A membrane-coated drug-eluting stent, its preparation method and application in preventing post-orthopedic repair infection

Abstract

The present invention discloses a preparation method of a membrane-coated drug sustained-release stent. First, a gentamicin-sodium alginate-polyvinyl alcohol mixed solution is prepared. By using impregnation oscillation, gel modification and cross-linking, and freeze-drying techniques, a degradable drug-coated membrane for drug sustained release is constructed on the surface of a porous stent. After that, an effective drug sustained-release effect is achieved, and it has a bactericidal and antibacterial effect for a certain period of time. It has good practicability, non-toxicity, and biodegradability, and can be used for preventing infection after bone repair surgery.

Description

Technical Field

[0001] The present invention belongs to the field of drug sustained release and its composite special polymer materials, and particularly relates to a membrane-coated drug sustained release stent, a preparation method thereof, and an application in anti-infection after bone repair surgery. Background Art

[0002] With the improvement of the per capita income level in China, people's living and consumption patterns have begun to change. People's emotional needs have increased day by day. The transformation of pet-raising awareness and the conversion of pet roles have led to the rapid growth of China's pet market. With the continuous development of China's pet market, the future pet economy has a broader prospect.

[0003] For some relatively active pets, such as pet dogs and pet cats, the risk of bone injury has increased significantly. In addition, some orthopedic diseases of pets themselves, such as developmental deformities, congenital bone structure abnormalities, osteomas, etc., have to undergo bone correction, bone repair and other surgeries. However, the bone sizes or the affected areas of different parts of different pets are different, and they cannot be carried out with a unified specification. And postoperative infection in orthopedics is also a problem that cannot be ignored. The bone repair 3D printing technology can customize the shapes and specifications of implants and substitutes, and prevent postoperative infection, and is becoming more and more popular in the field of orthopedic medicine.

[0004] At present, the bone repair materials mainly include natural bone repair materials, artificial bone repair materials, metals, and non-metallic materials. The natural bone repair material is autologous bone, and its advantage is that it is taken from the autologous body and has good biocompatibility, but the bone mass is limited, and it will cause additional blood loss and trauma to the autologous body; most of the artificial bone repair materials are xenogeneic bones, which come from donated tissues and have good osteoinductivity and osteoconductivity, but the sources are few and the price is high; the metals mainly include porous titanium and titanium alloys, stainless steel, etc., which have wide sources, low prices, and high strength. The disadvantage is that they cannot form bone integration and have poor plasticity; the non-metallic materials have wide sources, including various bioceramics, polymer materials, composite materials, etc., with good biocompatibility and low prices, but most of the materials are not suitable for new bone growth. Therefore, there is a great need for a bone repair stent with good biocompatibility, cell adhesion, mechanical properties close to natural bone and capable of preventing postoperative infection to meet the needs of medical development.

[0005] Chinese Patent (Patent No.: CN202210938130.4) discloses a preparation method of a bone repair scaffold. The preparation process is as follows: putting a polyetheretherketone sheet into concentrated sulfuric acid to prepare sulfonated polyetheretherketone; preparing a hydrogel solution by mixing polyvinyl alcohol, aspirin, gelatin and nano-hydroxyapatite in a preset ratio; pouring the sulfonated polyetheretherketone sheet and the hydrogel solution into a mold together, subjecting them to multiple cycles of freeze-thawing and then soaking them in an anhydrous calcium chloride solution, and drying to obtain a polyetheretherketone-loaded drug hydrogel bilayer bone repair scaffold; adding aspirin to achieve the purpose of anti-thrombosis and analgesia after bone repair surgery, which is completely different from the purpose of drug sustained release for preventing postoperative infection in the technical solution of this application, and the application focuses are also quite different.

[0006] Chinese Patent (Patent No.: CN202110823078.3) discloses a preparation method of a 3D printed scaffold with long-acting antibacterial and self-lubricating functions. The mass fractions of the raw materials are as follows: 87-95 parts of PEEK powder, 2-5 parts of zinc oxide, 1-3 parts of nano-silver, and 2-5 parts of zeolitic imidazolate framework material. After high-temperature twin-screw mixing at 350-370°C for 10-30 minutes, it is prepared into a wire, and then printed into a scaffold. Through surface treatment, a PEEK-NH2 scaffold is obtained, and then grafted with hyaluronic acid or sodium alginate molecules to obtain a PEEK-CHO scaffold, and then immersed in a protein solution for reaction to obtain a 3D printed PEEK scaffold with long-acting antibacterial and self-lubricating functions. Compared with this article, although the purpose is the same, which is antibacterial, the modification of the scaffold in this article is different from it. The scaffold is soaked in a sodium alginate-polyvinyl alcohol solution. Relative to the process of obtaining -NO2 groups by treating its surface with concentrated sulfuric acid and concentrated nitric acid, then obtaining -NH2 groups by treating with SnCl2, then grafting with hyaluronic acid or sodium alginate molecules and then oxidizing the hyaluronic acid or sodium alginate molecules to obtain -CHO groups, and finally soaking in a protein solution containing antibiotics for reaction to obtain a 3D printed PEEK scaffold with long-acting antibacterial and self-lubricating functions, the method of obtaining the gel-modified scaffold in the application technical solution is simpler, more convenient, non-toxic, harmless and gentler.

[0007] Chinese Patent (Patent No.: CN202011573500.6) discloses a preparation method of a polyetheretherketone wollastonite whisker composite bone repair scaffold. This preparation method synthesizes a polyetheretherketone matrix material by the original polymerization method using hydroquinone and 4,4'-difluorobenzophenone under the catalysis of basic oxides. When the polyetheretherketone is in a slurry state, wollastonite whiskers are added to improve the mechanical properties of polyetheretherketone by whisker reinforcement. At the same time, silicon ions and calcium ions are introduced into the polyetheretherketone matrix to improve the bioactivity of the polyetheretherketone material. It uses self-synthesized polyetheretherketone composite wollastonite whiskers to improve the mechanical properties and bioactivity of the material, which is different from the polyetheretherketone scaffold mainly used for bone repair and postoperative anti-infection introduced in this article, targeting different goals. It uses wollastonite whiskers to improve the mechanical properties of the material and introduces silicon ions and calcium ions to improve bioactivity, which is completely different from the technical solution of this application that uses short carbon fiber as the reinforcing material and sodium alginate to regulate cell metabolism mechanism and modification method.

[0008] Chinese Patent (Patent No.: CN202211511327.6) discloses a surface large through-hole structure radial gradient hydroxyapatite / polyetheretherketone composite material scaffold and its preparation method and application. The preparation process is that calcium hydrogen phosphate dihydrate, calcium hydroxide and polyetheretherketone are respectively ball-milled and pre-reacted according to different ratios, and different proportions of sodium chloride particles are added to the surface filler to obtain a mixture; after pre-pressing and forming through different diameter molds respectively and nesting them into a gradient composition green body; heating by spark plasma sintering under high pressure to obtain a dense rod; dissolving the sodium chloride particles in water to obtain a surface large through-hole structure radial gradient hydroxyapatite / polyetheretherketone composite material scaffold. First of all, the composite materials added in it are very different from the composite materials of the technical solution of this application. Secondly, its scaffold processing method is also different. It is obtained by molding and sintering, which is significantly different from the technical solution of this application that makes wire and then prints. Moreover, this method solves the problems such as difficult hot pressing forming of radial gradient materials, uneven forming temperature of gradient materials and reduction of mechanical properties due to pore structure, which is very different from the purpose of this application aimed at anti-infection bone repair. Summary of the Invention

[0009] In view of the above problems, the present invention provides a preparation method of a membrane-coated drug sustained-release scaffold.

[0010] In order to achieve the above object, the technical solution provided by the present invention is:

[0011] A preparation method of a membrane-coated drug sustained-release scaffold, comprising the following steps:

[0012] (1) Prepare a polyvinyl alcohol solution and a sodium alginate solution; add the obtained sodium alginate solution to the polyvinyl alcohol solution and disperse evenly to obtain a sodium alginate-polyvinyl alcohol mixed solution;

[0013] Among them, the mass concentrations of sodium alginate and polyvinyl alcohol in the sodium alginate-polyvinyl alcohol mixed solution are 1-4% and 3-6% respectively;

[0014] (2) Add a certain amount of gentamicin to the obtained sodium alginate-polyvinyl alcohol mixed solution, keep the temperature at 35-40 °C, disperse evenly to obtain a gentamicin-sodium alginate-polyvinyl alcohol mixed solution;

[0015] Among them, the dosage of gentamicin is such that its concentration reaches 0.1-0.3 wt%;

[0016] (3) Mix a certain proportion of carbon fiber and polyether ether ketone evenly, dry the mixed material and then carry out melt extrusion to obtain a 3D printing composite wire;

[0017] The mass ratio between the carbon fiber and polyether ether ketone used is 1:4-6;

[0018] Among them, the melt extrusion is carried out by a twin-screw extruder, and the temperature is set as follows: the first stage is 340-350 °C, the second stage is 350-360 °C, the third stage is 360-365 °C, and the screw extrusion speed is 35 rpm;

[0019] (4) According to the designed structural model, print the obtained 3D printing composite wire by a 3D printing device, then soak it in ethanol, carry out ultrasonic treatment at 35-40 °C, and then dry it to obtain a porous bone repair scaffold;

[0020] (5) Immerse the obtained porous bone repair scaffold in the gentamicin-sodium alginate-polyvinyl alcohol mixed solution, and carry out constant temperature oscillation at 35-40 °C for 20-30 h; take it out and then soak it in a (3 wt%) calcium chloride aqueous solution at room temperature for 15-25 min, (freeze) dry it to obtain a membrane-coated drug sustained-release scaffold.

[0021] The polyvinyl alcohol has a molecular weight of 30,000-80,000; the sodium alginate has a molecular weight of 20,000-50,000; the carbon fiber has a length of 150-200 μm and a wire diameter of 5-7 μm.

[0022] The membrane-coated drug sustained-release scaffold of the present invention can be applied to prevent infection after bone repair surgery.

[0023] The technical solution of the present invention has the following positive and beneficial effects:

[0024] (1) The present invention uses polyvinyl alcohol as the matrix material for preparing the degradable film. It is a safe polymer, almost non-toxic and harmless to the human body, with extremely few side effects or even no side effects, and has good biocompatibility. Especially in the medical field, aqueous gels are widely used in ophthalmology, wound dressings, and artificial joints, and are also used in artificial kidney membranes, etc. It is a commonly used safe film-forming agent, with strong practicality and application advantages.

[0025] (2) The present invention uses sodium alginate as the cross-linking agent. It is a natural polysaccharide and an ideal natural biomedical material. Due to its good biocompatibility and degradability, it is widely used in the fields of chemistry, textiles, medicine, biology, etc. The materials used in the present invention complement and promote each other. Sodium alginate contains functionalized carboxyl groups, and polyvinyl alcohol has polyhydroxy properties. It can be more determined through infrared spectrograms that the two form a stable interpenetrating gel network structure through hydrogen bonding, promoting the gelation of polyvinyl alcohol. Through cytotoxicity tests, it is confirmed that there are almost no obvious changes in the toxicological properties of the two materials during the gelation process. Compared with other organic cross-linking agents, the reaction conditions are milder, the toxicity is negligible, and the influence is even less. The problem of residue and volatilization of organic solvents does not need to be considered, and the safety is better and the reliability is higher.

[0026] (3) The present invention uses gentamicin as the drug for slow release. It is an aminoglycoside antibiotic, mainly used for treating bacterial infections, especially infections caused by Gram-negative bacteria, and has a significant effect in anti-infection. At the same time, it can be used in combination with penicillin drugs, penicillins against Pseudomonas, and vancomycin. Compared with other antibiotics, such as cephalosporin antibiotics, etc., its application space is wider and the restricted conditions are fewer.

[0027] (4) The present invention uses freeze-drying, which can avoid the influence of heat drying on the gel structure and the performance of the drug, and has higher stability. At the same time, freeze-drying can form a porous structure on the surface of the gel, which is more conducive to cell adhesion and provides a larger attachment space for cell growth.

[0028] (5) The present invention uses a gel to prepare a porous bone repair scaffold for drug slow release by coating a degradable film. The preparation process is mild and safe, the raw materials used are green, environmentally friendly and pollution-free, the technical cost is low, the preparation process is relatively simple and convenient, and the preparation advantages are obvious. Moreover, the porous scaffold provides more spatial positions and drug loading capacities for the adhesion of the gel on the surface, has good practicality, and has significant application significance in anti-infection after bone repair surgery. Description of the Drawings

[0029] To more clearly illustrate the technical solution of the present invention, the accompanying drawings required for use in the embodiments will be briefly introduced below. Obviously, the accompanying drawings in the following description are only partial embodiments of the present invention.

[0030] Figure 1 This is the process flow chart for the preparation of the present invention.

[0031] Figure 2 This is the stent photo diagram of Examples 1, 2, 3, 4, 5 and Comparative Example 1 of the present invention.

[0032] Figure 3 This is the antibacterial experiment of Escherichia coli and Staphylococcus aureus in Examples 1, 2, 3, 4, 5 and Comparative Example 1 of the present invention. Embodiment

[0033] All features disclosed in this specification, or all steps in the disclosed methods or processes, except for those that are mutually exclusive, can be combined in any manner.

[0034] Any feature disclosed in this specification (including any additional claims, abstract, and drawings), unless specifically stated, can be replaced by other equivalent or similar-purpose alternative features. That is, unless specifically stated, each feature is only an example of a series of equivalent or similar features. Among them, the materials used in the following examples are as follows, but the present invention is not limited thereto:

[0035] The sodium alginate-gentamicin-polyvinyl alcohol mixed solution is prepared by the following steps:

[0036] (1) Preparation of polyvinyl alcohol solution: Add polyvinyl alcohol to deionized water, heat to 96°C and stir for 3 h. After complete dissolution, continue to stir and cool to 37°C; the concentration of polyvinyl alcohol is 9%.

[0037] (2) Preparation of sodium alginate-polyvinyl alcohol mixed solution: Add sodium alginate to deionized water, heat to 60°C and stir for 2 h. After complete dissolution, a sodium alginate solution with a concentration of 3.6% is obtained. After continuing to stir and cooling to 37°C, it is slowly added to the sodium alginate-polyvinyl alcohol mixed solution obtained in step (1), and stirring and dispersion are continued at 37°C for 2 h; the mass ratio of the sodium alginate solution to the polyvinyl alcohol solution is 1:1.

[0038] (3) Preparation of gentamicin-sodium alginate-polyvinyl alcohol mixed solution: Add gentamicin to the sodium alginate-polyvinyl alcohol mixed solution obtained in step (2) to make the gentamicin concentration reach 0.2%, keep at 37°C, and stir for 30 min; finally, the mixed solution is subjected to ultrasonic dispersion treatment at 37°C for 30 min.

[0039] Preparation of 3D printing composite wire: The composite material, by weight, includes 5 parts of polyether ether ketone and 1 part of short carbon fiber. First, use a V-type mixer to fully disperse and mix the carbon fiber and polyether ether ketone evenly. Then, place the evenly mixed material in a vacuum drying oven at 120°C for vacuum drying for 12 hours. Take it out, and use a micro twin-screw extruder to heat, melt, extrude, cool, and collect the mixed material to obtain 3D printing composite wire. Among them, the temperature of the twin-screw is set as follows: the first section is 340°C, the second section is 350°C, and the third section is 360°C, and the screw extrusion speed is 35 rpm.

[0040] Preparation of porous bone repair scaffold: Use the 3D printing composite wire prepared above with a 3D printing device to print the required porous bone repair scaffold according to the designed structural model. Immerse the obtained porous bone repair scaffold in an appropriate amount of absolute ethanol, set the temperature to 37°C, and ultrasonically treat it in an ultrasonic treatment device for 5 minutes. Take it out and place it in a vacuum drying oven at 120°C for drying for 3 hours to obtain a porous bone repair scaffold.

[0041] Preparation of membrane-coated drug sustained-release scaffold: Place the porous scaffold in a 10 ml centrifuge tube, add the prepared mixed solution to the centrifuge tube, and place the centrifuge tube in a constant temperature oscillator to maintain constant temperature oscillation at 37°C for 24 hours. Take out the porous scaffold, immerse the porous scaffold in a 3% calcium chloride aqueous solution at 37°C for 20 minutes for cross-linking reaction. After completion, take it out and place it in a freeze dryer for freeze drying for 48 hours to obtain a membrane-coated drug sustained-release scaffold.

[0042] Example 1: Add polyvinyl alcohol particles to deionized water, heat up to 96°C and stir for 3 hours. After fully dissolving, continue to stir and cool to 37°C. Add sodium alginate to deionized water, heat up to 60°C and stir for 2 hours. After fully dissolving, continue to stir and cool to 37°C, and then slowly add the cooled sodium alginate solution to the polyvinyl alcohol solution, and continue to stir and disperse at 37°C for 2 hours. Add gentamicin to the obtained sodium alginate-polyvinyl alcohol composite solution to prepare a composite medicament solution with a concentration of 2 mg / ml, keep it at 37°C, and stir for 30 minutes. Finally, place the mixed solution in an ultrasonic dispersion treatment at 37°C for 30 minutes. Use a 3D printing device to print a porous bone repair scaffold according to the structural model design. Place the porous scaffold in a 10 ml centrifuge tube. First, add the prepared mixed solution to the centrifuge tube, and then place the centrifuge tube in a constant temperature oscillator to maintain constant temperature oscillation at 37°C for 24 hours. Take out the porous scaffold, immerse the porous scaffold in a 3% calcium chloride aqueous solution at 37°C for 20 minutes for cross-linking reaction. After completion, take it out and place it in a freeze dryer for freeze drying for 48 hours to obtain a membrane-coated drug sustained-release scaffold.

[0043] Example 2: Add polyvinyl alcohol particles to deionized water, heat up to 96 °C and stir for 3 h. After complete dissolution, continue to stir and cool to 37 °C. Add gentamicin to the obtained polyvinyl alcohol solution to prepare a composite medicament solution with a concentration of 2 mg / ml, maintain at 37 °C, and stir for 30 min. Finally, subject the mixed solution to ultrasonic dispersion treatment at 37 °C for 30 min. Use a 3D printing device to print a porous bone repair scaffold according to the structural model. Place the porous scaffold in a 10-ml centrifuge tube, then add the prepared mixed solution to the centrifuge tube. Then, place the centrifuge tube in a thermostatic shaker and maintain constant temperature oscillation at 37 °C for 24 h. Take out the porous scaffold, soak the porous scaffold in a 3% calcium chloride aqueous solution at 37 °C for 20 min for crosslinking reaction. After completion, take out and place it in a freeze dryer for freeze drying for 48 h to obtain a membrane-coated drug sustained-release scaffold.

[0044] Example 3: Add polyvinyl alcohol particles to deionized water, heat up to 96 °C and stir for 3 h. After complete dissolution, continue to stir and cool to 37 °C. Add sodium alginate to deionized water, heat up to 60 °C and stir for 2 h. After complete dissolution, continue to stir and cool to 37 °C, then slowly add the cooled sodium alginate solution to the polyvinyl alcohol solution, maintain at 37 °C and continue to stir and disperse for 2 h. Finally, subject the mixed solution to ultrasonic dispersion treatment at 37 °C for 30 min. Use a 3D printing device to print a porous bone repair scaffold according to the structural model. Place the porous scaffold in a 10-ml centrifuge tube, then add the prepared mixed solution to the centrifuge tube. Then, place the centrifuge tube in a thermostatic shaker and maintain constant temperature oscillation at 37 °C for 24 h. Take out the porous scaffold, soak the porous scaffold in a 3% calcium chloride aqueous solution at 37 °C for 20 min for crosslinking reaction. After completion, take out and place it in a freeze dryer for freeze drying for 48 h to obtain a membrane-coated drug sustained-release scaffold.

[0045] Example 4: Add polyvinyl alcohol particles to deionized water, heat up to 96 °C and stir for 3 h. After complete dissolution, continue to stir and cool to 37 °C. Subject the polyvinyl alcohol solution to ultrasonic dispersion treatment at 37 °C for 30 min. Use a 3D printing device to print a porous bone repair scaffold according to the structural model. Place the porous scaffold in a 10-ml centrifuge tube, then add the prepared polyvinyl alcohol solution to the centrifuge tube. Then, place the centrifuge tube in a thermostatic shaker and maintain constant temperature oscillation at 37 °C for 24 h. Take out the porous scaffold, soak the porous scaffold in a 3% calcium chloride aqueous solution at 37 °C for 20 min for crosslinking reaction. After completion, take out and place it in a freeze dryer for freeze drying for 48 h to obtain a membrane-coated drug sustained-release scaffold.

[0046] Example 5: Sodium alginate was added to deionized water, and the temperature was raised to 60 °C and stirred for 2 h. After complete dissolution, stirring was continued while cooling to 37 °C. The sodium alginate solution was subjected to ultrasonic dispersion treatment at 37 °C for 30 min. A porous bone repair scaffold was printed using a 3D printing device according to the structural model design. The porous scaffold was placed in a 10 ml centrifuge tube. First, the prepared sodium alginate solution was added to the centrifuge tube, and then the centrifuge tube was placed in a thermostatic oscillator and kept at a constant temperature of 37 °C and oscillated for 24 h. The porous scaffold was taken out and immersed in a 3% calcium chloride aqueous solution at 37 °C for 20 min for crosslinking reaction. After completion, it was taken out and placed in a freeze dryer for freeze drying for 48 h to obtain a membrane-coated drug sustained-release scaffold.

[0047] Comparative Example 1: Polyvinyl alcohol particles were added to deionized water, and the temperature was raised to 96 °C and stirred for 3 h. After complete dissolution, stirring was continued while cooling to 37 °C. The polyvinyl alcohol solution was subjected to ultrasonic dispersion treatment at 37 °C for 30 min. A porous bone repair scaffold was printed using a 3D printing device according to the structural model design. The porous scaffold was placed in a 10 ml centrifuge tube, and then the prepared polyvinyl alcohol solution was added to the centrifuge tube. Then, the centrifuge tube was placed in a thermostatic oscillator and kept at a constant temperature of 37 °C and oscillated for 24 h. The porous scaffold was taken out and immersed in a 3% calcium chloride aqueous solution at 37 °C for 20 min for crosslinking reaction. After completion, it was taken out and placed in a freeze dryer for freeze drying for 48 h to obtain a porous bone repair scaffold.

[0048] Performance evaluation: The evaluation results of the scaffold samples obtained in the examples and comparative examples are shown in Tables 1 and 2.

[0049] Table 1 Test results of porous scaffold samples in examples and comparative examples

[0050]

[0051] Table 2 Drug sustained-release concentration results of Example 1 and Example 2

[0052]

[0053] Test results: It can be seen from the test results of the embodiments that the materials of Embodiments 1, 2, 3, 4, 5 and Comparative Example 1 have no significant toxicity to cells; Embodiment 1 has a significant inhibitory effect on Escherichia coli and Staphylococcus aureus; although the material of Embodiment 2 also shows no cytotoxicity and has a significant inhibitory effect on Escherichia coli and Staphylococcus aureus, the drug sustained-release effect is not significant; Embodiments 3, 4, 5 and Comparative Example 1 have no antibacterial effect on Escherichia coli and Staphylococcus aureus; the drug sustained-release rate of Embodiment 1 is most obvious in the first 3 days and then gradually weakens, but still shows a sustained-release trend; although Embodiment 2 also shows the same sustained-release trend as Embodiment 1, the cumulative drug concentration of Embodiment 2 on the 15th day is lower than the cumulative drug concentration of Embodiment 1 on the 1st day, while Embodiments 3, 4, 5 and Comparative Example 1 have no drug sustained-release effect.

[0054] In the accompanying drawings Figure 1 is the preparation flow chart of the present invention, Figure 2 is the scaffold photo of Embodiments 1, 2, 3, 4, 5 and Comparative Example 1 of the present invention. It can be seen from the figure that there are significant differences in the appearance of the bone repair scaffolds obtained by Embodiment 1 and Embodiment 3 and those obtained by Embodiments 2, 4, 5 and Comparative Example 1. There is no significant difference in the appearance of the bone repair scaffolds obtained by Embodiment 1 and Embodiment 3. At the same time, there is also no significant difference in the appearance of the bone repair scaffolds obtained by Embodiments 2, 4, 5 and Comparative Example 1. Among them, there is an obvious gel film attached to the surface of the bone repair scaffolds obtained by Embodiment 1 and Embodiment 3, while no gel film can be seen attached to the surface of the scaffolds in Embodiments 2, 4, 5 and Comparative Example 1, and no obvious changes in the scaffolds can be observed either. Figure 3 is the antibacterial experiment results of Escherichia coli and Staphylococcus aureus of the embodiments and Comparative Example 1 of the present invention. It can be seen that the antibacterial effects of the scaffolds of Embodiment 1 and Comparative Example 1 on Escherichia coli and Staphylococcus aureus are very significant, and the antibacterial effect on Staphylococcus aureus is significantly stronger than that on Escherichia coli. Since no drug components are added in Comparative Example 1, there is no antibacterial effect. The antibacterial intensity of Embodiment 1 is stronger than that of Comparative Example 1, which also shows that the surface of the gel-modified porous bone repair scaffold can load more drug amounts and has a more significant antibacterial effect.

Claims

1. A preparation method of a membrane-coated drug-eluting stent, characterized in that: It includes the following steps: (1) Prepare a polyvinyl alcohol solution and a sodium alginate solution; Add the obtained sodium alginate solution to the polyvinyl alcohol solution, disperse evenly to obtain a sodium alginate-polyvinyl alcohol mixed solution; (2) Add a certain amount of gentamicin to the obtained sodium alginate-polyvinyl alcohol mixed solution, keep the temperature at 35 - 40 °C, disperse evenly to obtain a gentamicin-sodium alginate-polyvinyl alcohol mixed solution; (3) Mix a certain proportion of carbon fiber and polyether ether ketone evenly, and after drying, melt and extrude the mixed material to obtain a 3D printing composite wire; (4) According to the designed structural model, print and form the obtained 3D printing composite wire with a 3D printing device, then soak it in ethanol, perform ultrasonic treatment at 35 - 40 °C, and then dry to obtain a porous bone repair scaffold; (5) Immerse the obtained porous bone repair scaffold in the gentamicin-sodium alginate-polyvinyl alcohol mixed solution, and perform constant temperature oscillation at 35 - 40 °C for 20 - 30 h; take it out and soak it in an aqueous calcium chloride solution at room temperature for 15 - 25 min, and dry to obtain a membrane-coated drug sustained-release scaffold.

2. The preparation method according to claim 1, characterized in that: The mass concentrations of sodium alginate and polyvinyl alcohol in the sodium alginate-polyvinyl alcohol mixed solution are 1 - 4% and 3 - 6% respectively.

3. The preparation method according to claim 1, characterized in that: The dosage of the gentamicin is such that its concentration reaches 0.1 - 0.3 wt%.

4. The preparation method according to claim 1, characterized in that: The mass ratio between the carbon fiber and the polyether ether ketone is 1:4 - 6.

5. The preparation method according to claim 1, characterized in that: The melt extrusion is carried out by a twin-screw extruder, and the temperature is set as follows: the first section is 340 - 350 °C, the second section is 350 - 360 °C, the third section is 360 - 365 °C, and the screw extrusion speed is 35 rpm.

6. The preparation method according to claim 1, characterized in that: The concentration of the aqueous calcium chloride solution is 3 wt%.

7. The preparation method according to claim 1, characterized in that: The molecular weight of the polyvinyl alcohol is 30000 - 80000; the molecular weight of the sodium alginate is 20000 - 50000; the length of the carbon fiber is 150 - 200 μm, and the wire diameter is 5 - 7 μm.

8. The preparation method according to claim 1, characterized in that: The drying in step (5) is freeze-drying.

9. A membrane-coated drug sustained-release scaffold obtained by the preparation method according to any one of claims 1 - 8.

10. Use of the membrane-coated drug sustained-release scaffold according to claim 9 in the preparation of a material for preventing infection after bone repair.

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