A drug-loaded porous magnesium alloy bone scaffold and its preparation method

Abstract

This invention belongs to the field of medical materials technology, specifically referring to a drug-loaded porous magnesium alloy bone scaffold and its preparation method. The drug-loaded porous magnesium alloy bone scaffold is composed of the following raw materials in parts by weight: 55 parts magnesium alloy, 6-10 parts corrosion inhibitor, 1 part drug-loaded gel, 2-4 parts antibacterial bone-promoting agent, and 3 parts gelatin. This invention achieves sustained drug release by fabricating magnesium alloy into microtubes and filling the interior with a drug-loaded hydrogel; gelatin is sprayed onto the surface and adhered through Mg-N coordination bonds, bonded to the corrosion inhibitor, and hot-pressed. The components form an interpenetrating network with the gelatin to enhance bonding and react with the magnesium alloy to form a protective film; simultaneously, Ca... 2+ The process initiates cross-linking of sodium alginate, forming a stable anti-corrosion barrier. Finally, an antibacterial and bone-promoting mixture containing modified chitosan and thermosensitive polymer is sprayed on. Through complexation reaction and temperature control, the bone-promoting components are evenly dispersed around the implant, improving tissue compatibility.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically referring to a drug-loaded porous magnesium alloy bone scaffold and its preparation method. Background Technology

[0002] In the field of orthopedic medicine, magnesium alloys have become an ideal bone implant material due to their good biocompatibility, biodegradability, and mechanical properties similar to human bone tissue.

[0003] The rapid corrosion rate of magnesium alloys in vivo, their limited drug release capacity, and the interfacial bonding issues with surrounding bone tissue severely restrict their clinical application. Existing magnesium alloy bone scaffolds struggle to achieve precise and long-term drug release and lack effective means to construct a stable corrosion-resistant barrier and a microenvironment that promotes bone tissue growth. Furthermore, enhancing the biocompatibility of implanted materials with surrounding tissues and avoiding immune rejection are also critical issues that urgently need to be addressed.

[0004] Based on the above, the development of magnesium alloy bone scaffold materials that combine drug delivery, corrosion resistance, and bone repair promotion functions is of great significance for improving the therapeutic effect and safety of orthopedic implants. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention discloses a drug-loaded porous magnesium alloy bone scaffold, achieving multiple performance optimizations through the following process: First, magnesium alloy is fabricated into microtubes, which are then filled with a drug-loaded hydrogel for slow drug release. Simultaneously, a gelatin solution is sprayed onto the surface of the magnesium alloy precursor, utilizing the Mg-N coordination bonds formed between nitrogen atoms in the amino groups of the gelatin molecules and magnesium ions to ensure strong adhesion. Next, an anti-corrosion agent is bonded to the surface of the magnesium alloy precursor and hot-pressed. The ester and hydroxyl functional groups in the anti-corrosion agent form an interpenetrating network structure with the gelatin layer molecules through segment diffusion entanglement, enhancing interfacial bonding. Its active ingredients chemically react with the magnesium alloy surface to form a dense protective film, and the calcium chloride released under atomization conditions... 2+ A cross-linking reaction occurs with sodium alginate in the corrosion inhibitor, promoting the cross-linking of sodium alginate molecules into a three-dimensional network structure through Ca-O coordination bonds. This enhances the stability of the corrosion inhibitor and forms an anti-corrosion barrier on the magnesium alloy surface. Finally, the antibacterial bone-promoting mixture is sprayed onto the surface of the corrosion-resistant magnesium alloy implant. The phosphate groups in the modified chitosan undergo a complexation reaction with the metal ions on the surface of the corrosion inhibitor. Combined with the temperature sensitivity of poly-N-isopropylacrylamide, external temperature control promotes the uniform dispersion of the bone-promoting components around the implant, improving the compatibility of the implant material with the surrounding tissues.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is a drug-loaded porous magnesium alloy bone scaffold, comprising, from the inside out, magnesium alloy, gelatin, corrosion inhibitor, and antibacterial bone-promoting agent. The magnesium alloy is filled with a drug-loaded gel. The mass proportions of the above materials are as follows: 55 parts magnesium alloy, 6-10 parts corrosion inhibitor, 1 part drug-loaded gel, 2-4 parts antibacterial bone-promoting agent, and 3 parts gelatin.

[0007] Furthermore, the method for preparing the drug-loaded gel includes the following steps:

[0008] A. Weigh 3-4 parts of polylactic acid, 2.5-3.5 parts of polycaprolactone and 1-2 parts of polyethylene glycol, mix them and heat them together in an oil bath at 120-150℃ for 1 hour to obtain a copolymer. Then, rapidly cool it at -30℃ for 24 hours, pulverize it, and sieve it using a 100-mesh sieve to obtain fine copolymer particles.

[0009] B. Add the copolymer particles obtained in step A and 1 part of antibiotic to 10 parts of deionized water, stir for 30 min at a speed of 300 r / min, then add 2-3 parts of gel, lower the temperature to -10℃ and cure for 24 h, pulverize, and sieve using a 100 mesh screen to obtain the drug-loaded gel.

[0010] Furthermore, the method for preparing the corrosion-resistant material includes the following steps:

[0011] 1. Weigh 4-7 parts of silk fibroin and 6-10 parts of polycaprolactone, add them to 40 parts of deionized water, sonicate for 30 minutes at a power of 0.5 kW, stir for 30 minutes at a speed of 300 r / min, and centrifuge for 15 minutes at a speed of 5000 r / min to obtain a mixed solution. Electrospin the obtained mixed solution under a working voltage of 15 kV and a receiving distance of 10 cm to obtain a fiber membrane.

[0012] 2. Weigh 5 parts of sodium alginate and add them to 15 parts of deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution A. Dip and deposit solution A onto the fiber membrane obtained in step 1 to obtain a composite membrane.

[0013] 3. Weigh 2-4 parts of calcium chloride and 6-8 parts of hydroxyapatite and add them to 25 parts of deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution B. Atomize solution B and spray it onto the composite film obtained in step 2 to obtain the corrosion inhibitor precursor.

[0014] 4. The corrosion-resistant precursor obtained in step 3 is photothermally cured for 20 minutes under ultraviolet light at a wavelength of 280nm, at a distance of 15cm, to obtain the corrosion-resistant material.

[0015] Furthermore, the preparation method of the antibacterial bone-promoting substance includes the following steps:

[0016] (a) Weigh 3-6 parts of modified chitosan and add it to 30 parts of deionized water. Heat at 70°C for 2 hours and stir at 300 r / min for 30 minutes to obtain reaction solution I.

[0017] (b) Weigh 2.5-4.5 parts of poly-N-isopropylacrylamide and add it to the reaction solution I obtained in step (a). Stir at 300 r / min for 30 min. Then add 2 parts of hyaluronic acid and stir at 500 r / min for 30 min to obtain the complex. Freeze-dry the complex at -20℃ for 72 h to obtain the antibacterial bone-promoting substance.

[0018] Furthermore, the preparation method of the modified chitosan includes the following steps:

[0019] (α) Weigh 5-8 parts of chitosan and add it to 30 parts of deionized water. Stir for 30 minutes at a speed of 500 r / min to obtain a solution.

[0020] (β) Weigh 3-5 parts of potassium dihydrogen phosphate and 0.8 parts of arginine and add them to the solution obtained in step (α). Stir for 30 minutes at a speed of 300 r / min to obtain the reaction solution.

[0021] (γ) The reaction solution obtained in step (β) was subjected to hydrothermal reaction at a temperature of 90-120℃ for 6 hours, naturally cooled to room temperature, centrifuged at 8000 r / min for 20 min, washed 5 times with deionized water, and then placed in a vacuum drying oven at a temperature of 65℃ for 24 hours to obtain modified chitosan.

[0022] This invention also provides a method for preparing a drug-loaded porous magnesium alloy bone scaffold, comprising the following steps:

[0023] Step 1. Weigh 55 parts of magnesium alloy and draw them at 0.3 m / min at 300℃ to obtain a 3 mm thick magnesium alloy tube. Then, drill holes in the magnesium alloy tube to a hole density of 280 holes / cm³. 2 Then, a 10μm magnesium oxide ceramic layer was grown in situ through micro-arc oxidation treatment, with a voltage of 450V, a frequency of 150Hz, and an oxidation time of 10min, resulting in a microporous filled tube with a pore size of 200μm.

[0024] Step 2. Weigh 1 part of the drug-loaded gel and fill it into the microporous filling tube obtained in Step 1, wherein the filling pressure is 0.5 MPa, and the filling tube is obtained.

[0025] Step 3. The filled tube obtained in Step 2 is subjected to laser texturing treatment with a wavelength of 1065nm and a texturing depth of 50μm to obtain a texturing composite magnesium alloy tube. 3 parts of gelatin are weighed and added to 3 parts of deionized water. The mixture is stirred for 10min at a speed of 500r / min to obtain a gelatin solution. The gelatin solution is deposited onto the surface of the texturing composite magnesium alloy tube to obtain an activated magnesium alloy tube.

[0026] Step 4. Weigh 6-10 parts of the corrosion-resistant material and evenly apply it to the surface of the activated magnesium alloy pipe. Hot press it for 20 minutes at a temperature of 180-240℃ and a pressure of 15MPa to obtain the corrosion-resistant magnesium alloy implant.

[0027] Step 5. Weigh 2-4 parts of antibacterial bone-promoting agent and add 5 parts of deionized water. Stir at 500 r / min for 30 min to obtain a mixture. Spray the mixture onto the surface of the corrosion-resistant magnesium alloy implant obtained in Step 4 with a spray thickness of 30 μm. Sterilize at 110℃ and 0.1 MPa for 30 min, and then allow it to cool naturally to room temperature to obtain a drug-loaded porous magnesium alloy bone scaffold.

[0028] The beneficial effects achieved by this invention are as follows:

[0029] The drug-loaded porous magnesium alloy bone scaffold prepared by the present invention is made into a microtube of magnesium alloy, and a drug-loaded hydrogel is filled and fixed inside it to achieve slow release of the drug. A gelatin solution is sprayed onto the surface of the magnesium alloy precursor. The nitrogen atom in the amino group of the gelatin molecule can form a Mg-N coordination bond with magnesium ions, thereby making the gelatin firmly attached to the surface of the magnesium alloy.

[0030] The drug-loaded porous magnesium alloy bone scaffold prepared by this invention, when an anti-corrosion agent is attached to the surface of the magnesium alloy precursor and subjected to hot pressing, exhibits the following effects: Firstly, the ester and hydroxyl functional groups in the anti-corrosion agent, under the influence of heat and pressure, undergo chain segment diffusion and entanglement with molecules in the gelatin layer, forming an interpenetrating network structure and enhancing interfacial bonding. Secondly, the active ingredients in the anti-corrosion agent chemically react with the magnesium alloy surface to form a dense protective film. During this process, calcium chloride, under atomization, releases Ca... 2+ It undergoes a cross-linking reaction with sodium alginate in the corrosion inhibitor; the carboxyl groups on the sodium alginate molecular chain react with Ca... 2+ The formation of Ca-O coordination bonds promotes the cross-linking of sodium alginate molecules, forming a three-dimensional network structure. This cross-linked structure not only enhances the stability of the corrosion inhibitor itself, but also forms a dense anti-corrosion barrier on the surface of the magnesium alloy, effectively blocking the contact between external corrosive media and the magnesium alloy, further improving the corrosion resistance of the magnesium alloy.

[0031] The drug-loaded porous magnesium alloy bone scaffold prepared in this invention involves spraying an antibacterial bone-promoting mixture onto the surface of a corrosion-resistant magnesium alloy implant. The phosphate groups in the modified chitosan then complex with the metal ions on the surface of the corrosion-resistant material. The presence of poly(N-isopropylacrylamide), due to its thermosensitive nature, effectively promotes the uniform dispersion of the bone-promoting components in the surrounding environment of the implant through external temperature control, thereby enhancing the biocompatibility between the implant material and surrounding tissues. Attached Figure Description

[0032] Figure 1 This is a diagram illustrating the preparation method of the drug-loaded porous magnesium alloy bone scaffold proposed in this invention;

[0033] Figure 2 This is a photograph of the drug-loaded porous magnesium alloy bone scaffold prepared in Example 2 of the present invention.

[0034] Figure 3 The strength performance test diagrams of the drug-loaded porous magnesium alloy bone scaffolds prepared for the examples and comparative examples are shown.

[0035] Figure 4 In vitro corrosion test images of drug-loaded porous magnesium alloy bone scaffolds prepared for examples and comparative examples;

[0036] Figure 5 Antibiotic concentration detection graphs of drug-loaded porous magnesium alloy bone scaffolds prepared for examples and comparative examples;

[0037] Figure 6 The image shows the cell viability test results of the drug-loaded porous magnesium alloy bone scaffolds prepared for the examples and comparative examples.

[0038] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof. Detailed Implementation

[0039] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention. The preferred embodiments and materials described herein are for illustrative purposes only and do not limit the scope of this application.

[0041] The preparation methods, material distribution, and performance testing in the following examples are described with reference to... Figures 1-6 Unless otherwise specified, all methods are conventional. Unless otherwise specified, all parts of the materials used in the following examples are by weight. The magnesium alloy is a Mg-Zn based alloy with a Zn content of 3.5% and the remainder being Mg. The antibiotic is tetracycline. The drug-loaded porous magnesium alloy bone scaffold includes, from the inside out, magnesium alloy, gelatin, corrosion inhibitor and antibacterial bone-promoting agent. The magnesium alloy is filled with a drug-loaded gel.

[0042] Example 1: A drug-loaded porous magnesium alloy bone scaffold, composed of the following raw materials in parts by weight: 55 parts magnesium alloy, 6 parts corrosion inhibitor, 1 part drug-loaded gel, 2 parts antibacterial bone-promoting agent, and 3 parts gelatin;

[0043] The method for preparing drug-loaded gels includes the following steps:

[0044] A. Weigh 3 parts polylactic acid, 2.5 parts polycaprolactone and 1 part polyethylene glycol, mix them and heat them together in an oil bath at 120°C for 1 hour to obtain a copolymer. Then, rapidly cool it at -30°C for 24 hours, pulverize it with a pulverizer, and sieve it with a 100-mesh sieve to obtain fine copolymer particles.

[0045] B. Add the copolymer particles obtained in step A and 1 part of antibiotic to 10 parts of deionized water, stir for 30 min at a speed of 300 r / min, then add 2 parts of gel, lower the temperature to -10℃ and cure for 24 h, pulverize, and sieve using a 100 mesh screen to obtain the drug-loaded gel.

[0046] The method for preparing the corrosion-resistant material includes the following steps:

[0047] 1. Weigh 4 parts silk fibroin and 6 parts polycaprolactone, add 40 parts deionized water, sonicate for 30 min at a power of 0.5 kW, stir for 30 min at a speed of 300 r / min, centrifuge for 15 min at a speed of 5000 r / min to obtain a mixed solution, spin the obtained mixed solution under a working voltage of 15 kV and a receiving distance of 10 cm to obtain a fiber membrane;

[0048] 2. Weigh 5 parts of sodium alginate and add them to 15 parts of deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution A. Dip and deposit solution A onto the fiber membrane obtained in step 1 to obtain a composite membrane.

[0049] 3. Weigh 2 parts calcium chloride and 6 parts hydroxyapatite and add them to 25 parts deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution B. Atomize solution B and spray it onto the composite film obtained in step 2 to obtain the corrosion inhibitor precursor.

[0050] 4. The corrosion-resistant precursor obtained in step 3 is photothermally cured for 20 minutes under ultraviolet light at a wavelength of 280nm, at a distance of 15cm, to obtain the corrosion-resistant material.

[0051] The preparation method of the antibacterial bone-promoting substance includes the following steps:

[0052] (a) Weigh 3 parts of modified chitosan and add it to 30 parts of deionized water. Heat at 70°C for 2 hours and stir at 300 r / min for 30 minutes to obtain reaction solution I.

[0053] (b) Weigh 2.5 parts of poly-N-isopropylacrylamide and add it to the reaction solution I obtained in step (a). Stir at 300 r / min for 30 min. Then add 2 parts of hyaluronic acid and stir at 500 r / min for 30 min to obtain the complex. Freeze-dry the complex at -20℃ for 72 h to obtain the antibacterial bone-promoting substance.

[0054] The preparation method of modified chitosan includes the following steps:

[0055] (α) Weigh 5 parts of chitosan and add them to 30 parts of deionized water. Stir for 30 minutes at a speed of 500 r / min to obtain a solution.

[0056] (β) Weigh 3 parts of potassium dihydrogen phosphate and 0.8 parts of arginine and add them to the solution obtained in step (α). Stir for 30 minutes at a speed of 300 r / min to obtain the reaction solution.

[0057] (γ) The reaction solution obtained in step (β) was subjected to hydrothermal reaction at 90℃ for 6 h, naturally cooled to room temperature, centrifuged at 8000 r / min for 20 min, washed 5 times with deionized water, and then placed in a vacuum drying oven at 65℃ for 24 h to obtain modified chitosan.

[0058] This embodiment also provides a method for preparing a drug-loaded porous magnesium alloy bone scaffold, comprising the following steps:

[0059] Step 1. Weigh 55 parts of magnesium alloy and draw them at 0.3 m / min at 300℃ to obtain a 3 mm thick magnesium alloy tube. Then, drill holes in the magnesium alloy tube to a hole density of 280 holes / cm³. 2 Then, a 10μm magnesium oxide ceramic layer was grown in situ through micro-arc oxidation treatment, with a voltage of 450V, a frequency of 150Hz, and an oxidation time of 10min, resulting in a microporous filled tube with a pore size of 200μm.

[0060] Step 2. Weigh 1 part of the drug-loaded gel and fill it into the microporous filling tube obtained in Step 1, wherein the filling pressure is 0.5 MPa, and the filling tube is obtained.

[0061] Step 3. The filled tube obtained in Step 2 is subjected to laser texturing treatment with a wavelength of 1065nm and a texturing depth of 50μm to obtain a texturing composite magnesium alloy tube. 3 parts of gelatin are weighed and added to 3 parts of deionized water. The mixture is stirred for 10min at a speed of 500r / min to obtain a gelatin solution. The gelatin solution is deposited onto the surface of the texturing composite magnesium alloy tube to obtain an activated magnesium alloy tube.

[0062] Step 4. Weigh 6 portions of corrosion-resistant material and evenly apply them to the surface of the activated magnesium alloy pipe. Hot press for 20 minutes at a temperature of 180℃ and a pressure of 15MPa to obtain the corrosion-resistant magnesium alloy implant.

[0063] Step 5. Weigh 2 parts of antibacterial bone-promoting agent and add 5 parts of deionized water. Stir at 500 r / min for 30 min to obtain a mixture. Spray the mixture onto the surface of the corrosion-resistant magnesium alloy implant obtained in Step 4 with a spray thickness of 30 μm. Sterilize at 110℃ and 0.1 MPa for 30 min, and then allow it to cool naturally to room temperature to obtain a drug-loaded porous magnesium alloy bone scaffold.

[0064] Example 2: A drug-loaded porous magnesium alloy bone scaffold, composed of the following raw materials in parts by weight: 55 parts magnesium alloy, 8 parts corrosion inhibitor, 1 part drug-loaded gel, 3 parts antibacterial bone-promoting agent, and 3 parts gelatin;

[0065] The method for preparing drug-loaded gels includes the following steps:

[0066] A. Weigh 3.5 parts of polylactic acid, 3 parts of polycaprolactone and 1.5 parts of polyethylene glycol, mix them and heat them together in an oil bath at 135℃ for 1 hour to obtain a copolymer. Then, rapidly cool it at -30℃ for 24 hours, pulverize it with a pulverizer, and sieve it with a 100-mesh sieve to obtain fine copolymer particles.

[0067] B. Add the copolymer particles obtained in step A and 1 part of antibiotic to 10 parts of deionized water, stir for 30 min at a speed of 300 r / min, then add 2.5 parts of gel, lower the temperature to -10℃ and cure for 24 h, pulverize, and sieve using a 100 mesh screen to obtain the drug-loaded gel.

[0068] The method for preparing the corrosion-resistant material includes the following steps:

[0069] 1. Weigh 5.5 parts silk fibroin and 8 parts polycaprolactone, add them to 40 parts deionized water, sonicate for 30 minutes at a power of 0.5 kW, stir for 30 minutes at a speed of 300 r / min, centrifuge for 15 minutes at a speed of 5000 r / min to obtain a mixed solution, and spin the obtained mixed solution at a working voltage of 15 kV with a receiving distance of 10 cm to obtain a fiber membrane;

[0070] 2. Weigh 5 parts of sodium alginate and add them to 15 parts of deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution A. Dip and deposit solution A onto the fiber membrane obtained in step 1 to obtain a composite membrane.

[0071] 3. Weigh 3 parts calcium chloride and 7 parts hydroxyapatite and add them to 25 parts deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution B. Atomize solution B and spray it onto the composite film obtained in step 2 to obtain the corrosion inhibitor precursor.

[0072] 4. The corrosion-resistant precursor obtained in step 3 is photothermally cured for 20 minutes under ultraviolet light at a wavelength of 280nm, at a distance of 15cm, to obtain the corrosion-resistant material.

[0073] The preparation method of the antibacterial bone-promoting substance includes the following steps:

[0074] (a) Weigh 4.5 parts of modified chitosan and add it to 30 parts of deionized water. Heat at 70°C for 2 hours and stir at 300 r / min for 30 minutes to obtain reaction solution I.

[0075] (b) Weigh 3.5 parts of poly-N-isopropylacrylamide and add it to the reaction solution I obtained in step (a). Stir at 300 r / min for 30 min. Then add 2 parts of hyaluronic acid and stir at 500 r / min for 30 min to obtain the complex. Freeze-dry the complex at -20℃ for 72 h to obtain the antibacterial bone-promoting substance.

[0076] The preparation method of modified chitosan includes the following steps:

[0077] (α) Weigh 6.5 parts of chitosan and add it to 30 parts of deionized water. Stir for 30 minutes at a speed of 500 r / min to obtain a solution.

[0078] (β) Weigh 4 parts of potassium dihydrogen phosphate and 0.8 parts of arginine and add them to the solution obtained in step (α). Stir for 30 minutes at a speed of 300 r / min to obtain the reaction solution.

[0079] (γ) The reaction solution obtained in step (β) was subjected to hydrothermal reaction at 110℃ for 6 h, naturally cooled to room temperature, centrifuged at 8000 r / min for 20 min, washed 5 times with deionized water, and then placed in a vacuum drying oven at 65℃ for 24 h to obtain modified chitosan.

[0080] This embodiment also provides a method for preparing a drug-loaded porous magnesium alloy bone scaffold, comprising the following steps:

[0081] Step 1. Weigh 55 parts of magnesium alloy and draw them at 0.3 m / min at 300℃ to obtain a 3 mm thick magnesium alloy tube. Then, drill holes in the magnesium alloy tube to a hole density of 280 holes / cm³. 2 Then, a 10μm magnesium oxide ceramic layer was grown in situ through micro-arc oxidation treatment, with a voltage of 450V, a frequency of 150Hz, and an oxidation time of 10min, resulting in a microporous filled tube with a pore size of 200μm.

[0082] Step 2. Weigh 1 part of the drug-loaded gel and fill it into the microporous filling tube obtained in Step 1, wherein the filling pressure is 0.5 MPa, and the filling tube is obtained.

[0083] Step 3. The filled tube obtained in Step 2 is subjected to laser texturing treatment with a wavelength of 1065nm and a texturing depth of 50μm to obtain a texturing composite magnesium alloy tube. 3 parts of gelatin are weighed and added to 3 parts of deionized water. The mixture is stirred for 10min at a speed of 500r / min to obtain a gelatin solution. The gelatin solution is deposited onto the surface of the texturing composite magnesium alloy tube to obtain an activated magnesium alloy tube.

[0084] Step 4. Weigh 8 portions of corrosion-resistant material and evenly apply them to the surface of the activated magnesium alloy pipe. Hot press for 20 minutes at a temperature of 180-240℃ and a pressure of 15MPa to obtain the corrosion-resistant magnesium alloy implant.

[0085] Step 5. Weigh 3 parts of antibacterial bone-promoting agent and add 5 parts of deionized water. Stir at 500 r / min for 30 min to obtain a mixture. Spray the mixture onto the surface of the corrosion-resistant magnesium alloy implant obtained in Step 4 with a coating thickness of 30 μm. Sterilize at 110℃ and 0.1 MPa for 30 min, and then allow it to cool naturally to room temperature to obtain a drug-loaded porous magnesium alloy bone scaffold.

[0086] Example 3: A drug-loaded porous magnesium alloy bone scaffold, composed of the following raw materials in parts by weight: 55 parts magnesium alloy, 10 parts corrosion inhibitor, 1 part drug-loaded gel, 4 parts antibacterial bone-promoting agent, and 3 parts gelatin;

[0087] The method for preparing drug-loaded gels includes the following steps:

[0088] A. Weigh 4 parts polylactic acid, 3.5 parts polycaprolactone and 2 parts polyethylene glycol, mix them and heat them together in an oil bath at 150℃ for 1 hour to obtain a copolymer. Then, rapidly cool it at -30℃ for 24 hours, pulverize it with a pulverizer, and sieve it with a 100-mesh sieve to obtain fine copolymer particles.

[0089] B. Add the copolymer particles obtained in step A and 1 part of antibiotic to 10 parts of deionized water, stir for 30 min at a speed of 300 r / min, then add 3 parts of gel, lower the temperature to -10℃ and cure for 24 h, pulverize, and sieve using a 100 mesh screen to obtain the drug-loaded gel.

[0090] The method for preparing the corrosion-resistant material includes the following steps:

[0091] 1. Weigh 7 parts silk fibroin and 10 parts polycaprolactone, add 40 parts deionized water, sonicate for 30 min at a power of 0.5 kW, stir for 30 min at a speed of 300 r / min, centrifuge for 15 min at a speed of 5000 r / min to obtain a mixed solution, spin the obtained mixed solution under a working voltage of 15 kV and a receiving distance of 10 cm to obtain a fiber membrane;

[0092] 2. Weigh 5 parts of sodium alginate and add them to 15 parts of deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution A. Dip and deposit solution A onto the fiber membrane obtained in step 1 to obtain a composite membrane.

[0093] 3. Weigh 4 parts calcium chloride and 8 parts hydroxyapatite and add them to 25 parts deionized water. Stir for 30 minutes at a speed of 300 r / min to obtain solution B. Atomize solution B and spray it onto the composite film obtained in step 2 to obtain the corrosion inhibitor precursor.

[0094] 4. The corrosion-resistant precursor obtained in step 3 is photothermally cured for 20 minutes under ultraviolet light at a wavelength of 280nm, at a distance of 15cm, to obtain the corrosion-resistant material.

[0095] The preparation method of the antibacterial bone-promoting substance includes the following steps:

[0096] (a) Weigh 6 parts of modified chitosan and add it to 30 parts of deionized water. Heat at 70°C for 2 hours and stir at 300 r / min for 30 minutes to obtain reaction solution I.

[0097] (b) Weigh 4.5 parts of poly-N-isopropylacrylamide and add it to the reaction solution I obtained in step (a). Stir at 300 r / min for 30 min. Then add 2 parts of hyaluronic acid and stir at 500 r / min for 30 min to obtain the complex. Freeze-dry the complex at -20℃ for 72 h to obtain the antibacterial bone-promoting substance.

[0098] The preparation method of modified chitosan includes the following steps:

[0099] (α) Weigh 8 parts of chitosan and add it to 30 parts of deionized water. Stir for 30 minutes at a speed of 500 r / min to obtain a solution.

[0100] (β) Weigh 5 parts of potassium dihydrogen phosphate and 0.8 parts of arginine and add them to the solution obtained in step (α). Stir for 30 minutes at a speed of 300 r / min to obtain the reaction solution.

[0101] (γ) The reaction solution obtained in step (β) was subjected to hydrothermal reaction at 120℃ for 6 h, naturally cooled to room temperature, centrifuged at 8000 r / min for 20 min, washed 5 times with deionized water, and then placed in a vacuum drying oven at 65℃ for 24 h to obtain modified chitosan.

[0102] This embodiment also provides a method for preparing a drug-loaded porous magnesium alloy bone scaffold, comprising the following steps:

[0103] Step 1. Weigh 55 parts of magnesium alloy and draw them at 0.3 m / min at 300℃ to obtain a 3 mm thick magnesium alloy tube. Then, drill holes in the magnesium alloy tube to a hole density of 280 holes / cm³. 2 Then, a 10μm magnesium oxide ceramic layer was grown in situ through micro-arc oxidation treatment, with a voltage of 450V, a frequency of 150Hz, and an oxidation time of 10min, resulting in a microporous filled tube with a pore size of 200μm.

[0104] Step 2. Weigh 1 part of the drug-loaded gel and fill it into the microporous filling tube obtained in Step 1, wherein the filling pressure is 0.5 MPa, and the filling tube is obtained.

[0105] Step 3. The filled tube obtained in Step 2 is subjected to laser texturing treatment with a wavelength of 1065nm and a texturing depth of 50μm to obtain a texturing composite magnesium alloy tube. 3 parts of gelatin are weighed and added to 3 parts of deionized water. The mixture is stirred for 10min at a speed of 500r / min to obtain a gelatin solution. The gelatin solution is deposited onto the surface of the texturing composite magnesium alloy tube to obtain an activated magnesium alloy tube.

[0106] Step 4. Weigh 10 parts of the corrosion-resistant material and evenly apply it to the surface of the activated magnesium alloy pipe. Hot press it for 20 minutes at a temperature of 240℃ and a pressure of 15MPa to obtain the corrosion-resistant magnesium alloy implant.

[0107] Step 5. Weigh 4 parts of antibacterial bone-promoting agent and add 5 parts of deionized water. Stir at 500 r / min for 30 min to obtain a mixture. Spray the mixture onto the surface of the corrosion-resistant magnesium alloy implant obtained in Step 4 with a spray thickness of 30 μm. Sterilize at 110℃ and 0.1 MPa for 30 min, and then allow it to cool naturally to room temperature to obtain a drug-loaded porous magnesium alloy bone scaffold.

[0108] Comparative Example: The difference between Comparative Example 1 and Example 2 is that no corrosion inhibitor was added; the rest of the parts are the same as Example 2.

[0109] The difference between Comparative Example 2 and Example 2 is that no drug gel was loaded; the rest is the same as Example 2.

[0110] The difference between Comparative Example 3 and Example 2 is that gelatin was not added; the rest of the parts are the same as Example 2.

[0111] To test the strength and corrosion resistance of the prepared drug-loaded porous magnesium alloy bone scaffold, strength tests were conducted according to GB / T16865-2023. The results are as follows: Figure 3 As shown, the drug-loaded porous magnesium alloy bone scaffold prepared in Example 2 has a yield strength of 246 MPa and a tensile strength of 268 MPa, indicating superior material strength compared to the comparative example. To verify the corrosivity of the prepared drug-loaded porous magnesium alloy bone scaffold, a solution identical to the body fluid environment was prepared. To ensure an effective simulated environment, the solution was changed every 10 days. The prepared drug-loaded porous magnesium alloy bone scaffold was completely immersed in the prepared solution, and the solution was kept at a constant temperature of 36.5 ± 0.2 °C. The scaffold was placed in a sterile, sealed environment, and corrosion was monitored periodically. The test results are as follows: Figure 4 As shown, in Example 2, the corrosion thickness was 5.7 μm in the 0-1 month stage, 8.1 μm in the 2-3 month stage, 11.3 μm in the 4-6 month stage, and 9.7 μm in the 7-12 month stage, indicating that the prepared drug-loaded porous magnesium alloy bone scaffold has strong corrosion resistance.

[0112] To further verify the antibiotic release after loading, drug-loaded porous magnesium alloy bone scaffolds with a length of 6-8 mm were prepared according to actual needs, with a treatment cycle of 6 months. The corrosion-resistant material of the drug-loaded porous magnesium alloy bone scaffold was 30-35 μm thick. The antibiotic concentration was further tested by placing a 1 cm section of the drug-loaded porous magnesium alloy bone scaffold into 10 mL of prepared simulated body fluid and maintaining it at 36.5℃. The fluid flow was simulated by oscillation at a frequency of 60 r / min. Samples were taken and tested at 7, 14, 28, 56, 84, and 112 days under sterile conditions. Specific test results are as follows: Figure 5 As shown, the concentration of released antibiotics gradually increases with increasing test time, indicating that the antibiotic release process can effectively achieve a sustained-release effect. To verify the cell compatibility of the drug-loaded porous magnesium alloy bone scaffold, a cell viability test was performed (standard reference ISO 10993-5, method reference MTT assay). Specific results are shown below. Figure 6 As shown, the drug-loaded porous magnesium alloy bone scaffolds prepared in the examples and comparative examples both exhibit good cellular characterization and low overall toxicity to cells.

[0113] Table 1 shows the statistical results of the degradation of drug-loaded porous magnesium alloy bone scaffolds implanted in mouse models:

[0114]

[0115] As shown in Table 1, the surface coating of the prepared drug-loaded porous magnesium alloy bone scaffold completely decomposed after 6 months, and then the internal magnesium alloy began to degrade, indicating that the prepared material has good implantability.

[0116] Obviously, the above comparative examples and embodiments are only a part of the comparative examples and embodiments of the present invention, and they, along with the comparative examples and embodiments referenced based on such examples, are all within the scope of protection of this invention.

[0117] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0118] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention. The actual application is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar methods and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A drug-loaded porous magnesium alloy bone scaffold, characterized in that, From the inside out, it includes magnesium alloy, gelatin, corrosion inhibitor, and antibacterial bone-promoting agent. The magnesium alloy is filled with a drug-loaded gel. The mass proportions of the above materials are as follows: 55 parts magnesium alloy, 6-10 parts corrosion inhibitor, 1 part drug-loaded gel, 2-4 parts antibacterial bone-promoting agent, and 3 parts gelatin. The drug-loaded gel comprises the following raw materials in the following mass ratio: polylactic acid, polycaprolactone, polyethylene glycol, gel and antibiotic = 3-4: 2.5-3.5: 1-2: 2-3: 1; The corrosion-resistant material comprises the following raw materials in the following mass ratio: silk protein, sodium alginate, polycaprolactone, hydroxyapatite and calcium chloride = 4-7:5:6-10:6-8:2-4; The antibacterial bone-promoting compound comprises the following raw materials in the following mass ratio: modified chitosan, poly-N-isopropylacrylamide, and hyaluronic acid = 3-6:2.5-4.5:

2.

2. The drug-loaded porous magnesium alloy bone scaffold according to claim 1, characterized in that, The method for preparing the drug-loaded gel includes the following steps: A. Polylactic acid, polycaprolactone, and polyethylene glycol are heated together to obtain a copolymer, which is then pulverized to obtain fine copolymer particles; B. Add copolymer particles and antibiotics to water, stir, add gel, solidify, pulverize, and obtain drug-loaded gel.

3. The drug-loaded porous magnesium alloy bone scaffold according to claim 1, characterized in that, The method for preparing the corrosion-resistant material includes the following steps: I. Weigh silk fibroin and polycaprolactone, add them to water, sonicate and stir, centrifuge to obtain a mixed solution, spin the mixed solution to obtain a fiber membrane; II. Sodium alginate is added to water and stirred to obtain solution A. Solution A is deposited on the fiber membrane to obtain a composite membrane. III. Add calcium chloride and hydroxyapatite to water and stir to obtain solution B. Spray solution B onto the composite membrane to obtain the corrosion inhibitor precursor. VI. By solidifying the precursor of the anti-corrosion agent, an anti-corrosion agent is obtained.

4. The drug-loaded porous magnesium alloy bone scaffold according to claim 1, characterized in that, The method for preparing the antibacterial bone-promoting substance includes the following steps: (a) Add the modified chitosan to water, heat and stir to obtain reaction solution I; (b) Poly(N-isopropylacrylamide) was added to reaction solution I and stirred. Then hyaluronic acid was added and stirred to obtain a complex. The complex was dried to obtain an antibacterial bone-promoting substance.

5. The drug-loaded porous magnesium alloy bone scaffold according to claim 4, characterized in that, The modified chitosan comprises the following raw materials in the following mass ratio: chitosan, potassium dihydrogen phosphate and arginine = 5-8:3-5:0.8; The method for preparing the modified chitosan includes the following steps: (α) Add chitosan to water and stir to obtain a solution; (β) Add potassium dihydrogen phosphate and arginine to the solution, stir, and obtain the reaction solution; (γ) The reaction solution was heated, cooled, centrifuged, washed and dried to obtain modified chitosan.

6. A method for preparing a drug-loaded porous magnesium alloy bone scaffold as described in any one of claims 1-5, characterized in that, Includes the following steps: Step 1. The magnesium alloy is extruded and drawn to obtain a solid magnesium alloy tube. The solid magnesium alloy tube is then perforated and subjected to micro-arc oxidation to obtain a micro-pore filled tube. Step 2. Weigh the drug-loaded gel and fill it into the microporous filling tube to obtain the filling tube; Step 3. The filling tube is roughened to obtain roughened composite magnesium alloy tube. Gelatin is added to water and stirred to obtain a gelatin solution. The gelatin solution is deposited onto the surface of the roughened composite magnesium alloy tube to obtain activated magnesium alloy tube. Step 4. Weigh the corrosion-resistant material and apply it evenly to the surface of the activated magnesium alloy pipe, then hot-press it to obtain the corrosion-resistant magnesium alloy implant. Step 5. Weigh the antibacterial bone-promoting agent and add it to water, stir to obtain a mixture, spray the mixture onto the surface of the corrosion-resistant magnesium alloy implant, sterilize, cool, and obtain a drug-loaded porous magnesium alloy bone scaffold.

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