An anti-inflammatory and repair-promoting coating based on hydrogen sulfide donor, its preparation method and application

By fixing the hydrogen sulfide donor to the surface of biomedical materials through covalent bonds, the in-situ site release of hydrogen sulfide is achieved, and the problem of adverse reactions caused by existing biomedical materials in clinical applications is solved, and the biocompatibility and tissue repair effect of the material are significantly improved.

CN119055839BActive Publication Date: 2025-03-14SICHUAN UNIV
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Patent Information

Application Number
CN202411573215.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-11-06
Publication Date
2025-03-14
Estimated Expiration
2044-11-06

AI Technical Summary

Technical Problem

Existing biomedical materials are prone to induce inflammatory reactions, coagulation reactions and other adverse reactions in clinical applications, leading to high risk of implant failure and complications, and it is difficult to achieve sustained anti-inflammatory, anti-coagulant and tissue repair effects.

Method used

Through surface initiation technology, the hydrogen sulfide donor is fixed to the surface of the substrate through high-energy covalent bonds, realizing the in-situ site release of hydrogen sulfide gas transmitters, and building an anti-inflammatory and pro-repair coating.

Benefits of technology

The stability and biocompatibility of the coating are significantly improved, the biological properties of anti-inflammatory, anticoagulant and tissue repair are enhanced, the risk of postoperative complications is reduced, and the utilization rate of hydrogen sulfide at the lesion site is increased.

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Abstract

The present invention relates to the field of biomedical materials, and specifically provides an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, and a preparation method and application thereof. The coating contains a hydrogen sulfide donor, and can release hydrogen sulfide or its precursor spontaneously or under external stimulation. Hydrogen sulfide, as a reducing gas transmitter, has significant functions of anti-oxidation, scavenging reactive oxygen species, and regulating inflammation, and also exhibits excellent effects in anti-coagulation, cell protection, vasodilation, and promoting angiogenesis. The hydrogen sulfide-based anti-inflammatory and pro-repair coating of the present invention can impart excellent biological activity to biomedical materials, effectively solving the problems of insufficient biocompatibility and high risk of postoperative complications in the prior art. The technology has broad application prospects in the fields of medical implants, tissue engineering, and wound repair.
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Description

Technical Field

[0001] The invention relates to the field of biomedical materials, in particular to an anti-inflammatory and repair-promoting coating based on a hydrogen sulfide donor, and a preparation method and application thereof. Background Art

[0002] In the field of biomedical materials, how to effectively regulate the interaction between materials and organisms to achieve anti-inflammation, anti-coagulation, cell protection and promote tissue repair has always been a research focus. However, artificial implants or biomaterials are prone to induce inflammatory reactions, coagulation reactions and other adverse reactions in the body during clinical applications, which may not only lead to implant failure, but also cause a series of complications. Therefore, the development of new coating materials with multifunctional properties has become an important direction for biomedical material research.

[0003] As an endogenous gas signal molecule, hydrogen sulfide (H2S) has received extensive attention in medical research in recent years. Studies have shown that H2S plays an important regulatory role in a variety of physiological and pathological processes, including anti-oxidation, anti-inflammation, anti-coagulation, cell protection, vasodilation regulation, and tissue repair. In particular, in terms of anti-inflammation, H2S not only relies on the direct removal of reactive oxygen species (ROS) and reactive nitrogen species (RNS), but is more achieved by regulating the antioxidant mechanisms and systems in cells. These mechanisms include providing antioxidant protection at the cellular level by regulating the expression and activity of classic antioxidants such as glutathione (GSH) and thioredoxin (Trx). In addition, H2S can upregulate antioxidant systems such as the NF-E2-related factor2 (Nrf2) signaling pathway, thereby promoting the expression of a series of antioxidants and redox regulators in cells. This indirect signal transduction pathway enables H2S treatment to provide long-term and effective antioxidant protection, improve the survival and functional stability of cells in adverse environments, and effectively promote tissue regeneration and repair. In addition, H2S can play an anticoagulant role by inhibiting platelet activation and aggregation, which is of great significance for preventing thrombosis, especially in the application of vascular grafts and other cardiovascular implants.

[0004] For example, the patent with publication number CN115089773A discloses a bionic coating for vascular stents and a vascular stent and a preparation method thereof. The patent forms a coating by initiating a polymer cross-linking reaction with an initiator, but no covalent bond is formed between the coating and the substrate, resulting in poor adhesion. In addition, the functional molecules selected in the patent are used to adaptively generate signal factors (such as CO, H2S, TGF-β, etc.), including cystine, cysteine, CORM-3, diphenyl diselenide, diphenyl selenide, dimethyl selenide, L-cysteine, CORM-1, CORM-2, methyl sulfide, cystasene and proline. These molecules have no polymerization activity and cannot form a covalent bond with the coating during the coating construction process. Therefore, they are only fixed in the coating by physical embedding, and the stability is poor. Most of the functional molecules have been washed away by the blood flow before the corresponding signal factors are generated, resulting in low utilization and poor biological performance.

[0005] For example, the patent with publication number CN117398532A discloses an anticoagulant functional material based on the release of gas signal molecules and its preparation method. In this patent, although the gas signal molecule donor is combined with the polydopamine-polyethyleneimine coating through a covalent bond; however, the polydopamine-polyethyleneimine coating utilizes the good adhesion properties of polydopamine to attach to the surface of the base material, but its combination with the substrate is mostly physical adsorption or weak chemical force, so the bonding force between the coating and the substrate is limited. The coating is easily affected by external factors such as mechanical force and chemical environment changes during long-term use or in a complex physiological environment, resulting in a decrease in its stability and durability. In contrast, the present invention uses surface initiation technology to fix the hydrogen sulfide donor to the surface of the substrate through a high-energy covalent bond, which effectively improves the stability of the coating, and is conducive to the in-situ fixed-point release of hydrogen sulfide gas transmitters, maximizing the biological function. Summary of the invention

[0006] Technical problems solved by the present invention:

[0007] The technical problem to be solved by the present invention is how to construct an anti-inflammatory and repair-promoting coating that can release hydrogen sulfide in situ and at a fixed point, so as to improve the biocompatibility of biomedical materials, accelerate the tissue repair process, and significantly reduce the risk of postoperative complications.

[0008] The technical solution adopted by the present invention is:

[0009] Based on the aforementioned technical problems, the present invention aims to achieve multifunctional modification of the surface of biomaterials through innovative coating design, so that it can provide sustained anti-inflammatory, anticoagulant and tissue repair support in clinical applications.

[0010] Specifically,

[0011] First, the present invention provides an anti-inflammatory and pro-repair coating based on hydrogen sulfide donors.

[0012] The coating contains a hydrogen sulfide donor; the hydrogen sulfide donor releases hydrogen sulfide or a hydrogen sulfide precursor spontaneously or under external stimulation; and the coating is covalently attached to the surface of the substrate;

[0013] The aforementioned covalent connection is achieved through route one or route two:

[0014] Path 1: The initiator is fixed on the surface of the substrate or below by chemical means or physical adsorption; the initiator generates free radicals to initiate the polymerization of the hydrogen sulfide donor monomer;

[0015] Approach 2: The chemical bonds on the surface of the substrate are broken by irradiation, and the generated free radicals initiate the polymerization of the hydrogen sulfide donor monomer.

[0016] According to some preferred embodiments, the hydrogen sulfide donor monomer includes one or more carbon-carbon double bonds and one or more hydrogen sulfide donors; the carbon-carbon double bonds are derived from the carbon-carbon double bonds introduced into the hydrogen sulfide donors by chemical modification.

[0017] According to some preferred embodiments, the hydrogen sulfide donor monomer is obtained by chemical reaction of compound I and compound II:

[0018] Compound I is a compound containing a carbon-carbon double bond and a reactive group A; Compound II is a compound containing a hydrogen sulfide donor and a reactive group B;

[0019] The reactive group A includes at least one of carboxyl, acyl chloride, acid anhydride, epoxy, active ester, hydroxyl, amino, amino hydrochloride, carbon-carbon double bond, carbon-carbon triple bond, isocyanate, and thioisocyanate;

[0020] The conditions of the reactive group A and the reactive group B include at least one of the characteristics (1) to (4):

[0021] (1) When the reactive group A includes at least one of carboxyl, acyl chloride, acid anhydride, epoxy, active ester, isocyanate, and thioisocyanate, the reactive group B includes at least one of amino, hydroxyl, and thiol;

[0022] (2) When the reactive group A includes at least one of amino and hydroxylamino hydrochloride, the reactive group B includes at least one of carboxyl, acyl chloride, acid anhydride, epoxy, active ester, isocyanate, and thioisocyanate;

[0023] (3) When the reactive group A includes a carbon-carbon double bond, the reactive group B includes at least one of an amino group, an amino hydrochloride, and a thiol group;

[0024] (4) When the reactive group A includes a carbon-carbon triple bond, the reactive group B includes at least one of an amino group, an amino hydrochloride group, a thiol group, and an azide group.

[0025] According to some preferred embodiments, the hydrogen sulfide donor includes at least one of the following groups:

[0026] .

[0027] According to some preferred embodiments, the external stimulation comprises at least one of chemical stimulation, light stimulation, thermal stimulation and ultrasonic stimulation.

[0028] The chemical stimulation includes at least one of thiol compounds and reactive oxygen species; thiol compounds include cysteine ​​and glutathione; reactive oxygen species include hydrogen peroxide, superoxide anion, organic peroxide, lipid peroxide, and peroxynitrite.

[0029] Second, the present invention provides a method for preparing the anti-inflammatory and pro-repair coating based on hydrogen sulfide donor as mentioned above, comprising the following steps:

[0030] Through route one:

[0031] S1: pre-treating the substrate by immersing it in a solution containing an initiator to obtain a first treated body;

[0032] S2 the first treated body is immersed in a hydrogen sulfide donor monomer solution to obtain a second treated body;

[0033] S3 The second treated body is polymerized by initiating the surface polymerization of the initiator to obtain a material with a hydrogen sulfide donor coating;

[0034] Through route two:

[0035] S1: soaking the substrate in a solution containing a hydrogen sulfide donor monomer to obtain a first treated body;

[0036] S2 The first treated body is irradiated to initiate polymerization, thereby obtaining a material with a hydrogen sulfide donor coating.

[0037] Thirdly, the present invention provides an application of the aforementioned anti-inflammatory and pro-repair coating based on hydrogen sulfide donor in the preparation of biomedical materials.

[0038] The technical mechanism and beneficial effects adopted by the present invention are as follows:

[0039] (1) The present invention provides an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor. A bioactive coating containing a hydrogen sulfide donor is constructed on the surface of a biomedical material, which gives the substrate excellent biological properties such as anti-inflammatory, anti-coagulation, cell protection and promotion of tissue repair, effectively solving the problems of insufficient biocompatibility and high risk of postoperative complications of biomedical materials in the prior art.

[0040] (2) The present invention provides an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, which fixes the hydrogen sulfide donor to the surface of the substrate by covalent bonding, thereby achieving in-situ fixed-point release of hydrogen sulfide gas transmitter. This method effectively overcomes the problem of the traditional technology of blending and embedding the hydrogen sulfide donor in the coating, and avoids the phenomenon that hydrogen sulfide is released only after the donor diffuses into the surrounding healthy tissue, thereby improving the utilization rate of hydrogen sulfide in the lesion site and the therapeutic effect.

[0041] (3) The present invention utilizes cheap, clean and safe surface irradiation initiated polymerization technology to covalently bond a coating containing a hydrogen sulfide donor to the surface of a substrate. The method and technology used are safe, economical and conducive to large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is the S element peak diagram in the XPS surface element analysis of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD;

[0043] Figure 2 The hydrogen sulfide release behavior diagram of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD;

[0044] Figure 3 The results of subcutaneous implantation of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD in SD rats are shown (bar 200 μm);

[0045] Figure 4 The graphs are the platelet adhesion and activation results of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD;

[0046] Figure 5 The graphs show the results of endothelial cell adhesion and proliferation of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD (bar: 100 μm);

[0047] Figure 6 The graph shows the results of endothelial cell migration of PLLA, PLLA-PEG / RGD and PLLA-PEG-ABTA / RGD (bar: 100 μm). DETAILED DESCRIPTION

[0048] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0049] Example 1

[0050] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0051] (1) A hydrogen sulfide donor MA-PEG2000-ABTA containing a double bond was prepared by using a nucleophilic substitution reaction between an active ester of methacrylate polyethylene glycol (MA-PEG2000-NHS) and an active ester and an amino group in 4-aminothiobenzamide (ABTA). Specifically, an anhydrous tetrahydrofuran solution containing 10 wt% MA-PEG2000-NHS, 3 wt% triethylamine, and 3 wt% ABTA was prepared, and the mixture was stirred at room temperature for 24 h, precipitated in ether, and dried to obtain MA-PEG2000-ABTA.

[0052] (2) preparing a 5 wt% benzophenone / ethanol solution and passing nitrogen for 30 min; placing a polylactic acid (PLLA) substrate in the benzophenone / ethanol solution and irradiating it with ultraviolet light for 30 min to obtain a polylactic acid substrate PLLA-BP containing a photoinitiator;

[0053] (3) Prepare a monomer aqueous solution containing 10 wt% MA-PEG2000-ABTA and 0.5 wt% methacryloyl RGD polypeptide (MA-RGD), soak the PLLA-BP obtained in step (2) in the monomer aqueous solution, pass nitrogen for 30 min, and then irradiate with ultraviolet light for 30 min to obtain a material PLLA-PEG-ABTA / RGD with a hydrogen sulfide donor coating on the surface.

[0054] Example 2

[0055] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0056] (1) The polyurethane substrate is treated by plasma for 2 min to obtain a polyurethane substrate PU with surface hydrophilization treatment;

[0057] (2) MA-PEG2000-ABTA obtained in Example 1 is prepared into an aqueous solution with a concentration of 10 wt%; the surface-hydrophilized polyurethane substrate PU obtained in step (1) is placed in the aqueous solution of hydrogen sulfide donor monomer, vacuumed and then nitrogen-filled, cycled for 3 times, and sealed to obtain a second pre-treated body;

[0058] (3) The second treated body is placed under an electron beam for irradiation polymerization at a dose of 10 kGy, and then cleaned and dried with ethanol to obtain a material PU-PEG-ABTA having a hydrogen sulfide donor coating on the surface.

[0059] Example 3

[0060] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0061] (1) The polyurethane substrate (PU) was treated with plasma for 2 min and immersed in an acetone solution containing 10 wt% benzophenone (BP) for 10 min. After the monomer was dried, a matrix material PU-BP containing benzophenone on the surface was obtained;

[0062] (2) Prepare a monomer aqueous solution containing 10 wt% MA-PEG2000-ABTA and 0.5 wt% methacryloyl REDV polypeptide (MA-REDV), soak the PU-BP obtained in step (1) in the monomer solution, pass argon for 30 min, and then irradiate with ultraviolet light for 30 min to obtain a material PU-PEG-ABTA / REDV with a hydrogen sulfide donor coating on the surface.

[0063] Example 4

[0064] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0065] (1) Prepare 50 mL of anhydrous tetrahydrofuran solution containing 10 wt% 6-aminopyridine-3-carbosulfamide (APTC) and 10 wt% triethylamine, slowly dropwise add 10 mL of 50 wt% acrylic anhydride / anhydrous tetrahydrofuran solution to the solution, stir at room temperature for 24 hours, and separate and purify with a silica gel column to obtain acryloyl APTC (MA-APTC);

[0066] (2) ultrasonically cleaning the polypropylene substrate with ethanol and acetone three times in sequence to obtain a pretreated polypropylene substrate PP;

[0067] (3) preparing a 15% MA-APTC / N',N'-dimethylformamide solution; placing the polypropylene substrate PP obtained in step (2) in the MA-APTC / N',N'-dimethylformamide, passing argon gas for 30 minutes, and then placing it under X-ray irradiation polymerization at an irradiation dose of 50 kGy.

[0068] (4) The irradiated material obtained in step (3) is taken out, washed with N',N'-dimethylformamide three times, and then washed with ethanol three times. After drying, a material PP-APTC having a hydrogen sulfide donor coating on the surface is obtained.

[0069] Example 5

[0070] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0071] (1) The stainless steel substrate (SS) was polished with 800 to 4000 grit sandpaper and then immersed in a 10 wt% sodium hydroxide aqueous solution for 5 h at room temperature to obtain a hydroxylated stainless steel substrate SS-OH.

[0072] (2) preparing a solution containing 5wt% 3-(trimethoxysilyl)propyl-2-bromo-2-methylpropionate (CAS: 314021-97-1), 5wt% H2O, and 90wt% ethanol, and mixing them evenly. The SS-OH obtained in step (1) is immersed in the solution, reacted at room temperature for 1 hour, then washed with ethanol, and then cured at about 80°C for 1 hour to obtain a substrate SS-Br containing a surface initiator;

[0073] (3) Prepare a solution containing 0.5 g of MA-PEG2000-ABTA obtained in Example 1, 10 mg of copper bromide (CuBr), 15 μL of N,N,N,N,N-pentamethyldiethylenetriamine (PMEDTA) and 8 mL of ethanol, and pass argon for 30 min. Immerse the SS-Br obtained in step (2) in the solution and react at 45 °C for 12 h. Then take out the sample, wash it with ethanol and dry it to obtain the material SS-PEG-ABTA with a hydrogen sulfide donor coating on its surface.

[0074] Example 6

[0075] This embodiment provides a method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, comprising:

[0076] (1) An anhydrous dimethyl sulfoxide solution containing 3 wt% 4-(hydroxymethyl)phenylboronic acid pinacol ester, 20 wt% 1,4-phenylene diisocyanate, and 0.1 wt‰ di-n-butyltin dilaurate (DBTDL) was prepared and reacted at 60 °C for 12 h. After ether precipitation, the resulting product was separated and purified on a silica gel column to obtain a donor compound NCS-PeroxyTCM containing a thioisocyanate (NCS) functional group and a reactive oxygen species that releases hydrogen sulfide.

[0077] (2) preparing an anhydrous dimethyl sulfoxide solution containing 10 wt% N-(2-aminoethyl) methacrylamide hydrochloride, 5 wt% NCS-PeroxyTCM, and 10 wt% triethylamine, reacting at room temperature for 12 h, and separating and purifying with a silica gel column after ether precipitation to obtain hydrogen sulfide monomer MA-PeroxyTCM containing a carbon-carbon double bond;

[0078] (3) preparing a dimethyl sulfoxide solution containing 5 wt% MA-PeroxyTCM, 5 wt% polyethylene glycol methyl ether methacrylate (MA-PEG1000), 0.2 wt‰ copper bromide (CuBr2), 0.2 wt‰ tris(2-pyridylmethyl)amine (TPMA), and 5 wt% barium titanate nanoparticles (BaTiO3);

[0079] (4) The substrate (SS-Br) having an initiator coating on its surface obtained in Example 5 was immersed in the solution of step (3), degassed by freeze-thaw for three times, and then placed in an ultrasonic bath at 40 kHz and 70 W for 6 hours to initiate the polymerization reaction by ultrasound, thereby obtaining a material SS-PeroxyTCM / PEG having a hydrogen sulfide donor coating on its surface.

[0080] Comparative Example 1

[0081] This comparative example provides a method for preparing a comparative sample of a coating without a hydrogen sulfide donor, comprising:

[0082] (1) A 5 wt% benzophenone / ethanol solution was prepared and nitrogen was passed through for 30 min; a polylactic acid (PLLA) substrate was placed in the benzophenone / ethanol solution and exposed to ultraviolet light for 30 min to obtain a polylactic acid substrate PLLA-BP containing a photoinitiator;

[0083] (2) Prepare a monomer aqueous solution containing 10 wt% polyethylene glycol monomethyl ether monomethacrylate (MA-PEG2000) and 0.5 wt% methacryloyl RGD polypeptide (MA-RGD), soak the PLLA-BP obtained in step (1) in the monomer solution, flow nitrogen for 30 min, and then irradiate with ultraviolet light for 30 min to obtain a comparison sample PLLA-PEG / RGD whose surface does not contain a hydrogen sulfide donor coating.

[0084] Test example

[0085] 1. Surface element analysis

[0086] The PLLA-PEG-ABTA / RGD obtained in Example 1, the PLLA-PEG / RGD obtained in Comparative Example 1, and the blank substrate PLLA without coating treatment were subjected to XPS surface element analysis to detect the characteristic element S of the hydrogen sulfide donor. The results are as follows: Figure 1 shown.

[0087] 2. Hydrogen sulfide release rate

[0088] The hydrogen sulfide release rate was determined by the methylene blue method. Figure 2 shown.

[0089] 3. Subcutaneous implantation experiment

[0090] Healthy Sprague Dawley (SD) rats weighing about 300 g were selected. Under anesthesia, PLLA, PLLA-PEG / RGD, and PLLA-PEG-ABTA / RGD were subcutaneously implanted into the back of the rats. After 15 and 30 days, the implanted samples and surrounding tissues were removed, rinsed with PBS, and fixed with 2.5% paraformaldehyde. The fixed tissues were stained with hematoxylin-eosin (H&E) for histological analysis. The results are shown in Figure 2. Figure 3 shown.

[0091] Depend on Figure 3 It can be seen that the anti-inflammatory and pro-repair coating based on hydrogen sulfide donor has a good anti-inflammatory effect and significantly reduces the thickness of the fiber capsule on the surface of the material.

[0092] 4. Platelet Adhesion and Activation

[0093] Take about 10 mL of rabbit venous blood and centrifuge it at 2000 rpm for 15 minutes. Subsequently, the supernatant was further centrifuged at 3500 rpm for 10 minutes, and platelet-rich plasma (PRP) was collected from the bottom of the centrifuge tube with a syringe. The sample was placed in a 48-well plate, and 500 μL of PRP and 20 μM glutathione (GSH) were added to each well. The plate was then placed in a cell culture incubator at 37 °C for 1 hour, and the platelets adhered to the surface of the material were observed by scanning electron microscopy (SEM). The results are as follows Figure 4 shown.

[0094] Depend on Figure 4 It can be seen that the anti-inflammatory and pro-repair coating based on hydrogen sulfide donor can effectively reduce the number and activation degree of platelet adhesion on the material surface.

[0095] 5. Endothelial cell adhesion and proliferation

[0096] Human umbilical vein endothelial cells (ECs, obtained from West China Hospital of Sichuan University) were cultured at 37 °C and 5% CO2. The culture medium used was Dulbecco's modified DMEM supplemented with 10% fetal bovine serum (FBS), 1% penicillin-streptomycin, and 20 μM glutathione (GSH). ECs were cultured at 3 × 10 4The cells were directly inoculated on the sample surface at a density of 10 cells / mL. After incubation for 1 and 3 days, the cell adhesion and proliferation were observed under a microscope. Figure 5 shown.

[0097] 6. Endothelial cell migration

[0098] The Transwell cell migration assay was used to study the effect of hydrogen sulfide donors on endothelial cell migration. Figure 6 shown.

[0099] from Figure 5 and Figure 6 It can be seen that the anti-inflammatory and pro-repair coating based on hydrogen sulfide donor can significantly enhance the adhesion, proliferation and migration ability of endothelial cells, thereby accelerating the tissue repair process.

[0100] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor, characterized in that: The coating contains a hydrogen sulfide donor; the hydrogen sulfide donor releases hydrogen sulfide or a hydrogen sulfide precursor spontaneously or under external stimulation; and The hydrogen sulfide donor coating is covalently attached to the surface of the substrate; the covalent attachment is achieved by route one or route two: Path 1: The initiator is fixed on the surface of the substrate or below by chemical means or physical adsorption; the initiator generates free radicals to initiate the polymerization of the hydrogen sulfide donor monomer; Path 2: The chemical bonds on the substrate surface are broken by irradiation, and the generated free radicals initiate the polymerization of hydrogen sulfide donor monomers; The hydrogen sulfide donor monomer includes one or more carbon-carbon double bonds and one or more hydrogen sulfide donors; the carbon-carbon double bonds are derived from the carbon-carbon double bonds introduced by chemical modification of the hydrogen sulfide donor; The hydrogen sulfide donor monomer is obtained by chemical reaction of compound I and compound II: Compound I is a compound containing a carbon-carbon double bond and a reactive group A; Compound II is a compound containing a hydrogen sulfide donor and a reactive group B; The reactive group A includes at least one of carboxyl, acyl chloride, acid anhydride, epoxy, active ester, hydroxyl, amino, amino hydrochloride, carbon-carbon double bond, carbon-carbon triple bond, isocyanate, and thioisocyanate; The conditions of the reactive group A and the reactive group B include at least one of the characteristics (1) to (4): (1) When the reactive group A includes at least one of carboxyl, acyl chloride, anhydride, epoxy, active ester, isocyanate, and thioisocyanate, the reactive group B includes at least one of amino, hydroxyl, and thiol; (2) When the reactive group A includes at least one of amino and hydroxylamino hydrochloride, the reactive group B includes at least one of carboxyl, acyl chloride, acid anhydride, epoxy, active ester, isocyanate, and thioisocyanate; (3) When the reactive group A includes a carbon-carbon double bond, the reactive group B includes at least one of an amino group, an amino hydrochloride, and a thiol group; (4) When the reactive group A includes a carbon-carbon triple bond, the reactive group B includes at least one of an amino group, an amino hydrochloride group, a thiol group, and an azide group.

2. The anti-inflammatory and pro-repair coating based on hydrogen sulfide donor according to claim 1, characterized in that: The hydrogen sulfide donor includes at least one of the following groups: 。 3. The anti-inflammatory and pro-repair coating based on hydrogen sulfide donor according to any one of claims 1 to 2, characterized in that: The external stimulation includes at least one of chemical stimulation, light stimulation, thermal stimulation and ultrasonic stimulation.

4. The anti-inflammatory and pro-repair coating based on hydrogen sulfide donor according to claim 3, characterized in that: The chemical stimulation includes at least one of thiol compounds and reactive oxygen; the thiol compounds include at least one of cysteine ​​and glutathione; the reactive oxygen includes at least one of hydrogen peroxide, superoxide anion, organic peroxide, lipid peroxide, and peroxynitrite.

5. A method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor as claimed in any one of claims 1 to 4, characterized in that: The preparation method comprising route 1 comprises the following steps: S1: pre-treating the substrate by immersing it in a solution containing an initiator to obtain a first treated body; S2 the first treated body is immersed in a solution containing a hydrogen sulfide donor monomer to obtain a second treated body; S3 The second treated body is polymerized on the surface by an initiator to obtain an anti-inflammatory and repair-promoting coating.

6. A method for preparing an anti-inflammatory and pro-repair coating based on a hydrogen sulfide donor as claimed in any one of claims 1 to 4, characterized in that: The preparation method comprising the second approach comprises the following steps: S1: soaking the substrate in a solution containing a hydrogen sulfide donor monomer to obtain a first treated body; S2 The first treated body is irradiated to induce polymerization to obtain an anti-inflammatory and repair-promoting coating.

7. Use of the anti-inflammatory and pro-repairing coating as described in any one of claims 1 to 4, or the anti-inflammatory and pro-repairing coating obtained by the preparation method as described in claim 5, or the anti-inflammatory and pro-repairing coating obtained by the preparation method as described in claim 6 in the preparation of biomedical materials.

Citation Information

Patent Citations

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