CN120682681A - Endothelialization-promoting antifouling developing coating material and its preparation method and application - Google Patents
Endothelialization-promoting antifouling developing coating material and its preparation method and applicationInfo
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- CN120682681A CN120682681A CN202510892695.7A CN202510892695A CN120682681A CN 120682681 A CN120682681 A CN 120682681A CN 202510892695 A CN202510892695 A CN 202510892695A CN 120682681 A CN120682681 A CN 120682681A
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Abstract
本发明涉及一种促内皮化防污显影涂层材料及其制备方法和应用。所述促内皮化防污显影涂层材料通过硅氧烷修饰的显影剂与改性磷酸胆碱聚合物反应得到；所述改性磷酸胆碱聚合物通过含双键单体共聚得到，所述含双键单体包括含双键磷酸胆碱单体、促内皮化单体和硅氧烷单体的组合。本发明的促内皮化防污显影涂层材料将硅氧烷修饰的显影剂与改性磷酸胆碱聚合物连接。硅氧烷修饰的显影剂提高显影功能，改性磷酸胆碱聚合物提供防污和促内皮化功能，形成了兼具防污、显影及促内皮化功能的复合涂层。
The present invention relates to an endothelialization-promoting antifouling developing coating material, and its preparation method and application. The endothelialization-promoting antifouling developing coating material is obtained by reacting a siloxane-modified developer with a modified phosphorylcholine polymer; the modified phosphorylcholine polymer is obtained by copolymerizing double-bond-containing monomers, and the double-bond-containing monomers include a combination of double-bond phosphorylcholine monomers, endothelialization-promoting monomers, and siloxane monomers. The endothelialization-promoting antifouling developing coating material of the present invention connects a siloxane-modified developer with a modified phosphorylcholine polymer. The siloxane-modified developer improves the developing function, and the modified phosphorylcholine polymer provides antifouling and endothelialization-promoting functions, forming a composite coating with antifouling, developing, and endothelialization-promoting functions.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to an endothelialization-promoting antifouling developing coating material and a preparation method and application thereof.
Background
In the fields of medical imaging and implantable medical devices, development of a medical developing coating is a key for improving diagnosis and treatment accuracy and device safety. With the development of interventional therapy technology, the requirement of developing coating has been expanded from single imaging function to multifunctional integration, including antifouling (antithrombotic, antibacterial) and endothelialization promoting properties, so as to meet the requirement of complex clinical scenes.
Conventional development coatings rely primarily on iodine compounds (such as iohexol) or heavy metal containing developers to perform imaging functions through interactions with X-rays. However, such coatings face problems of poor developer dissolution, biocompatibility, and lack of active anti-fouling capability in long term implantation, which is prone to thrombus or infection. In order to solve the anti-fouling requirement, the prior art utilizes hydrophilic or cell membrane-imitating structures to reduce protein and bacterial adsorption by introducing anti-fouling materials such as phosphorylcholine polymer, polyethylene glycol (PEG) and the like. Although the antifouling performance of the coating can be improved, the development function of the coating is often attenuated due to insufficient compatibility of a developer and an antifouling group, and phase separation is easy to occur in a body fluid environment, so that the stability of the coating is reduced.
In recent years, researchers have attempted to synergistically integrate development with antifouling functions. For example, the binding force of the coating to the substrate is enhanced by the siloxane groups while the iodine groups are utilized to provide a developing function. However, such coatings have two major drawbacks, namely, firstly, the simple physical mixing of the developer and the anti-fouling group results in loss of functional components during long-term use, and secondly, the surface of the coating is biologically inert, while the adhesion of pollutants can be reduced, the adhesion and proliferation of endothelial cells are inhibited, the endothelialization of the surface of an implantation instrument (such as a cardiovascular stent) is delayed, and the risk of restenosis after operation is increased.
CN103467729a discloses a polyethylene glycol-polyamino acid-polyester triblock polymer which can form amphiphilic micelles as carrier of contrast agent. However, the contrast agent and the anti-fouling group are combined together through physical mixing, so that functional components are easy to lose after long-term use.
CN119219844a discloses an antifouling developing coating material, which combines antifouling and developing through covalent bonding technology, and can ensure stability and durability of developing effect. But the surface of the material coating is biologically inert, so that the adhesion and proliferation of endothelial cells are inhibited.
CN119101421a discloses an antifouling developing coating material, which connects platinum nano particles with modified phosphorylcholine polymer, so that the antifouling developing coating material has excellent antifouling property and developing property. And the siloxane groups in the antifouling unit can form covalent bonding with the surface of the substrate so as to firmly bond the coating on the substrate, thereby ensuring the bonding stability and safety of the antifouling developing coating material on the substrate. However, the developer of the material is platinum nano particles, and is connected with polymer chains through electrostatic action, so that the material has poor stability.
In the field of endothelialising coatings, the prior art has mainly promoted endothelial cell growth by grafting bioactive molecules. For example, vascular stent coatings modified with RGD peptides can specifically bind to endothelial cell integrin receptors, accelerating endothelial layer repair. However, such coatings lack visualization and anti-fouling functions, and physical adsorption or simple covalent attachment of RGD peptides tends to result in shedding or loss of activity, especially in poor stability under the action of blood flow shear forces. Furthermore, heparin coating has the dual effects of anticoagulation and endothelialization, but its biological activity depends on precise molecular weight control and there is a risk of inducing thrombocytopenia.
In summary, in the prior art, the developing coating, the antifouling coating and the endothelialization promoting coating are functionally fractured, so that the cooperative requirements of the implantation instrument on developing monitoring, antifouling and anti-thrombus and rapid endothelial repair are difficult to meet. Therefore, how to effectively combine the functions of development, antifouling and endothelial repair remains a challenging problem, and needs to be further solved.
Disclosure of Invention
In order to solve the technical problems, the invention provides an endothelialization-promoting antifouling developing coating material, and a preparation method and application thereof. The endothelialization anti-fouling development coating material meets the cooperative requirements of an implantation instrument on development monitoring, anti-fouling anti-embolism and rapid endothelial repair.
To achieve the purpose, the invention adopts the following technical scheme:
In a first aspect, the present invention provides an endothelialization-promoting anti-fouling development coating material obtained by reacting a siloxane-modified developer with a modified phosphorylcholine polymer;
The modified phosphorylcholine polymer is obtained by copolymerizing double bond-containing monomers, wherein the double bond-containing monomers comprise a combination of double bond-containing phosphorylcholine monomers, endothelialization-promoting monomers and siloxane monomers;
the endothelialization-promoting monomer is obtained by reacting endothelialization-promoting polypeptide with NHS-polyethylene glycol-acrylic ester;
the structure of the siloxane monomer is shown as a formula I: x comprises hydrogen and/or methyl, R comprises a tris (trimethylsiloxy) silane group and/or a trimethoxysilane group;
The R group is linked to a siloxane-modified developer by a chemical bond.
The endothelialization-promoting antifouling developing coating material of the invention connects a siloxane-modified developer with a modified phosphorylcholine polymer. The siloxane modified developer improves the developing function, and the modified phosphorylcholine polymer provides the functions of antifouling and endothelialization promotion, so that a composite coating with the functions of antifouling, developing and endothelialization promotion is formed. The invention integrates three functions into one polymer by selecting specific polymerization monomers, and the addition of siloxane monomers can also improve the bonding effect of the material.
Preferably, the double bond-containing monomer comprises the following components, by mole, 10-30 parts of double bond-containing phosphorylcholine monomer, 10-30 parts of siloxane monomer and 1-5 parts of endothelialization-promoting monomer.
The molar fraction of the double bond-containing phosphorylcholine monomer may be, for example, 15 parts, 18 parts, 20 parts, 25 parts, 28 parts, or the like.
The molar fraction of the siloxane monomer may be, for example, 15 parts, 18 parts, 20 parts, 25 parts, 28 parts, or the like.
The molar fraction of the endothelialization promoting monomer may be, for example, 2 parts, 3 parts, 4 parts, or the like.
Preferably, the double bond-containing monomer comprises, by mass, 1-5 parts of double bond-containing phosphorylcholine monomer, 1-10 parts of siloxane monomer and 1-5 parts of endothelialization-promoting monomer.
The double bond-containing phosphorylcholine monomer may be 2 parts, 3 parts, 4 parts, or the like, for example.
The mass fraction of the siloxane monomer may be, for example, 2 parts, 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, or the like.
The mass fraction of the endothelialization promoting monomer can be, for example, 2 parts, 3 parts or 4 parts.
Preferably, the double bond-containing phosphorylcholine monomer comprises 2-methacryloyloxyethyl phosphorylcholine and/or acryloyloxyethyl phosphorylcholine.
Preferably, the siloxane monomer comprises any one or a combination of at least two of the following compounds:
preferably, the sequence of the endothelialising promoting polypeptide comprises either GGYIGSR or GGREDV or a combination of both.
Preferably, the siloxane-modified developer is obtained by reacting a silane coupling agent with a developer.
Preferably, the silane coupling agent comprisesAny one or a combination of at least two of 3-glycidoxypropyl triethoxysilane, 3-glycidoxypropyl methyl dimethoxysilane or 2- (3, 4-epoxycyclohexane) ethyl triethoxysilane.
Preferably, the developer comprises any one or a combination of at least two of iohexol, iohexol hydrolysate, iopromide, diatrizoic amine, sodium diatrizoate, iodized oil or iodixanol, further preferably iohexol and/or iohexol hydrolysate.
Preferably, the siloxane-modified developer is linked to the R groups by Si-O-Si bonds.
In a second aspect, the present invention provides a method for preparing the endothelialization-promoting antifouling developing coating material according to the first aspect, the method comprising the steps of:
carrying out copolymerization reaction on a siloxane monomer, an endothelialization promoting monomer and a double bond-containing phosphorylcholine monomer to obtain a modified phosphorylcholine polymer;
And (3) performing a first hydrolytic condensation reaction on the siloxane modified developer and the modified phosphorylcholine polymer to obtain the endothelialization-promoting antifouling development coating material.
Preferably, the preparation method of the endothelialization-promoting monomer comprises the following steps:
and (3) carrying out condensation reaction on the endothelialization-promoting polypeptide and NHS-polyethylene glycol-acrylic ester to obtain the endothelialization-promoting monomer.
Preferably, the condensation reaction is carried out in the presence of a catalyst.
Preferably, the catalyst comprises triethylamine.
Preferably, the molar ratio of the endothelin-promoting polypeptide to NHS-polyethylene glycol-acrylate is (1-5): 1, for example, it may be 2:1, 3:1, or 4:1, etc.
Preferably, the temperature of the condensation reaction is 15-45 ℃, for example, 20 ℃, 25 ℃, 30 ℃, 35 ℃, 40 ℃, etc., preferably 28-32 ℃.
Preferably, the time of the condensation reaction is 1 to 5 hours, for example, 1.5 hours, 2.5 hours, 3 hours, 3.5 hours, 4.5 hours, etc., preferably 2 to 4 hours.
Preferably, the solvent for the condensation reaction comprises N, N-dimethylformamide.
Preferably, the condensation reaction is carried out under the protection of a protective gas.
Preferably, the shielding gas comprises nitrogen.
Preferably, the method for preparing the siloxane-modified developer comprises the following steps:
and carrying out a second hydrolytic condensation reaction on the developer and the silane coupling agent to obtain the siloxane modified developer.
Preferably, the molar ratio of the developer to the silane coupling agent is (1-3): 1, for example, it may be 1.5:1, 2:1, 2.5:1, or the like.
Preferably, the temperature of the second hydrolytic condensation reaction is 15 to 30 ℃, for example, 16 ℃, 18 ℃, 23 ℃, 26 ℃, 28 ℃, etc., preferably 20 to 25 ℃.
Preferably, the second hydrolytic condensation reaction time is 12 to 24 hours, for example, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, or the like.
Preferably, the solvent of the second hydrolytic condensation reaction includes a mixture of water and an organic solvent including any one or a combination of at least two of methanol, isopropanol, n-propanol, dimethyl sulfoxide.
Preferably, the copolymerization is carried out in the presence of an initiator.
Preferably, the initiator comprises any one or a combination of at least two of azobisisobutyronitrile, dibenzoyl peroxide or 4,4' -azobis (4-cyanovaleric acid), preferably azobisisobutyronitrile.
Preferably, the copolymerization is carried out in the presence of a solvent.
Preferably, the solvent for the copolymerization reaction includes any one or a combination of at least two of n-propanol, dimethyl sulfoxide, tetrahydrofuran, toluene or ethyl acetate, preferably n-propanol.
Preferably, the copolymerization is carried out in the presence of a chain transfer agent.
Preferably, the chain transfer agent of the copolymerization reaction comprises any one or a combination of at least two of benzyl N, N-dimethyldithiocarbamate, polyethylene glycol modified trithiocarbonate or 4-cyano-4- (thiobenzoyl) pentanoic acid, preferably 4-cyano-4- (thiobenzoyl) pentanoic acid.
Preferably, the temperature of the copolymerization reaction is 60 to 70 ℃, and may be 62 ℃, 64 ℃, 66 ℃, 68 ℃ or the like, for example.
Preferably, the time of the copolymerization reaction is 28-56h, for example, 30h, 35h, 40h, 45h, 50h or 55h, etc.
Preferably, the temperature of the first hydrolytic condensation reaction is 20 to 30 ℃, for example, 22 ℃, 24 ℃, 26 ℃, 28 ℃, or the like.
Preferably, the time of the first hydrolytic condensation reaction is 3 to 12 hours, for example, 4 hours, 6 hours, 8 hours, 10 hours, etc., preferably 5 to 7 hours.
Preferably, the first hydrolytic condensation reaction is carried out in the presence of a solvent.
Preferably, the solvent of the first hydrolytic condensation reaction includes a mixture of water and an organic solvent including any one or a combination of at least two of methanol, isopropanol, n-propanol, dimethyl sulfoxide.
Preferably, in the first hydrolytic condensation reaction, the molar ratio of the siloxane modified developer to siloxane repeating units in the modified phosphorylcholine polymer is (0.5-2): 1, for example 0.75:1, 1:1, 1.25:1, 1.6:1, or 1.75:1, etc., more preferably (0.8-1.5): 1.
The invention can improve the adhesive force of the coating while providing the developing performance by adjusting the mol ratio of the siloxane modified developer to the siloxane repeating unit in the modified phosphorylcholine polymer to be (0.5-2): 1. If the number of moles of the siloxane-modified developer is too large, the anti-fouling effect is lowered, and if the number of moles of the siloxane repeating units in the modified phosphorylcholine polymer is too large, the developing effect is lowered.
In a third aspect, the present invention provides the use of a endothelialisation promoting antifouling developing coating material according to the first aspect in a medical device, a medical material or an optical lens.
In a fourth aspect, the present invention provides the use of a endothelialisation-promoting antifouling developing coating material as described in the first aspect for coating a surface of a substrate.
Preferably, the substrate surface comprises any one or a combination of at least two of a silicon-based surface, a glass substrate surface, a metal substrate surface or a high molecular polymer substrate surface.
Preferably, the polymer comprises any one or a combination of at least two of silicone rubber, polyethylene, polypropylene, polyvinyl chloride, polystyrene or polyurethane.
The endothelialization anti-fouling development coating material has universality, can be combined with any silicon-based substrate through hydroxyl groups on the surface of a substrate by a silicon-oxygen bond, comprises glass, silica gel sheets, metal oxide surfaces and the like, is combined with other substrate surfaces through hydrophobic action or Van der Waals force, and is widely suitable for different clinical and laboratory scenes, and the requirements of different users are met.
Compared with the prior art, the invention has at least the following beneficial effects:
(1) The endothelialization-promoting antifouling developing coating material has antifouling, developing and endothelialization-promoting functions. Compared with the traditional developing coating, the material has the advantages of remarkably improving the antifouling performance, effectively inhibiting the nonspecific adsorption of bacteria, reducing the risk of infection, embedding the developer into a coating network in a chemical bond form, avoiding water-soluble loss, ensuring long-term stability of developing signals in vivo, and promoting the adhesion and proliferation of endothelial cells through the endothelialization promoting polypeptide of covalent bonding.
(2) The invention can promote the stable covalent bonding of the coating and various surfaces by adjusting the molar ratio of the siloxane modified developer to the siloxane repeating units in the modified phosphorylcholine polymer.
Drawings
FIG. 1A is a nuclear magnetic hydrogen spectrum of example 2;
FIG. 1B is a nuclear magnetic hydrogen spectrum of example 1;
FIG. 1C is a nuclear magnetic hydrogen spectrum of example 3;
FIG. 1D is the photoelectron spectroscopy of examples 1-3;
FIG. 2A is a graph of the results of an antibacterial adhesion test of the endothelialization anti-fouling development coating material of example 1;
FIG. 2B is a graph of the quantitative analysis results of the antibacterial adhesion test of the endothelialization antifouling development of the coating material of example 1;
FIG. 3A is a graph showing the development test results of the endothelialization antifouling development of the coating material of example 1 in rats;
FIG. 3B is a graph showing the quantitative analysis of the development of the endothelialization-promoting antifouling development of the coating material of example 1 in rat tissue;
FIG. 4A is a graph of endothelialization test results of the endothelialization-promoting anti-fouling development coating materials of example 1, example 4, and comparative example 1 on a glass substrate;
FIG. 4B is a graph showing the quantitative analysis of endothelialization of the endothelialization-promoting stain resist development coating materials of example 1, example 4, and comparative example 1 on a glass substrate.
Detailed Description
The technical scheme of the invention is further described below by the specific embodiments with reference to the accompanying drawings. The following examples are merely illustrative of the present invention and are not intended to represent or limit the scope of the invention as defined in the claims.
Example 1
The embodiment provides an endothelialization anti-fouling development coating material, and the preparation method of the endothelialization anti-fouling development coating material comprises the following steps:
(1) Preparation of endothelialising monomers
2.0Mol of polypeptide (GGYIGSR) is dissolved in anhydrous DMF, the anhydrous DMF is placed in ice bath, 1mol of DMF solution of NHS-PEG-acrylic ester (manufacturer: MCE, brand: HY-172354A) is slowly dripped into the anhydrous DMF, the mixture is stirred for 3 hours at room temperature, excessive glycine is added, the mixture is incubated for 10 minutes at room temperature, quenching reaction is carried out, micromolecular substances are removed by dialysis, and the endothelialization-promoting monomer is obtained by freeze drying.
(2) Preparation of modified phosphorylcholine polymers
2-Methacryloyloxyethyl phosphorylcholine (3 g), 4-cyano-4- (thiobenzoyl) pentanoic acid (3 g), azobisisobutyronitrile (AIBN, 0.16 g) were dissolved in n-propanol (100 mL). The temperature is slowly raised to 65 ℃ under the protection of nitrogen, and the reaction is stirred for 24 hours. Then, methacryloxypropyl tris (trimethylsiloxy) silane (8 mL) and 1.5g of endothelialising monomer were added, and the reaction was continued for 24 hours. The resulting solution was precipitated in diethyl ether (200 mL), filtered and dried to give a modified phosphorylcholine polymer.
(3) Preparation of siloxane-modified developer
Dissolving iohexol hydrolysate (5 g) in 10mL of methanol/water binary mixed solvent (the volume ratio of methanol/water is 1:1), adding potassium hydroxide (1.67 g), stirring at room temperature, and dissolving with ultrasound to obtain pale yellow solution, mixing with water, stirring, and stirring(2G) Dissolved in 10mL of a methanol/water binary mixed solvent, and then mixed with a pale yellow solution, and stirred at room temperature overnight. The reacted product was then extracted from the methanol/water binary solvent with ethyl acetate to the organic phase and the extraction was repeated 5 times. The reaction mixture was then evaporated with a rotary evaporator to remove the organic solvent, followed by dialysis and liquid phase treatment to give a siloxane-modified developer.
(4) Preparation of endothelialization-promoting antifouling developing coating material
The siloxane modified developer and the modified phosphorylcholine polymer are mixed in a methanol/water binary solvent (the volume ratio of methanol to water is 1:1), and the mol ratio of the siloxane modified developer to siloxane repeating units in the modified phosphorylcholine polymer is 1:1. Stirring for 6h at room temperature, extracting with ethyl acetate, and steaming to obtain the endothelialization-promoting antifouling development coating material.
Example 2
This example provides an endothelialization-promoting antifouling developing coating material differing from example 1 only in that (4) the preparation of the endothelialization-promoting antifouling developing coating material comprises the steps of mixing a siloxane-modified developer and a modified phosphorylcholine polymer in a methanol/water binary solvent (methanol/water volume ratio of 1:1) and a molar ratio of the siloxane-modified developer to siloxane repeating units in the modified phosphorylcholine polymer of 2:1. Stirring for 6h at room temperature, extracting with ethyl acetate, and steaming to obtain the endothelialization-promoting antifouling development coating material.
Example 3
This example provides an endothelialization-promoting antifouling developing coating material differing from example 1 only in that (4) the preparation of the endothelialization-promoting antifouling developing coating material comprises the steps of mixing a siloxane-modified developer and a modified phosphorylcholine polymer in a methanol/water binary solvent (methanol/water volume ratio of 1:1) and a molar ratio of the siloxane-modified developer to siloxane repeating units in the modified phosphorylcholine polymer of 1:2. Stirring for 6h at room temperature, extracting with ethyl acetate, and steaming to obtain the endothelialization-promoting antifouling development coating material.
As shown in FIG. 1, nuclear magnetism and photoelectron spectroscopy (XPS) structural characterization is carried out on the endothelialization anti-fouling development coating materials provided in examples 1-3, vibration peaks exist at 7.3ppm and 3.55ppm on a nuclear magnetic resonance hydrogen spectrum curve, the vibration peaks correspond to an iodophenyl group in a development monomer and a siloxane group in an anti-fouling molecule respectively, peaks are detected at 285eV, 532eV, 400eV and 620eV on an XPS curve, C, O, N and I elements respectively, and the content of the I element of a sample rises from 2% to 4% along with the increase of the proportion of the iodine-containing development monomer, so that successful polymerization of the iodine-containing development monomer and the anti-fouling molecule is proved.
Example 4
An endothelialization anti-fouling development coating material which differs from example 1 only in that the polypeptide sequence of step (1) is GGREDV and the rest of the steps are the same as in example 1.
Comparative example 1
An endothelialization-promoting antifouling developing coating material is different from example 1 in that no endothelialization-promoting monomer is added in step (2), and the rest of the steps are the same as in example 1.
Test method
(1) Antibacterial adhesion test
The antibacterial adsorption capacity of the coatings was tested using candida albicans (c.albicans), escherichia coli (e.coli) and staphylococcus aureus (s.aureus). The endothelialization anti-fouling development coating material is coated on the surface of glass, a sample is soaked in three living bacteria liquids with high concentration (10 8/mL), living bacteria are replaced once a day, the living bacteria are taken out and dried after soaking for one week, and the bacterial number on the living bacteria is observed by using a Scanning Electron Microscope (SEM). The solvent is dialysis fluid, so that bacterial activity is guaranteed, and the blank control group is a sample without coating material.
The antibacterial adhesion test results are shown in fig. 2A, where under the adsorption of three different bacteria, there were significantly large colonies on the control group not coated with the anti-fouling development coating after one week, whereas no significant colony growth was observed on the sample coated with the anti-fouling development coating. Further, the adsorbed colonies were quantitatively analyzed, and as a result, as shown in fig. 2B, the sample using the anti-fouling developing coating significantly reduced bacterial adhesion, and after one week, the bacterial adhesion amount was reduced by 90%.
(2) X-ray development test
The antifouling developing coating material is coated on a silica gel hose and placed in a rat body, the concentration of a coating solution is 100mg/mL and 200mg/mL, a control group is a silica gel hose which is not coated with the antifouling developing coating material, and a medical X-ray irradiator (manufacturer: frame-shaped De core; model: XVS 2530) is used for shooting.
The development effect of the anti-fouling development coating material of the invention is far higher than that of a blank control group, and the development strength in the interior of a rat can be improved along with the increase of the concentration by quantitatively analyzing the development part through Image J software. Therefore, the antifouling developing coating material has a strong X-ray developing effect.
(3) Test for endothelialization promotion
The endothelialization-promoting antifouling developing coating material is coated on the surface of glass, an uncoated group is used as a negative control, an antifouling coating without the endothelialization-promoting group is used as a positive control, and the coating is cultured for 0h,4h and24 h to observe the cell adhesion condition. (cytoinformation: HUVEC cells; cultured at 37 ℃,5% CO 2)
Fig. 4A is a graph showing cell adhesion of the endothelialization-promoting anti-fouling development coating on the glass substrate at different times, and fig. 4B is a statistical graph showing cell adhesion quantity of the 24-hour endothelialization-promoting anti-fouling development coating on the glass substrate, so that the endothelialization-promoting effect of the invention is far higher than that of a positive control group, and the endothelialization-promoting effect of the invention is stronger.
The applicant declares that the above is only a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and it should be apparent to those skilled in the art that any changes or substitutions that are easily conceivable within the technical scope of the present invention disclosed by the present invention fall within the scope of the present invention and the disclosure.
Claims (10)
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