulting in a detachable hydrogel functional layer containing disulfide bonds (the detachable concept is equivalent to degradable);

[0062] 6) Further break the disulfide bonds by cleaving the disulfide bond-containing components of the cleavable crosslinking agent, achieve the overall degradation of the functional layer, clean the surface of the adhesion layer after degradation is complete, and further polymerize in situ on the surface, i.e., step 4) to achieve on-demand replacement of the functional layer.

[0063] The composition of the hydrogel adhesive layer precursor primer is as follows: the adhesive unit is one or more of tannic acid, dopamine, protocatechuic acid, gallic acid and tea polyphenols, the concentration is 0.1wt%-0.5wt%, the monomer with the function of bonding the surface functional groups of the substrate is one or more of acrylic acid, methacrylic acid, hydroxyethyl methacrylic acid ester, acrylic acid and ethyl acrylate, the concentration is 0.5wt%-15wt%, the concentration of the first initiator is 0.001wt%-0.05wt%, the concentration of the first crosslinking agent is 0.001wt%-0.05wt%, and the balance is ultrapure water.

[0064] The composition of the hydrogel functional layer precursor solution is as follows: the concentration of the functional monomer is 0.1wt%-1.5wt%, the concentration of the second initiator is 0.01wt%-0.15wt%, the concentration of the degradable disulfide bond-containing crosslinking agent is one or more of N,N'-cystamine bis(acrylamide), azido-bisulfide-ethyl, 3,3-dithiodipropionic acid di(N-hydroxy succinimide ester) and dimercapto acrylate, and the balance is ultrapure water.

[0065] The cleavage component of the disulfide bond contained in the cleavable crosslinking agent is one or more of dithiothreitol, 2-mercaptoethanol, mercaptoacetic acid, trimethylphosphine platinum chloride, thiol oxidase, protein disulfide isomerase, glutathione peroxidase, glutathione reductase, thiol reductase, perchloric acid, sodium iodate, hydrogen peroxide, sodium chromate, perchloric acid and potassium permanganate.

[0066] It should be noted that the hydrogel coating thickness of the present application is controllable, the adhesion is strong, and the function is reversible.

[0067] The second aspect of the present application provides a hydrogel coating for functionalization of a substrate interface.

[0068] The third aspect of the present application provides a hydrogel coating for functionalization of a substrate interface for application in the functionalization of a substrate surface.

[0069] It should be noted that the experimental methods used in the present application are conventional methods unless otherwise specified; and the reagents and materials used are commercially available unless otherwise specified.

[0070] Example 1

[0071] A method for preparing a hydrogel coating for functionalization of a substrate interface, as shown in Figure 1 The method comprises the following steps:

[0072] Firstly, tannic acid 0.1wt%, acrylic acid 0.5wt%, initiator ammonium persulfate 0.001wt%, crosslinking agent N-N-methylene double acrylamide 0.001wt% were weighed, and then mixed with ultrapure water, magnetically stirred until uniform, and reserved for use as primer layer precursor solution.

[0073] Then, functional monomer sulfobetaine 1.5wt%, initiator ammonium persulfate 0.01wt%, N, N'-cystamine bis(acrylamide) 0.05wt% were weighed, and then mixed with ultrapure water, magnetically stirred until uniform, and reserved for use as functional layer precursor solution.

[0074] The primer layer precursor solution and the functional layer precursor solution were coated and cured on the surface of the metal titanium sheet substrate in turn, a certain amount of precursor solution was taken with a brush, dropped on the surface of the substrate with a dropper, and then evenly coated with a scraper, and then cured with ultraviolet light for 10min to obtain a stain-resistant two-sided heterogeneous hydrogel coating.

[0075] The two-sided heterogeneous hydrogel coating was immersed in dithiothreitol to degrade the functional layer and expose the primer layer for standby use.

[0076] Example 2

[0077] Firstly, dopamine 0.1wt%, acrylic acid 0.5wt%, initiator lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate 0.001wt%, crosslinking agent diacetone acrylamide 0.001wt% were weighed, and then mixed with ultrapure water, magnetically stirred until uniform, and reserved for use as primer layer precursor solution.

[0078] Then, functional monomer sulfobetaine 1.5wt%, initiator 0.01wt%, N, N'-cystamine bis(acrylamide) 0.05wt% were weighed, and then mixed with ultrapure water, magnetically stirred until uniform, and reserved for use as functional layer precursor solution.

[0079] The primer layer precursor solution and the functional layer precursor solution were coated and cured on the surface of the metal titanium sheet substrate in turn to obtain a stain-resistant two-sided heterogeneous hydrogel coating.

[0080] The two-sided heterogeneous hydrogel coating was immersed in dithiothreitol to degrade the functional layer and expose the primer layer for standby use.

[0081] Example 3

[0082] Firstly, tannic acid 0.1wt%, acrylic acid 0.5wt%, initiator ammonium persulfate 0.001wt%, crosslinking agent N-hydroxymethyl acrylamide 0.001wt% were weighed, and then mixed with ultrapure water, magnetically stirred until uniform, and reserved for use as primer layer precursor solution.

[0083] The functional monomer sulfobetaine 1.5 wt%, initiator 0.01 wt%, N, N'-cystamine bis(acrylamide) 0.05 wt% are weighed again, mixed with ultrapure water, magnetically stirred until uniform, and reserved as a functional layer precursor solution.

[0084] The primer layer precursor solution and the functional layer precursor solution are coated and cured on the surface of the metal titanium sheet substrate in turn to obtain a stain-resistant two-sided heterogeneous hydrogel coating.

[0085] The two-sided heterogeneous hydrogel coating is immersed with 2-mercaptoethanol to degrade the functional layer and expose the primer layer for standby.

[0086] Example 4

[0087] The tannic acid 0.1 wt%, acrylic acid 0.5 wt%, initiator lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate 0.001 wt%, crosslinking agent bis-tert-butyl peroxyisopropylbenzene 0.001 wt% are weighed first, mixed with ultrapure water, magnetically stirred until uniform, and reserved as a primer layer precursor solution.

[0088] The functional monomer N-isopropyl acrylamide 1.5 wt%, initiator 0.01 wt%, N, N'-cystamine bis(acrylamide) 0.05 wt% are weighed again, mixed with ultrapure water, magnetically stirred until uniform, and reserved as a functional layer precursor solution. The primer layer precursor solution and the functional layer precursor solution are coated and cured on the surface of the metal titanium sheet substrate in turn to obtain a thermal response two-sided heterogeneous hydrogel coating.

[0089] The two-sided heterogeneous hydrogel coating is immersed with dithiothreitol to degrade the functional layer and expose the primer layer for standby.

[0090] Example 5

[0091] The tannic acid 0.1 wt%, acrylic acid 0.5 wt%, initiator 2,4,6-trimethylbenzoyl diphenyl phosphate 0.001 wt%, crosslinking agent bis-tert-butyl peroxyisopropylbenzene 0.001 wt% are weighed first, mixed with ultrapure water, magnetically stirred until uniform, and reserved as a primer layer precursor solution.

[0092] The functional monomer sulfobetaine 1.5 wt%, initiator 0.01 wt%, 3,3-dithiodipropionic acid di(N-hydroxy succinimide ester) 0.05 wt% are weighed again, mixed with ultrapure water, magnetically stirred until uniform, and reserved as a functional layer precursor solution. The primer layer precursor solution and the functional layer precursor solution are coated and cured on the surface of the metal titanium sheet substrate in turn to obtain a stain-resistant two-sided heterogeneous hydrogel coating.

[0093] The two-sided heterogeneous hydrogel coating is immersed with dithiothreitol to degrade the functional layer and expose the primer layer for standby.

[0094] To illustrate the relevant performance of the coating provided by the present application, it is described in conjunction with the accompanying drawings.

[0095] Figure 2 The surface micro-morphology scanning electron microscope image of the two-sided Janus hydrogel coating prepared according to Example 1 is well combined with the substrate, and the image shows that the coating surface is smooth and has good spreading effect. Among them, Figure 2 a The upper half is a TiNi substrate, and the lower half is a primer layer with a thickness of 9 μm; Figure 2 b is a schematic diagram of the primer layer after uniform coating, and it can be seen that the coating surface is smooth; Figure 2 c is a schematic diagram of the functional layer after uniform coating on the primer layer, and the spreading effect is good.

[0096] Figure 3 The biocompatibility of the two-sided Janus hydrogel coating prepared according to Example 2 is compared with the relative cell survival rate of the control group. The relative cell survival rate of the Ti sheet without hydrogel coating is slightly lower, while the Ti sheet with coating greatly improves the relative cell survival rate, close to the control group, indicating that the two-sided Janus hydrogel coating greatly improves the biocompatibility of the original substrate and can be safely used for applications in contact with biological tissues;

[0097] Figure 4 The two-sided Janus hydrogel coating prepared according to Example 3 is used for antibacterial adhesion. This figure shows the comparison of the antibacterial adhesion ability of two different materials Ti and the surface coated with two-sided Janus hydrogel to S. aureus and E. coli. For S. aureus, the bacterial count on the pure titanium surface is higher, close to 5 units, while the bacterial count on the surface of Ti Janus Hydrogel is significantly reduced, about 3 units. For E. coli, the bacterial count on the pure titanium surface is higher, higher than 4 units, while the bacterial count on the Ti surface coated with two-sided Janus hydrogel coating is significantly reduced, less than 3 units, effectively showing the advantages of two-sided Janus hydrogel coating in reducing common bacterial adhesion and improving surface antibacterial properties;

[0098] Figure 5 The two-sided Janus hydrogel coating prepared according to Example 4 is used for nanometer friction generator sensing. A back electrode of a nanometer friction generator with conductive function is constructed, and a certain short-circuit current is output.

[0099] Figure 6 The water contact angle diagram of different surfaces shows that the water contact angle of the Ti substrate is larger, while the water contact angle of the substrate coated with the adhesion layer is significantly reduced. The presence of the adhesion layer can help the functional layer to achieve good spreading, which is beneficial to the overall construction of the coating.

[0100] While embodiments of the application have been shown and described above, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and alterations can be made to the embodiments without departing from the principles and spirit of the application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for the preparation of hydrogel coatings for the functionalization of various substrate interfaces, characterized by, The method comprises the following steps: preprocessing the surface of a medical substrate; dispersing an adhesion unit, a monomer capable of bonding to the functional groups of the substrate surface, a first cross-linking agent and a first initiator in an aqueous solvent to obtain a primer layer precursor solution; wherein the monomer capable of bonding to the functional groups of the substrate surface comprises one or more of acrylic acid, methacrylic acid, hydroxyethyl methacrylate, and ethyl acrylate; dispersing a functional monomer, a second initiator, and a second cross-linking agent in an aqueous solvent to obtain a functional layer precursor solution; wherein the functional monomer comprises one or more of sulfobetaine, N-isopropyl acrylamide, hydroxyethyl methacrylate, hydroxypropyl methacrylate, N-vinyl pyrrolidone, N,N-dimethyl acrylamide, methacrylic acid, butyl methacrylate, and acrylamide; coating the primer layer precursor solution and the functional layer precursor solution on the surface of the pretreated substrate in sequence to obtain a substrate interface functionalized hydrogel coating; in the primer layer precursor solution, the concentration of the adhesion unit is 0.1wt%-0.5wt%, the concentration of the monomer capable of bonding to the functional groups of the substrate surface is 0.5wt%-15wt%, and the concentration of the first cross-linking agent is 0.001wt%-0.05wt% and the concentration of the first initiator is 0.001wt%-0.05wt%; the adhesion unit comprises one or more of tannic acid, dopamine, protocatechuic acid, gallic acid, and tea polyphenols; the first cross-linking agent comprises one or more of N-hydroxymethyl acrylamide, diacetone acrylamide, N,N-methylenebisacrylamide, and di-tert-butyl peroxyisopropylbenzene; the first initiator comprises one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, and 2-hydroxy-2-methyl-1-phenyl-1-propanone; in the functional layer precursor solution, the concentration of the functional monomer is 0.1wt%-1.5wt%, the concentration of the second initiator is 0.01wt%-0.15wt%, and the concentration of the second cross-linking agent is 0.001wt%-0.05wt%; the second initiator comprises one or more of ammonium persulfate, potassium persulfate, lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, and 2-hydroxy-2-methyl-1-phenyl-1-propanone; the second cross-linking agent comprises one or more of N,N'-cystamine bis(acrylamide), azido-bis-thio-ethyl, 3,3-dithiodipropionic acid di(N-hydroxysuccinimidyl ester), and dimercaptoethyl acrylate.

2. The method for preparing a hydrogel coating for the interface functionalization of various substrates according to claim 1, wherein in the process of coating the primer layer precursor solution and the functional layer precursor solution on the surface of the pretreated substrate in sequence, the primer layer precursor solution is coated on the surface of the pretreated substrate, and after polymerization and cross-linking, a hydrogel primer layer is obtained. A functional layer precursor solution is coated on the surface of the hydrogel primer layer, and after polymerization and crosslinking, a hydrogel functional layer is obtained; The hydrogel primer layer and the hydrogel functional layer on the hydrogel primer layer prepared on the surface of the substrate are the hydrogel coating for functionalization of the substrate interface.

3. The method of claim 2, further comprising: The hydrogel functional layer in the hydrogel coating for functionalization of the substrate interface is degraded by cleaving the crosslinking agent to expose the hydrogel primer layer, and other hydrogel functional layers are prepared on the exposed hydrogel primer layer.

4. The preparation method of the hydrogel coating for functionalization of a variety of substrate interfaces according to claim 3, wherein the cleaving crosslinking agent comprises one or more of dithiothreitol, 2-mercaptoethanol, mercaptoacetic acid, trimethylphosphine platinum chloride, thiol oxidase, protein disulfide isomerase, glutathione peroxidase, glutathione reductase, thiol reductase, perchloric acid, sodium iodate, hydrogen peroxide, sodium chromate, and potassium permanganate.

5. A substrate interface functionalized hydrogel coating prepared by the preparation method of any one of claims 1-4.

6. Application of the substrate interface functionalized hydrogel coating of claim 5 in functionalization of a substrate surface.

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