A method and application of preparing antibacterial osteogenic film by chemical vapor deposition technology

Abstract

The present invention provides a method for preparing an antibacterial osteogenic film by chemical vapor deposition technology, wherein the initiator di-tert-butyl peroxide, the first functional monomer 2-(dimethylamino)ethyl methacrylate, the second functional monomer methacrylic acid, and the cross-linking agent ethylene glycol diacrylate are heated and gasified respectively and flow into a chemical vapor deposition reactor, and the first film is deposited on a substrate by the cross-linking action of the cross-linking agent to form a first film; when the thickness of the first film reaches the expected requirement by monitoring, the cross-linking agent is stopped; under the action of the initiator, the first functional monomer and the second functional monomer continue polymerization reaction, and the second film is deposited on the first film to form a second film, and when the second film reaches the expected thickness by monitoring, the first functional monomer, the second functional monomer and the initiator are stopped; and an antibacterial adhesion osteogenic polymer film is obtained. The antibacterial adhesion osteogenic polymer film prepared by the present invention has strong antibacterial adhesion ability and good osteogenic effect, and has broad application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of material preparation, and in particular to a method and application of preparing an antibacterial osteogenic film using a chemical vapor deposition technique. Background Art

[0002] With the development of medical technology and the widespread use of medical devices, the compatibility of devices with the human body has become the key to the long-term safety of devices. Biomedical coatings play a vital role in improving the biocompatibility of implantable medical devices. They can also give materials and devices new therapeutic functions and reduce the occurrence of complications. For example, the emergence of drug-eluting stents and balloon systems with anti-proliferative capabilities has greatly reduced the problem of restenosis after surgery with traditional bare stents and bare balloons, thus significantly improving the postoperative efficacy of patients.

[0003] Bone implants are always threatened by conditional pathogens during and after implantation. Bacterial adhesion and subsequent biofilm formation on the surface of bone implants are the main reasons for the failure of bone implant implantation. Modifying the surface of bone implants with a dual-functional film with antibacterial adhesion and osteogenesis to prepare new bone repair materials is a new direction for the development of bone implant materials. The hydration layer formed by the ionic bond of amphoteric polyelectrolytes can effectively prevent the adhesion of bacteria on their surface. At the same time, amphoteric polyelectrolytes promote osteogenesis through the properties of the groups they carry.

[0004] Prior art CN113842507A discloses a polyelectrolyte hydrogel coating with super strong substrate adhesion performance and a preparation method thereof. The preparation method comprises dissolving a polycationic polymer, a polymerizing monomer, a siloxane crosslinking agent and an initiator to obtain a prepolymer solution, vacuuming to remove bubbles and then coating the solution on the surface of a substrate activated by oxygen plasma, in-situ polymerizing under a nitrogen or rare gas atmosphere, curing and the like. The polyelectrolyte hydrogel coating formed thereby has good biocompatibility and controllable mechanical properties. However, the preparation method thereof is too complicated, requiring the preparation of a prepolymer solution first and then vacuuming, coating, in-situ polymerization, curing and the like. The substrate also needs to be activated in advance, and the operation steps are complicated. Moreover, the polyelectrolyte hydrogel coating has only a single polycationic polymer and cannot provide sufficient antibacterial function. Pathogenic bacteria are still easy to multiply on the surface of bone implants to form biofilms, causing human wound infections. Summary of the invention

[0005] In order to solve the technical problems of poor antibacterial property, poor osteogenesis promoting ability and complicated preparation steps of modified films on the surface of traditional bone implants, the purpose of the present invention is to provide a method and application of preparing antibacterial osteogenic films using chemical vapor deposition technology. The present invention expands the application of antibacterial adhesion osteogenic polymer films in the field of bone surface regeneration materials.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions.

[0007] The present invention provides a method for preparing an antibacterial osteogenic film using a chemical vapor deposition technique, comprising:

[0008] Arranging the nickel-chromium wire above the reaction table and heating it to a predetermined temperature;

[0009] The initiator di-tert-butyl peroxide, the first functional monomer 2-(dimethylamino)ethyl methacrylate, the second functional monomer methacrylic acid, and the cross-linking agent ethylene glycol diacrylate are heated and vaporized respectively and then flow into a chemical vapor deposition reactor, and deposited on a substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches the expected requirement by monitoring, the flow of the cross-linking agent is stopped;

[0010] The first functional monomer and the second functional monomer continue to polymerize under the action of the initiator to form a second film deposited on the first film, and when the second film reaches a desired thickness by monitoring, the first functional monomer, the second functional monomer and the initiator are stopped from flowing;

[0011] The residues of the first film and the second film prepared on the substrate are removed to obtain an antibacterial adhesion bone-promoting polymer film.

[0012] As a further improvement of the present invention, the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent is (1-10):(1-10):(1-5).

[0013] As a further improvement of the present invention, the chemical vapor deposition reactor controls the pressure to 0.1-1.0 Torr through a throttle valve, and controls the flow rate through a mass flow controller.

[0014] As a further improvement of the present invention, the initiator di-tert-butyl peroxide is heated to 10-30°C, the first functional monomer 2-(dimethylamino)ethyl methacrylate is heated to 40-70°C, the second functional monomer methacrylic acid is heated to 40-60°C, and the crosslinking agent ethylene glycol diacrylate is heated to 45-60°C.

[0015] As a further improvement of the present invention, the expected thickness of the first film is 100-800 nm; the expected thickness of the second film is 100-200 nm;

[0016] The thickness of the first film and the second film are monitored by real-time laser interferometry.

[0017] As a further improvement of the present invention, during the process of depositing the first thin film and the second thin film, the temperature of the substrate is controlled to be 30-60° C. by a water circulation system, and the temperature of the substrate is monitored by a thermocouple.

[0018] As a further improvement of the present invention, the nickel-chromium wire is arranged 2.5-3 cm above the reaction table, and the predetermined heating temperature of the nickel-chromium wire is 200-400°C.

[0019] As a further improvement of the present invention, the substrate is one of a plastic sheet, a titanium sheet, a basic calcium phosphate support or a silicon sheet.

[0020] As a further improvement of the present invention, the antibacterial adhesion and bone-promoting polymer film is a double-layer polymer film P(DMAEMA-co-MAA-co-EGDA)-gP(DMAEMA-co-MAA), wherein the first film of the bottom layer is P(DMAEMA-co-MAA-co-EGDA) and the second film of the upper layer is P(DMAEMA-co-MAA).

[0021] Application of the antibacterial adhesion bone-promoting polymer film obtained by the preparation method of the present invention on the surface of bone regeneration materials.

[0022] Compared with the prior art, the present invention has the following advantages:

[0023] The present invention controls the deposition of the first film and the second film on the substrate after the reactants are vaporized by an induced chemical vapor deposition method. The deposition and film formation process can be realized by controlling the chemical vapor deposition reactor. The preparation method has simple operation steps, and the obtained antibacterial adhesion and bone-promoting polymer film has good antibacterial ability and bone-promoting ability. The double-layer polymer film P (DMAEMA-co-MAA-co-EGDA)-gP (DMAEMA-co-MAA) has good biocompatibility, osteoconductivity and osteoinductivity, which can further expand the application of antibacterial adhesion and bone-promoting polymer films in the field of bone surface regeneration materials. The preparation method of the antibacterial adhesion and bone-promoting polymer film provided by the present invention is simple and efficient to operate, and the reaction conditions are mild. The obtained antibacterial adhesion and bone-promoting polymer film has strong antibacterial adhesion ability and good bone-promoting effect, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a schematic diagram of the structure of the antibacterial adhesion bone-promoting polymer film provided in a specific embodiment of the present invention;

[0025] Figure 2 The SEM image and FT-IR spectrum of the antibacterial adhesion and osteogenic polymer film modified basic calcium phosphate bone scaffold provided in Example 1 of the specific embodiment of the present invention;

[0026] Figure 3 This is a fluorescence micrograph of the antibacterial adhesion of a plastic sheet modified with an antibacterial adhesion and bone-promoting polymer film provided in Example 2 of a specific embodiment of the present invention;

[0027] Figure 4 This is a SEM image of the osteoconductivity of the basic calcium phosphate bone scaffold and the antibacterial adhesion osteopromoting polymer film modified basic calcium phosphate bone scaffold provided in Example 5 of the specific embodiment of the present invention;

[0028] Figure 5 This is a comparison chart of the biocompatibility and osteoinductivity test results of the basic calcium phosphate bone scaffold and the antibacterial adhesion osteopromoting polymer film modified basic calcium phosphate bone scaffold provided in Example 1 of the specific embodiment of the present invention. DETAILED DESCRIPTION

[0029] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described below through embodiments.

[0030] It should be understood that the terms described in the present invention are only embodiments for describing features and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0031] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods or materials related to the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0032] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present application description and examples are exemplary only.

[0033] The present invention provides a method for preparing an antibacterial osteogenic film using a chemical vapor deposition technique, comprising the following steps:

[0034] S1. placing a substrate on a sample stage of a chemical vapor deposition reactor; arranging a nickel-chromium wire above the reaction stage and heating it to a predetermined temperature;

[0035] S2, heating the initiator di-tert-butyl peroxide, the first functional monomer 2-(dimethylamino)ethyl methacrylate, the second functional monomer methacrylic acid, and the cross-linking agent ethylene glycol diacrylate respectively to make them gaseous and then flow into the reactor, and deposit them on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches the expected requirement by monitoring, stopping the flow of the cross-linking agent;

[0036] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator to form a second film deposited on the first film, and when the second film reaches a desired thickness by monitoring, the first functional monomer, the second functional monomer and the initiator are stopped from flowing;

[0037] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0038] Compared with the prior art, the present invention forms the first film and the second film by polymer chemical vapor deposition. The preparation method combines the traditional liquid phase free radical polymerization reaction with chemical vapor deposition technology, and introduces the initiator, cross-linking agent and functional monomer required for polymerization into the reaction chamber after being vaporized, and induces the initiator to decompose and generate free radicals at a relatively low heating temperature, so that the first functional monomer and the second functional monomer undergo polymerization reaction through free radicals and synthesize the first film that is tightly attached to the substrate under the cross-linking action of the cross-linking agent; after the inflow of the cross-linking agent is stopped, the initiator continues to be heated and decomposed by the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the functional monomers, and the synthesized polymer is deposited on the first film to form the second film; in addition, due to the polymer chemical vapor deposition The reaction conditions of the deposition are mild. Compared with the fierce reaction conditions of plasma chemical vapor deposition, it does not damage the film and can keep the functional groups of the antibacterial adhesion and osteopromoting polymer film unaffected. Moreover, the polymer chemical vapor deposition reaction process does not use organic solvents that are harmful to the human body. The obtained antibacterial adhesion and osteopromoting polymer film is an amphoteric polyelectrolyte film. The positive and negative charges are combined with water molecules through ionic bonds, so that the polymer forms a hydration layer. The hydration layer acts as a physical protective layer to prevent bacteria from adhering to the surface of the film to form a biofilm, which has a good antibacterial effect. The amphoteric polyelectrolyte film also has rich and dense functional groups, which can promote the differentiation of preosteoblasts, so that the antibacterial adhesion and osteopromoting polymer film has a significant osteopromoting effect.

[0039] Preferably, in step S2, the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent is (1-10): (1-10): (1:5). The chemical vapor deposition reactor controls the pressure to 0.1-1.0 Torr through a throttle valve, and controls the flow rate through a mass flow controller. Reasonable regulation of the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent is conducive to controlling the usage ratio of each reactant, ensuring that the obtained antibacterial adhesion osteogenic polymer film has a good osteogenic effect.

[0040] Preferably, in step S2, the initiator di-tert-butyl peroxide is heated to 10-30° C., the first functional monomer 2-(dimethylamino)ethyl methacrylate is heated to 40-70° C., the second functional monomer methacrylic acid is heated to 40-60° C., and the crosslinking agent ethylene glycol diacrylate is heated to 45-60° C. The temperature of each reactant is controlled within a certain temperature range to control the vaporization rate, thereby controlling the deposition rate, and controlling the reaction time to control the thickness of the film.

[0041] Preferably, in step S2, the expected thickness of the first film is 100-800 nm; in step S3, the expected thickness of the second film is 100-200 nm; the chemical vapor deposition process monitors the thickness of the first film and the second film by a real-time laser interferometer. The use of a real-time laser interferometer to monitor the formation thickness of the first film and the second film can accurately control the micro-nano scale of the film.

[0042] Preferably, in step S1, the nickel-chromium wire is arranged 2.5-3 cm above the reaction table, and the predetermined heating temperature of the nickel-chromium wire is 200-400° C. The nickel-chromium wire is arranged above the reaction table and heated to a predetermined temperature, so that the initiator can be heated and decomposed by the nickel-chromium wire after entering the reactor to generate free radicals, thereby initiating a free radical chain polymerization reaction between the monomers.

[0043] The antibacterial adhesion and osteogenic polymer film provided by the present invention is an amphoteric polyelectrolyte film with antibacterial adhesion and osteogenic capabilities, which can effectively resist bacteria and promote bone formation, and effectively improve the osteogenic capacity of bone implants.

[0044] The invention provides an application of the antibacterial adhesion bone-promoting polymer film on the surface of bone regeneration materials.

[0045] Specifically, an embodiment of the present invention discloses a method for preparing an antibacterial osteogenic film using chemical vapor deposition technology, comprising the following steps:

[0046] S1. Place a substrate on a sample stage of a chemical vapor deposition reactor. The substrate is selected from a plastic sheet, a titanium sheet, a basic calcium phosphate support or a silicon sheet. The substrate temperature is controlled at 30-60°C by a water circulation system and a thermocouple. Arrange a nickel-chromium wire 2.5-3 cm above the reaction stage and heat it to 200-400°C.

[0047] S2, respectively heating the initiator di-tert-butyl peroxide (TBP) to 10-30° C., the first functional monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA) to 40-70° C., the second functional monomer methacrylic acid (MAA) to 40-60° C., and the crosslinking agent ethylene glycol diacrylate (EGDA) to 45-60° C., and gasifying the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent and then flowing them into the reactor respectively;

[0048] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be (1-10):(1-10):(1:5), and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.1-1.0 Torr by adjusting the throttle valve;

[0049] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 100-800 nm through real-time laser interferometer monitoring, the flow of the cross-linking agent is stopped;

[0050] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100-200nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0051] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0052] Combination Figure 1As shown, this specific embodiment uses an initiated chemical vapor deposition method to synthesize a multi-component amphoteric polyelectrolyte film on a bone implant substrate, namely, an antibacterial adhesion and bone-promoting polymer film P (DMAEMA-co-MAA-co-EGDA)-gP (DMAEMA-co-MAA). The present invention combines traditional liquid-phase free radical polymerization with chemical vapor deposition technology, and allows functional monomers to generate a polymer film with high adhesion and high antibacterial adhesion ability through free radical polymerization under mild reaction conditions; the deposition film formation process uses laser monitoring to accurately control the film thickness, and the micro-nano film can be evenly plated on the substrate surface; the preparation method of the antibacterial adhesion and bone-promoting polymer film provided by this specific embodiment is simple and efficient, and the reaction conditions are mild. The obtained antibacterial adhesion and bone-promoting polymer film has good antibacterial adhesion and bone-promoting effect, is not easy to breed bacterial capsules, and further improves the success rate of bone implants.

[0053] The present invention is further described with reference to the following embodiments:

[0054] Example 1

[0055] S1. Place the basic calcium phosphate support substrate on the sample stage of the chemical vapor deposition reactor, and control the substrate temperature to 31° C. through the water circulation system control and thermocouple monitoring; arrange the nickel-chromium wire 2.5 cm above the reaction table and heat it to 220° C.;

[0056] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 20° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 60° C., heating the second functional monomer methacrylic acid to 55° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0057] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 4:8:3, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.35 Torr by adjusting the throttle valve;

[0058] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 200 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0059] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0060] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0061] Combination Figure 2 As shown, Figure 2 Compared with the surface of the basic calcium phosphate bone scaffold in the middle A, the antibacterial adhesion and osteogenic polymer film can Figure 2 As shown in B, it is very evenly coated on the surface of the bone scaffold; Figure 2 Figure C shows that after modification with the antibacterial adhesion and osteogenic polymer film, the FT-IR spectrum shows characteristic peaks of C=O and OH, proving that the antibacterial adhesion and osteogenic polymer film is successfully coated on the surface of the basic calcium phosphate bone scaffold.

[0062] Combination Figure 5 As shown, a represents a basic calcium phosphate bone scaffold, and b represents a basic calcium phosphate bone scaffold modified with an antibacterial adhesion bone-promoting polymer film. Figure 5 The experimental results of MTT cell proliferation and cytotoxicity assays in Figure A showed that the bone scaffold modified with antimicrobial adhesion-promoting osteogenic polymer film had similar cell activity to the base bone scaffold, so it had good biocompatibility; Figure 5 ALP (alkaline phosphatase) and Figure 5 The OCN (osteocalcin) activity in C indicated that the bone scaffolds modified with antimicrobial adhesion osteogenic polymer film had better osteoinductivity than the base bone scaffolds.

[0063] Example 2

[0064] S1. Place a plastic substrate on a sample stage of a chemical vapor deposition reactor, and control the substrate temperature to 31° C. by controlling the water circulation system and monitoring the substrate temperature with a thermocouple; arrange a nickel-chromium wire 2.5 cm above the reaction stage and heat it to 220° C.;

[0065] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 20° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 60° C., heating the second functional monomer methacrylic acid to 55° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0066] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 2:1:1, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.35 Torr by adjusting the throttle valve;

[0067] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 200 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0068] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0069] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0070] Combination Figure 3 As shown, Figure 3a is a fluorescence micrograph of antibacterial adhesion of plastic sheets, Figure 3 Middle b is the antibacterial adhesion fluorescence micrograph of the plastic sheet modified with the antibacterial adhesion and bone-promoting polymer film. It can be seen that the number of bacteria on the surface of the antibacterial adhesion and bone-promoting polymer film is significantly reduced, showing a strong antibacterial adhesion ability.

[0071] Example 3

[0072] S1. Place the basic calcium phosphate bone scaffold substrate on the sample stage of the chemical vapor deposition reactor, and control the substrate temperature at 30° C. through the water circulation system control and thermocouple monitoring; arrange the nickel-chromium wire 3 cm above the reaction table and heat it to 400° C.;

[0073] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 15° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 40° C., heating the second functional monomer methacrylic acid to 60° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0074] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 1:10:3, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.1 Torr by adjusting the throttle valve;

[0075] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 800 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0076] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 200nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0077] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0078] Example 4

[0079] S1. Place the basic calcium phosphate support substrate on the sample stage of the chemical vapor deposition reactor, and control the substrate temperature at 60° C. through the water circulation system control and thermocouple monitoring; arrange the nickel-chromium wire 2.5 cm above the reaction table and heat it to 200° C.;

[0080] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 10° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 70° C., heating the second functional monomer methacrylic acid to 40° C., and heating the crosslinking agent ethylene glycol diacrylate to 60° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0081] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 10:1:5, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.4 Torr by adjusting the throttle valve;

[0082] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 100 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0083] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0084] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0085] Example 5

[0086] S1. Place the basic calcium phosphate bone scaffold substrate on the sample stage of the chemical vapor deposition reactor, and control the substrate temperature to 40° C. through the water circulation system control and thermocouple monitoring; arrange the nickel-chromium wire 2.5 cm above the reaction table and heat it to 280° C.;

[0087] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 30° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 55° C., heating the second functional monomer methacrylic acid to 55° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0088] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 3:3:2, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.5 Torr by adjusting the throttle valve;

[0089] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 500 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0090] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0091] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0092] Combination Figure 4 As shown, Figure 4 In the middle, a is a basic calcium phosphate bone scaffold. Figure 4 Middle b is a basic calcium phosphate bone scaffold modified with an antibacterial adhesion and osteogenic polymer film. Figure 4 The results showed that the bone conductivity of B was good, and mouse preosteoblasts could grow well on the surface of the bone scaffold modified by the antibacterial adhesion osteogenic polymer film.

[0093] Example 6

[0094] S1. Place a silicon wafer substrate on a sample stage of a chemical vapor deposition reactor, and control the substrate temperature to 40° C. through a water circulation system and thermocouple monitoring; arrange a nickel-chromium wire 2.5 cm above the reaction stage and heat it to 200° C.;

[0095] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 30° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 50° C., heating the second functional monomer methacrylic acid to 45° C., and heating the crosslinking agent ethylene glycol diacrylate to 45° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0096] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 1:1:1, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 0.25 Torr by adjusting the throttle valve;

[0097] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 600 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0098] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 150nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0099] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0100] Example 7

[0101] S1. Place a silicon wafer substrate on a sample stage of a chemical vapor deposition reactor, and control the substrate temperature at 35° C. through a water circulation system and thermocouple monitoring; arrange a nickel-chromium wire 3 cm above the reaction stage and heat it to 400° C.;

[0102] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 25° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 60° C., heating the second functional monomer methacrylic acid to 58° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0103] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 8:8:5, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 1 Torr by adjusting the throttle valve;

[0104] The polymerized product is deposited on the substrate to form a first film through the cross-linking action of the cross-linking agent; when the thickness of the first film reaches 700 nm, the flow of the cross-linking agent is stopped by monitoring the real-time laser interferometer;

[0105] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator, and deposit on the first film to form a second film to increase the functional group density of the surface layer of the antibacterial adhesion and bone-promoting polymer film, and when the second film reaches 100nm through real-time laser interferometer monitoring, stop the flow of the first functional monomer, the second functional monomer and the initiator;

[0106] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0107] Example 8

[0108] S1. Place a titanium substrate on a sample stage of a chemical vapor deposition reactor, and control the substrate temperature to 50° C. by controlling the water circulation system and monitoring the substrate temperature with a thermocouple; arrange a nickel-chromium wire 2.5 cm above the reaction stage and heat it to 300° C.;

[0109] S2, respectively controlling the temperature of the initiator di-tert-butyl peroxide to 28° C., heating the first functional monomer 2-(dimethylamino)ethyl methacrylate to 68° C., heating the second functional monomer methacrylic acid to 55° C., and heating the crosslinking agent ethylene glycol diacrylate to 55° C., so that the initiator, the first functional monomer, the second functional monomer, and the crosslinking agent are gasified and flow into the reactor respectively;

[0110] The mass flow controller is used to control the flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent to be 2:6:4, and the initiator is allowed to enter the reactor and decomposed by heating with the nickel-chromium wire to generate free radicals, thereby initiating a free radical chain polymerization reaction between the first functional monomer and the second functional monomer; the pressure of the reactor is controlled to be 1 Torr by adjusting the throttle valve;

[0111] The polymerized product is deposited on the substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches 750nm through real-time laser interferometer monitoring, the flow of the cross-linking agent is stopped;

[0112] S3, the first functional monomer and the second functional monomer continue to polymerize under the action of the initiator to form a second thin film deposited on the first thin film, and when the second thin film reaches 160nm through real-time laser interferometer monitoring, the first functional monomer, the second functional monomer and the initiator are stopped from flowing;

[0113] S4. After the reaction is completed, the sample prepared on the substrate is washed with water to remove the residue, and then dried to obtain an antibacterial adhesion bone-promoting polymer film.

[0114] Although the disclosure is disclosed as above, the protection scope of the disclosure is not limited thereto. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the disclosure, and these changes and modifications will fall within the protection scope of the present invention.

[0115] All articles and references disclosed above, including patent applications and publications, are incorporated herein by reference for all purposes. The term "consisting essentially of..." describing a combination should include the identified elements, ingredients, parts or steps and other elements, ingredients, parts or steps that do not substantially affect the basic novel features of the combination. The use of the terms "comprising" or "including" to describe the combination of elements, ingredients, parts or steps herein also contemplates embodiments that are essentially composed of these elements, ingredients, parts or steps. By using the term "may", it is intended to illustrate that any attribute described that "may" include is optional.

[0116] It should be understood that the above description is for illustration and not for limitation. Many embodiments and many applications beyond the examples provided will be apparent to those skilled in the art upon reading the above description. Therefore, the scope of the present teachings should not be determined with reference to the above description, but rather with reference to the foregoing claims and the full scope of equivalents to which such claims are entitled. For the purpose of comprehensiveness, all articles and references, including disclosures of patent applications and publications, are incorporated herein by reference. The omission of any aspect of the subject matter disclosed herein in the foregoing claims is not intended to be a waiver of such subject matter, nor should it be considered that the applicant has not considered such subject matter to be part of the disclosed inventive subject matter.

Claims

1. A method for preparing an antibacterial osteogenic film using chemical vapor deposition technology, characterized in that: include: Arranging the nickel-chromium wire above the reaction table and heating it to a predetermined temperature; The initiator di-tert-butyl peroxide, the first functional monomer 2-(dimethylamino)ethyl methacrylate, the second functional monomer methacrylic acid, and the cross-linking agent ethylene glycol diacrylate are heated and vaporized respectively and then flow into a chemical vapor deposition reactor, and deposited on a substrate to form a first film through the cross-linking effect of the cross-linking agent; when the thickness of the first film reaches the expected requirement by monitoring, the flow of the cross-linking agent is stopped; The first functional monomer and the second functional monomer continue to polymerize under the action of the initiator to form a second film deposited on the first film, and when the second film reaches a desired thickness by monitoring, the first functional monomer, the second functional monomer and the initiator are stopped from flowing; removing residues from the first film and the second film prepared on the substrate to obtain an antibacterial adhesion bone-promoting polymer film; The flow ratio of the first functional monomer, the second functional monomer, and the cross-linking agent is (1-10): (1-10): (1-5); The initiator di-tert-butyl peroxide is heated to 10-30° C., the first functional monomer 2-(dimethylamino)ethyl methacrylate is heated to 40-70° C., the second functional monomer methacrylic acid is heated to 40-60° C., and the crosslinking agent ethylene glycol diacrylate is heated to 45-60° C.; The expected thickness of the first film is 100-800 nm; the expected thickness of the second film is 100-200 nm; The antibacterial adhesion and bone-promoting polymer film is a double-layer polymer film, wherein the first film of the bottom layer is P(DMAEMA- co -MAA- co -EGDA), the second film on the upper layer is P(DMAEMA- co -MAA); The prepared antibacterial adhesion and osteogenic polymer film is an amphoteric polyelectrolyte film, in which positive and negative charges are combined with water molecules through ionic bonds, so that the polymer forms a hydration layer. The hydration layer serves as a physical protective layer to prevent bacteria from adhering to the surface of the film to form a biofilm, thereby achieving an antibacterial effect. The amphoteric polyelectrolyte film also has a high density of functional groups, which can promote the differentiation of preosteoblasts, making the antibacterial adhesion and osteogenic polymer film have an osteogenic effect.

2. The method for preparing an antibacterial osteogenic film by chemical vapor deposition technology according to claim 1, characterized in that: The chemical vapor deposition reactor controls the pressure to 0.1-1.0 Torr through a throttle valve, and controls the flow rate through a mass flow controller.

3. The method for preparing an antibacterial osteogenic film by chemical vapor deposition technology according to claim 1, characterized in that: The thickness of the first film and the second film are monitored by real-time laser interferometry.

4. The method for preparing an antibacterial osteogenic film by chemical vapor deposition technology according to claim 1, characterized in that: During the deposition process of forming the first thin film and the second thin film, the temperature of the substrate is controlled to be 30-60° C. by a water circulation system, and the temperature of the substrate is monitored by a thermocouple.

5. The method for preparing an antibacterial osteogenic film by chemical vapor deposition technology according to claim 1, characterized in that: The nickel-chromium wire is arranged 2.5-3 cm above the reaction table, and the predetermined heating temperature of the nickel-chromium wire is 200-400°C.

6. The method for preparing an antibacterial osteogenic film by chemical vapor deposition technology according to claim 1, characterized in that: The substrate is one of a plastic sheet, a titanium sheet, a basic calcium phosphate support or a silicon sheet.

7. Use of the antimicrobial adhesion bone-promoting polymer film obtained according to any one of the preparation methods described in claims 1-6 on the surface of bone regeneration materials.

Images