阅读说明：本技术 一种具有优异长效抗凝血及抗菌抗污性能的生物医用涂层及其制备方法 (Biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances and preparation method thereof ) 是由 王云兵 刘坤鹏 罗日方 杨立 张凡军 于 2021-09-02 设计创作，主要内容包括：本发明提供了一种具有优异长效抗凝血及抗菌抗污性能的生物医用涂层及其制备方法,制备方法,依次包括以下步骤：(1)对基底材料进行清洁,然后进行引发剂的固定；(2)在光照条件下,将两性离子单体与含双键和羧基的单体反应1-3h,清洗,得医用涂层；(3)将步骤(2)所得医用涂层置于酸性环境中,用混合液进行活化,然后加入抗菌剂反应24h,再依次经清洗和干燥,得具有优异长效抗凝血及抗菌抗污性能的生物医用涂层。本发明还包括采用上述方法制得的生物医用涂层。本发明基于含两性离子水凝胶的良好血液相容性、阻抗蛋白吸附功能和抗菌剂的杀菌作用,实现在血液接触器械表面抗凝、抗菌,抗污的目的。(The invention provides a biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances and a preparation method thereof, wherein the preparation method sequentially comprises the following steps: (1) cleaning the substrate material, and then fixing an initiator; (2) under the condition of illumination, reacting a zwitterionic monomer with a monomer containing double bonds and carboxyl for 1-3h, and cleaning to obtain a medical coating; (3) and (3) placing the medical coating obtained in the step (2) in an acid environment, activating by using the mixed solution, adding an antibacterial agent to react for 24 hours, and then sequentially cleaning and drying to obtain the biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances. The invention also comprises the biomedical coating prepared by the method. The invention realizes the purposes of anticoagulation, antibiosis and stain resistance on the surface of a blood contact apparatus based on the good blood compatibility, the protein-resistant adsorption function and the sterilization function of an antibacterial agent of the hydrogel containing zwitterion.)

1. A preparation method of a biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances is characterized by sequentially comprising the following steps:

(1) cleaning the substrate material, and then fixing an initiator;

(2) under the condition of illumination, reacting a zwitterionic monomer with a monomer containing double bonds and carboxyl for 1-3h, and cleaning to obtain a medical coating;

(3) and (3) placing the medical coating obtained in the step (2) in an acid environment, activating by using the mixed solution, adding an antibacterial agent to react for 24 hours, and then sequentially cleaning and drying to obtain the biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances.

2. The method for preparing biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance according to claim 1, wherein the substrate material is polymer-based biomaterial or polymer-based composite biomaterial.

3. The method of claim 1, wherein the initiator is a monomer containing a halogen bond, benzophenone, or azobisisobutyronitrile.

4. The method of claim 1 wherein said zwitterion is 2- (methacryloyloxy) ethyl-2- (trimethylamino) ethyl phosphate, [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide or 3- [ [2- (methacryloyloxy) ethyl ] dimethyl ammonium ] propionate.

5. The method of preparing biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance according to claim 1, wherein the monomer containing double bond and carboxyl is methacrylic acid.

6. The method of claim 1, wherein the mixture is a mixture of 0.1-0.5M 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 0.05-0.2M N-hydroxysuccinimide ester.

7. The method of claim 1, wherein the antimicrobial agent is an antibiotic or an antimicrobial peptide at a concentration of 1-10 mg/mL.

8. The method of claim 1, wherein the concentration of the zwitterionic monomer is 2.5-15 wt% and the concentration of the monomer containing double bond and carboxyl is 5-25 wt%.

9. The method for preparing biomedical coating with excellent long-acting anticoagulant, antibacterial and antifouling properties according to claim 1, wherein in the step (3), the coating is washed for 10-20min for 2-4 times and dried under nitrogen.

10. The biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance prepared by the preparation method of the biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance of any one of claims 1-9.

Technical Field

The invention belongs to the technical field of biomedical materials, and particularly relates to a biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performances and a preparation method thereof.

Background

Bacterial infections and thrombosis are two major complications faced by blood-contacting instruments and materials, and these problems can lead to implant failure, which in turn can cause significant pain to the patient. In clinical practice, the problem is often solved by the combination of thrombolytic drugs and antibiotics. However, overuse of thrombolytic drugs and antibiotics carries the risk of massive hemorrhage and the development of drug-resistant bacteria. Therefore, surface functionalization can be an effective means for improving the antibacterial and antithrombotic property of medical instruments and implants.

Sterilization and anti-fouling on the surface of materials are two strategies for reducing bacterial infection, the former is realized by doping heavy metal ions, coating antibiotics and coupling cationic polymers. The latter is achieved by grafting hydrophilic polymers, such as polyethylene glycol (PEG) and zwitterionic polymers. Water interacts with the hydrophilic component to form a hydrated layer. The hydrophilic component can generate steric exclusion, and nonspecific adsorption such as protein, bacteria and the like is remarkably reduced. At the same time, anti-fouling strategies are also effective against thrombi, since they have the same principle, being able to reduce the absorption and activation of platelets and fibrin. However, the anti-fouling strategy alone is not sufficient to prevent the adhesion and growth of bacteria for long periods of time. In addition, the anti-fouling surface is unable to inactivate bacteria, which can lead to infection of the blood or other parts. At the same time, the bactericidal surface also has certain disadvantages, such as short life, high toxicity, poor blood compatibility, etc., which limits its application in blood-related medical devices. From this point of view, a single functional surface with antifouling or bactericidal properties alone is not sufficient in clinical applications. At the same time, the stability of the functional surface is also a serious problem. Unstable, easily degradable surfaces do not function continuously. Therefore, a high-stability dual-functional surface with both antifouling and bactericidal properties is a feasible solution to thrombus and bacterial infection. Antimicrobial agents come in a wide variety of forms, including antibiotics, heavy metal ions, cationic substances, antimicrobial peptides, and the like. Antibiotics are an antimicrobial agent that has been used clinically in a wide range of applications, and their safety and effectiveness have been proven and tested. Antibacterial peptide is a peptide substance naturally existing in the body and is an important component of innate immunity. Antimicrobial peptides are considered to be valuable drugs that exert desirable antimicrobial properties. Many researchers have applied antibacterial peptides to surface modification, but when these peptides are immobilized as an antibacterial coating, there are many problems such as greatly reduced antibacterial activity, easy adsorption of proteins and dead bacteria, because the cationic nature of the antibacterial peptide can trigger immune response and inflammation and may block antibacterial functional groups. More importantly, due to the cationic nature of AMPs, they also readily adsorb and activate platelets, increasing the risk of thrombosis, and may also induce hemolysis of red blood cells, limiting their use in blood contacts or grafts. Among the reported antifouling surface modifications, hydrogel coating is a promising strategy. Since hydrogels have good anti-fouling properties and hemocompatibility and adjustable chemical structures. In addition, the hydrogel coating with the thickness of micron is more stable than the hydrogel coating with the thickness of nanometer, has higher strength, is firmly combined and is not easy to fall off, and the hydrogel coating can be conveniently loaded with different and abundant medicaments to complete various functions, such as antibiosis, anti-inflammation, anticoagulation and the like.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances and a preparation method thereof, and the purpose of anticoagulation, antibiosis and fouling resistance on the surface of a blood contact instrument is realized based on the good blood compatibility, the impedance protein adsorption function and the sterilization effect of an antibacterial agent of a zwitter-ion-containing hydrogel.

In order to achieve the purpose, the technical scheme adopted by the invention for solving the technical problems is as follows: the preparation method of the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances is provided, and comprises the following steps in sequence:

(1) cleaning the substrate material, and then fixing an initiator;

(2) under the condition of illumination, reacting a zwitterionic monomer with a monomer containing double bonds and carboxyl for 1-3h, and cleaning to obtain a medical coating;

(3) and (3) placing the medical coating obtained in the step (2) in an acid environment, activating by using the mixed solution, adding an antibacterial agent to react for 24 hours, and then sequentially cleaning and drying to obtain the biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances.

The technical scheme is as follows:

(1) the substrate material is cleaned and then the initiator is fixed.

(2) In the reaction system, the concentration of the zwitterionic monomer is in the range of 2.5 wt% to 15.0 wt%, and the concentration of the monomer having a double bond and a carboxyl group is in the range of 5.0 wt% to 25.0 wt%. Under the condition of ultraviolet illumination, the two monomers undergo in-situ polymerization for 1 to 3 hours to obtain a medical coating, and after the reaction is finished, the surface is cleaned by deionized water for 2 to 3 days to remove the residual unreacted monomers. Wherein the zwitterion can be three main types of ammonium phosphate, ammonium sulfonate and ammonium carboxylate.

(3) Placing the prepared coating in an acid environment (the pH range is 5.0-6.0), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding an antibacterial agent into a solution system, wherein the concentration of the antibacterial agent can be 1-10mg/mL, and reacting for 24 hours. Among them, antibiotics which can be used for grafting are various, and antibiotics, antibacterial peptides having different combinations of amino acid sequences, and the like can be used.

(4) Cleaning the prepared coating for 3 times, each time for 15min, and then drying under the condition of nitrogen to obtain the coating.

Further, the substrate material is a polymer-based biomaterial or a polymer-based composite biomaterial.

Further, the polymer-based biomaterial is polyvinyl chloride, polyurethane, polylactic acid or polyvinylpyrrolidone.

Further, the initiator is a monomer containing a halogen bond, benzophenone or azobisisobutyronitrile.

Further, the zwitterion is 2- (methacryloyloxy) ethyl-2- (trimethylamino) ethyl phosphate, [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide, or 3- [ [2- (methacryloyloxy) ethyl ] dimethyl ammonium ] propionate.

Further, the monomer containing a double bond and a carboxyl group is methacrylic acid.

Further, the mixed solution is a mixture of 0.1 to 0.5M of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 0.05 to 0.2M of N-hydroxysuccinimide ester.

Further, the antibacterial agent is antibiotic or antibacterial peptide, and the concentration is 1-10 mg/mL.

Further, the concentration of the zwitterionic monomer is 2.5-15 wt%, and the concentration of the monomer containing double bonds and carboxyl groups is 5-25 wt%.

Further, in the step (3), the mixture is washed for 2 to 4 times, each time for 10 to 20min, and dried under the condition of nitrogen.

The biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance prepared by the preparation method of the biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance.

In summary, the invention has the following advantages:

1. the invention realizes the purposes of anticoagulation, antibiosis and stain resistance on the surface of a blood contact apparatus based on the good blood compatibility, the protein-resistant adsorption function and the sterilization function of an antibacterial agent of the hydrogel containing zwitterion. The preparation process has mild reaction conditions and simple operation. The initiator is introduced into the surface of the material in situ, and the crosslinking is initiated in situ under the irradiation of ultraviolet light to form a uniform hydrogel coating. The prepared hydrogel coating has excellent stability and can not be degraded after being soaked in simulated body fluid for one month.

2. The hydrogel coating contains zwitterions, so that a 'hydration layer' is formed on the surface of the coating by free water, and the hydrogel coating has the characteristics of anti-fouling and anticoagulation, can effectively resist nonspecific protein adhesion, and can further resist the adhesion of protein and cells in blood and the adhesion of bacteria. The introduction of the antibacterial agent enables the coating to have excellent bactericidal performance, and the type of the introduced antibacterial agent can be antibiotics, antibacterial peptides and the like. The hydrogel coating shields the cytotoxicity of the antibacterial agent, well protects the activity of the antibacterial agent and enables the coating to have a long-acting antibacterial effect.

3. The initiator can be fixed on the surface of the material in a physical deposition or immersion mode, and under the condition of ultraviolet irradiation initiation, free radicals are generated to open the double bonds of the two monomers and generate a crosslinking reaction, so that a hydrogel coating is formed on the surface of the material in situ. The unreacted monomer is then removed by prolonged washing. After cleaning, the hydrogel coating was soaked in 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS) to activate surface carboxyl groups. The activated carboxyl is combined with the antibacterial agent, so that the antibacterial agent is combined on the surface of the hydrogel coating, and meanwhile, the coating is endowed with excellent bactericidal capacity. The hydrogel coating contains a large amount of zwitterions, so that the hydrogel coating has anticoagulation and anti-fouling effects. The killed bacteria can not be adhered to the surface of the coating, so that the antibacterial efficiency of the coating can not be reduced due to the accumulation of the bacteria, and in addition, the hydrogel coating protects the antibacterial agent and ensures the long-term stable antibacterial action. The zwitterion can effectively resist nonspecific protein adsorption, so that the medical coating prepared from the zwitterion can resist protein and cell adsorption in blood, and has good blood compatibility. In conclusion, the preparation method disclosed by the invention is simple to operate, the reaction conditions are mild, and the prepared coating has excellent sterilization and anti-fouling performance and blood compatibility, and provides a new idea for the antibacterial, anticoagulant and anti-fouling of a blood contact medical instrument.

4. In order to realize the dual functions of antibiosis and antithrombotic, improve the stability of the antibacterial agent and reduce the negative effect of cationic property, the invention provides an antibacterial agent-hydrogel coating embedding strategy. The embedded antibacterial agent enables the hydrogel coating to have antibacterial performance and keeps good anticoagulation and anti-fouling performance of the hydrogel coating. In this study, we chose a surface-initiated polymerization method to form a thin coating on a polymeric substrate, with acids with double bonds and zwitterions as monomers to initiate polymerization. Two different antibacterial agents are embedded into the hydrogel coating layer by adopting a physical adsorption and chemical grafting method so as to achieve the effects of anticoagulation, antibiosis and stain resistance.

5. The method is simple to operate, the reaction condition is mild, the prepared coating is firmly combined with the substrate material, and the coating simultaneously contains the zwitterionic polymer and the antibacterial agent. The zwitterion has the effects of anticoagulation and stain resistance, the hydrogel coating obtained by polymerization of the zwitterion has the protection effect on an antibacterial agent, and the cytotoxicity of the antibacterial agent is shielded, so that the material has the long-term antibacterial and stain resistance effect and also has good blood compatibility, and can be used for the anticoagulation and antibacterial application modification requirements of blood contact materials/instruments such as an extracorporeal membrane oxygenation (ECMO) circulation pipeline, a central venous catheter, a dialysis pipeline for heart failure resistance treatment, an indwelling needle and the like.

Drawings

FIG. 1 is a scanning electron microscope picture of the biomedical coating with excellent long-acting anticoagulation and antibacterial anti-fouling performance in example 1 after the biomedical coating contacts with platelets on the surface of an uncoated polytetrafluoroethylene material;

FIG. 2 is a picture of the coated plate for cloning and nutrition-enriched culture with excellent long-acting anticoagulant, antibacterial and anti-fouling performance of the biomedical coating and the surface antibacterial property of the uncoated polytetrafluoroethylene material in example 1.

Detailed Description

Example 1

A biomedical coating with excellent long-acting anticoagulation and antibacterial and anti-fouling performances is prepared by the following steps in sequence:

(1) cleaning a polyvinyl chloride conduit, and then pouring benzophenone into the polyvinyl chloride conduit for fixing;

(2) pouring a zwitterionic monomer 2- (methacryloyloxy) ethyl-2- (trimethyl amino) ethyl phosphate (MPC) and a monomer methacrylic acid (AAc) with double bonds and carboxyl into a polyvinyl chloride conduit, wherein the ratio of the two monomers is 3:7, carrying out in-situ polymerization under ultraviolet irradiation for 1 hour to obtain a hydrogel coating, and after the reaction is finished, cleaning the surface with deionized water for 2-3 days to remove residual unreacted 2- (methacryloyloxy) ethyl-2- (trimethyl amino) ethyl phosphate (MPC) and the methacrylic acid (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 4.0), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of WRWRWRWRWRWRWRWRWRWRWR-NH 2) into a solution system, and reacting for 24 hours to obtain the hydrogel-embedded antibacterial peptide coating; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 2

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning a polylactic acid material, then immersing the polylactic acid material into a benzophenone solution, and fixing an initiator;

(2) spreading mixed solution of zwitterionic monomer 2- (methacryloyloxy) ethyl-2- (trimethyl amino) ethyl phosphate (MPC) and monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of a polylactic acid material, wherein the ratio of the two monomers is 3:7, carrying out in-situ polymerization under ultraviolet irradiation for 1.5 hours to obtain a hydrogel coating, and cleaning the surface with deionized water for 2-3 days after the reaction is finished to remove residual unreacted 2- (methacryloyloxy) ethyl-2- (trimethyl amino) ethyl phosphate (MPC) and methacrylic acid (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 5.5), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of WRWRWRWRWRWRWRWRWRWRWR-NH 2) into a solution system, and reacting for 24 hours to obtain the hydrogel-embedded antibacterial peptide coating; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 3

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning a polyurethane material, then immersing the polyurethane material into an azodicarbonitrile solution, and fixing an initiator;

(2) spreading mixed solution of a zwitterionic monomer [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and a monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of a polyurethane material, wherein the ratio of the two monomers is 2:3, carrying out in-situ polymerization under ultraviolet irradiation for 2 hours to obtain a hydrogel coating, and cleaning the surface with deionized water for 2-3 days after the reaction is finished to remove residual unreacted 2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and the methacrylic acid monomer (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 5.0), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of RLARIVVIRVAR-NH2) into a solution system, reacting for 24 hours, and thus obtaining the antibacterial peptide coating embedded in the hydrogel; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 4

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning a polyurethane material, then immersing the polyurethane material into an azodicarbonitrile solution, and fixing an initiator;

(2) spreading mixed solution of a zwitterionic monomer [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and a monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of a stainless steel material, wherein the ratio of the two monomers is 2:3, carrying out in-situ polymerization under the irradiation of ultraviolet light, wherein the reaction time is 3 hours to obtain a hydrogel coating, and after the reaction is finished, cleaning the surface with deionized water for 2-3 days to remove residual unreacted [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and the methacrylic acid monomer (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 5.5), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of RLARIVVIRVAR-NH2) into a solution system, reacting for 24 hours, and thus obtaining the hydrogel-embedded antibacterial peptide coating; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 5

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning a ceramic material, immersing the ceramic material in a benzophenone solution, and fixing an initiator;

(2) spreading mixed solution of a zwitterionic monomer [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and a monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of the ceramic material, wherein the ratio of the two monomers is 1:3, carrying out in-situ polymerization under the irradiation of ultraviolet light, wherein the reaction time is 1 hour, so as to obtain a hydrogel coating, and cleaning the surface with deionized water for 2-3 days after the reaction is finished so as to remove residual unreacted [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA) and the methacrylic acid monomer (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 6.0), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of WRWRWRWRWRWRWRWRWRWRWR-NH 2) into a solution system, and reacting for 24 hours to obtain the hydrogel-embedded antibacterial peptide coating; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 6

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning a medical collagen material, immersing the medical collagen material into a benzophenone solution, and fixing an initiator;

(2) spreading mixed solution of zwitterionic monomer 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate (CBMA) and monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of the medical collagen material, wherein the ratio of the two monomers is 3:7, carrying out in-situ polymerization under the irradiation of ultraviolet light, wherein the reaction time is 1 hour, obtaining a hydrogel coating, and cleaning the surface with deionized water for 2-3 days after the reaction is finished to remove residual unreacted 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate (CBMA) and methacrylic acid monomer (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 5.5), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of WRWRWRWRWRWRWRWRWRWRWR-NH 2) into a solution system, and reacting for 24 hours to obtain the hydrogel-embedded antibacterial peptide coating; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

Example 7

A biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-pollution performance and a preparation method thereof are disclosed, the preparation method comprises the following steps:

(1) cleaning the titanium alloy material reinforced by the bioactive glass ceramic coating, then immersing the titanium alloy material into an azodicarbonitrile butadiene-acrylonitrile solution, and fixing an initiator;

(2) spreading mixed solution of zwitterionic monomer 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate (CBMA) and monomer methacrylic acid (AAc) with double bonds and carboxyl on the surface of the titanium alloy material reinforced by the bioactive glass ceramic coating, wherein the ratio of the two monomers is 2:3, carrying out in-situ polymerization under the irradiation of ultraviolet light for 1.5 hours to obtain a hydrogel coating, and cleaning the surface with deionized water for 2-3 days to remove residual unreacted 3- [ [2- (methacryloyloxy) ethyl ] dimethylammonium ] propionate (CBMA) and methacrylic acid monomer (AAc);

(3) placing the prepared hydrogel coating in an acidic environment (pH is 5.0), activating surface carboxyl by using 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester (NHS), adding antibacterial peptide (with the sequence of RLARIVVIRVAR-NH2) into a solution system, reacting for 24 hours, and thus obtaining the antibacterial peptide coating embedded in the hydrogel; and (3) washing with deionized water for 15 minutes each time, and then drying under the condition of nitrogen to obtain the biomedical coating with excellent long-acting anticoagulation, antibiosis and anti-fouling performances.

The number of platelets adhered and activated on the surface of the material with hydrogel embedded antimicrobial peptide coating was significantly reduced compared to uncoated polyvinyl chloride, and the results are shown in fig. 1. In an antibacterial experiment, the antibacterial peptide coating embedded in the hydrogel also shows better antibacterial performance, the sterilization rate can reach 100%, and the result is shown in fig. 2.

The coating prepared by the method is uniform and stable in property, the raw material investment required for preparing the coating is small, the investment amount is easy to regulate and control, the coating can be modified on the surfaces of various materials without influencing the performance of the body material, the operation is simple, the cost is low, and the method is suitable for industrial production.

While the present invention has been described in detail with reference to the illustrated embodiments, it should not be construed as limited to the scope of the present patent. Various modifications and changes may be made by those skilled in the art without inventive step within the scope of the appended claims.