Finished product of 3D-printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone, preparation method and application

Abstract

The invention relates to the technical field of medical consumables, in particular to a finished product of a 3D-printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone as well as a preparation method and application of the finished product of the 3D-printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone. The finished product of the 3D printing PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone comprises a hydroxyapatite / calcium silicate ceramic artificial bone and a PaMZ / PLGA slow-release system, and can effectively and slowly release antituberculosis drugs for sterilization for a long time, so that spinal tuberculosis is thoroughly treated. The drug-loaded artificial bone material disclosed by the invention can be applied to filling of bone defect parts of spinal tuberculosis, so that the practical problem that hydroxyapatite ceramic artificial bones are relatively low in strength is solved, and the problem that the blood concentration of the bone defect parts of spinal tuberculosis is relatively low is also solved, and thus the cure rate of spinal tuberculosis is increased.

Description

Technical Field

[0001] The present invention relates to the technical field of medical consumables, and in particular to a finished product, a preparation method and application of a 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone. Background Art

[0002] Tuberculosis is an ancient and serious disease that is harmful to the human body. In 2019 alone, 10 million new cases of tuberculosis were reported worldwide. In addition to the lungs, the spine is also often affected. The spine is the most common site of bone tuberculosis, which often leads to serious complications such as spinal destruction and spinal cord compression. Bone destruction caused by spinal tuberculosis and obstruction of tuberculosis foci by sclerotic walls are two difficult problems in the treatment of spinal tuberculosis. The presence of sclerotic walls blocks the entry of anti-tuberculosis drugs, making the drug concentration in the lesion far lower than the normal blood drug concentration. The huge bone destruction caused by spinal tuberculosis requires bone grafting. Autologous iliac bone is the best bone graft material, but there are many postoperative complications such as iliac bone fractures; allogeneic bone has the risk of donor disease transmission, and animal-derived bones often have fractures that do not heal due to the problem of high immunogenicity. The development of bone tissue engineering has provided new possibilities for the treatment of bone defects in spinal tuberculosis. Hydroxyapatite is the main component of human bones and is an ideal material for preparing ceramic artificial bones. However, the strength of simply printed hydroxyapatite artificial bones is low. The maximum compressive strength of 3D-printed artificial bones is 6.25Mpa, which only reaches the level of cancellous bone. The strength reported in the literature usually does not exceed 10Mpa, which makes it difficult to meet the requirements of structural bone grafting after the removal of spinal tuberculosis lesions. How to further improve the strength of drug-loaded artificial bones to meet the requirements of spinal structural bone grafting is an urgent problem that needs to be solved. The literature reports that the strength of single hydroxyapatite artificial bones is insufficient, and the strength of the material can be increased after adding calcium silicate. Calcium silicate degrades and deposits on hydroxyapatite under physiological conditions. Degradation can release silicon ions and calcium ions to promote bone cell proliferation. The resulting porous structure also provides conditions for the proliferation and attachment of bone cells, but this mixed material simply printed at room temperature is still insufficient in strength.

[0003] Drug resistance of bone tuberculosis is also one of the difficulties faced by current treatment. Relevant studies have shown that drug resistance of spinal tuberculosis in India has reached 28%, among which isoniazid resistance is the most common. Delamanid is a Pa-824 compound, a nitrodihydroimidazooxazole derivative, with an in vitro minimum inhibitory concentration (MIC) of 0.001-0.05 mg / L for the standard strain H37Rv. From 2012 to 2022, prospective, randomized studies in several top journals showed that Pa-824 drugs combined with moxifloxacin and pyrazinamide showed excellent anti-tuberculosis performance and good tolerability against drug-resistant tuberculosis bacteria, and it is expected to shorten the course of treatment. Local sustained-release system refers to the use of degradable polymers such as chitosan, gelatin, polylactic acid, etc. as carriers. The drug can be released to a specific site through a membrane or matrix to control diffusion and achieve long-term, sufficient and stable release. Polylactic-co-glycolic acid (PLGA) is a biodegradable polymer that plays an important role in sustained-release systems. PLGA has a wide range of degradation times and is soluble in common solvents. Its degradation time can be adjusted according to its molecular weight and copolymer ratio. In addition, as a carrier for sustained-release drugs, PLGA can be plasticized according to the different shapes and requirements of the stent, such as size, shape, surface area to volume ratio, etc., which can all be "adjusted". Most importantly, PLGA has good biocompatibility and release properties, and has been approved by the US Food and Drug Administration for human use. It has been widely used in pharmaceutical and food fields. However, how to encapsulate the latest anti-tuberculosis drugs and release them in long-term and sufficient amounts is one of the current difficulties.

[0004] Therefore, it is an urgent problem for technicians in this field to develop a 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone and preparation method that has high strength, can be mass-produced, and can release drugs in a long-term, sufficient, and stable manner. Summary of the invention

[0005] In view of this, in order to solve the above technical problems, the present invention discloses a finished product, a preparation method and application of a 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone.

[0006] In order to achieve the above object, the present invention adopts the following technical solution:

[0007] The first technical purpose of the present invention is to provide a finished product of 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone, including hydroxyapatite / calcium silicate ceramic artificial bone and PaMZ / PLGA sustained-release system; wherein,

[0008] The mass ratio of hydroxyapatite to calcium silicate in the hydroxyapatite / calcium silicate ceramic artificial bone is 6:4; the hydroxyapatite includes nano-hydroxyapatite and hydroxyapatite whiskers; the compressive strength of the hydroxyapatite / calcium silicate ceramic artificial bone after firing is 20.55±1.90Mpa, and the maximum compressive strength can reach 21.89Mpa; the layer thickness of the hydroxyapatite / calcium silicate ceramic artificial bone is 200um, and the porosity is 40.3±0.5%; through the reasonable ratio of nano-hydroxyapatite and calcium silicate, after firing, not only the compressive strength of the scaffold is increased, but also the released Si 2+ / Ca 2+ , which can promote bone regeneration.

[0009] The PaMZ / PLGA sustained-release system contains the latest anti-tuberculosis drug Pa, drug M, drug Z, and sustained-release agent PLGA; the optimal release mass ratio in the PaMZ / PLGA sustained-release system is delamanid (Pa): moxifloxacin (M): pyrazinamide (Z): polylactic acid glycolic acid (PLGA) = 3:12:45:140; the maximum sustained-release time in the PaMZ / PLGA sustained-release system can reach 70 days. The latest anti-tuberculosis drug regimen can effectively kill bacteria in spinal tuberculosis bone defect sites, thereby accelerating the healing of bone defect sites.

[0010] The beneficial effect of adopting the above technical scheme is that in the present invention, hydroxyapatite / calcium silicate ceramic artificial bone is first printed and fired to greatly improve the compressive strength and stability of the scaffold, and then the anti-tuberculosis drug is loaded on the surface of the scaffold through the PaMZ / PLGA sustained-release system to achieve a sufficient anti-tuberculosis effect; because the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone has good compressive strength and structural stability, it has a good supporting effect on the spinal tuberculosis bone defect; at the same time, the loaded anti-tuberculosis drug can effectively kill the Mycobacterium tuberculosis in the sclerotic bone in the tuberculosis bone defect, and promote the healing of the bone defect.

[0011] The second technical purpose of the present invention is to provide a method for preparing a finished product of the 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone as described above, characterized in that the method specifically comprises the following steps:

[0012] 1) Model design: Design the layer thickness in the Solidwork software to be 200um, length*width*height=1*1*1cm 3 , a cube model with a filling rate of 60% and a porosity of 40%, and then imported into Magics for preprocessing;

[0013] 2) Preparation of hydroxyapatite / calcium silicate ceramic artificial bone scaffold: According to the mass ratio of nanohydroxyapatite: calcium silicate = 6:4, accurately weigh 19.2g of nanohydroxyapatite, 4.8g of hydroxyapatite whiskers, 16g of calcium silicate, and 28.4g of 8% polyvinyl alcohol aqueous solution, dissolve in a 97℃ water bath to prepare 8% polyvinyl alcohol aqueous solution, and then mix and stir the weighed three materials; after homogenization, a uniform printing slurry is obtained, which is loaded into a dispensing syringe and degassed for 20 minutes before use; the degassed printing slurry is placed on a bioceramic 3D printer for printing, and the printing speed is set to 10mm / s, the layer height is 200μm, and the filling rate is 60%. After printing is completed and freeze-dried, it is then sintered at 1300℃ for 3 hours, cooled to 900℃ and kept warm for 2 hours, and cooled to room temperature by itself to obtain a bioceramic artificial bone material;

[0014] 3) Preparation of PaMZ / PLGA sustained-release system: 1.33 mg of Pa was weighed and dissolved in acetone, 7.71 mg of M and 28.93 mg of Z were dissolved in anhydrous ethanol, and 90 mg of PLGA was dissolved in dichloromethane according to the mass ratio of 3:12:45:140, and vortexed to accelerate dissolution; the magnetic stirrer was set at 70°C and 30 r / min, and Pa and M / Z solutions were added first and mixed, and then PLGA was added and vortexed until the solution was completely transparent;

[0015] 4) Preparation of 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone: Place the 3D printed ceramic artificial bone scaffold into a completely transparent PaMZ / PLGA sustained-release system, continue heating and volatilization, and dissolve until PLGA is completely attached to the surface of the ceramic artificial bone. Take out the drug-loaded ceramic artificial bone and dry it in a negative pressure fume hood to obtain the finished product of the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone.

[0016] The third technical purpose of the present invention is to provide the application of the finished product of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone prepared by the method as described above in medical consumables.

[0017] Specifically, the finished product of the 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone can be used as a medical consumable for treating spinal tuberculosis.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] (1) The hydroxyapatite / calcium silicate ceramic artificial bone prepared by 3D printing and high temperature firing in the present invention has good structural stability, and its maximum compressive strength can reach 21.89 MPa, which can meet the application of non-load-bearing bone defects; the Si released by the combined use of nano-hydroxyapatite / calcium silicate 2+ / Ca2+ Can promote bone regeneration;

[0020] (2) The PaMZ / PLGA sustained-release system prepared in the present invention can release anti-tuberculosis drugs for a long time, in sufficient quantity and stably, achieving a good bactericidal effect. The maximum sustained-release time can reach 70 days, which can accelerate the killing of bacteria in tuberculosis bone defect sites. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying creative work.

[0022] Figure 1 A schematic diagram of the structure of the 3D printed hydroxyapatite / calcium silicate ceramic artificial bone provided by the present invention;

[0023] Figure 2 A schematic diagram of the structure of the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone (hereinafter referred to as drug-loaded artificial bone) provided by the present invention;

[0024] Figure 3 Determination of porosity and compressive strength of the drug-loaded artificial bone provided by the present invention;

[0025] Figure 4 The drug release time and curve of the drug-loaded artificial bone provided by the present invention;

[0026] Figure 5 A schematic diagram of the co-culture of the drug-loaded artificial bone provided by the present invention and standard Mycobacterium tuberculosis;

[0027] Figure 6 A schematic diagram of the co-culture of drug-loaded artificial bone and bone marrow mesenchymal stem cells provided by the present invention;

[0028] Figure 7 A schematic diagram of ALP osteogenic staining of the co-culture of drug-loaded artificial bone and bone marrow mesenchymal stem cells provided by the present invention;

[0029] Figure 8 A schematic diagram of ARS osteogenic staining of the drug-loaded artificial bone co-cultured with bone marrow mesenchymal stem cells provided by the present invention;

[0030] Fig. 9 A CT schematic diagram of osteogenesis of the drug-loaded artificial bone provided by the present invention in an animal body;

[0031] Fig.10 A schematic diagram of osteogenesis of the drug-loaded artificial bone provided by the present invention in an animal body;

[0032] Fig.11 A schematic diagram of HE staining of osteogenesis of the drug-loaded artificial bone provided by the present invention in an animal body;

[0033] Fig.12 This is a schematic diagram of toluidine blue staining of the osteogenesis of the drug-loaded artificial bone provided by the present invention in an animal body. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] The word "embodiment" used here as an "exemplary" does not necessarily mean that any embodiment described is superior to or better than other embodiments. Unless otherwise specified, the performance index tests in the embodiments of this application are performed using conventional test methods in the art. It should be understood that the terms described in this application are only used to describe specific implementation methods and are not used to limit the content disclosed in this application.

[0036] Unless otherwise specified, the technical and scientific terms used in this document have the same meanings as commonly understood by ordinary technicians in the technical field to which this application belongs; other experimental methods and technical means not specifically specified in this application refer to experimental methods and technical means commonly used by ordinary technicians in this field.

[0037] In the description of the present invention, it is necessary to understand that the terms "middle", "upper", "lower", "ascending", "descending", "vertical", "face", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship are based on the orientation or position relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0038] In order to better illustrate the content of the present application, numerous specific details are provided in the specific examples below. It should be understood by those skilled in the art that the present application can also be implemented without certain specific details. In the embodiments, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail in order to highlight the main purpose of the present application.

[0039] Under the premise of no conflict, the technical features disclosed in the embodiments of the present application can be combined arbitrarily, and the resulting technical solutions belong to the contents disclosed in the embodiments of the present application.

[0040] The invention discloses a finished product of a 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone for treating spinal tuberculosis and a preparation method thereof.

[0041] Example 1

[0042] The embodiment of the present invention discloses a 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone for treating spinal tuberculosis.

[0043] Through experimental optimization and screening, it was found that in the preparation experiment of artificial bone, after comparing the mass ratios of nano-hydroxyapatite / calcium silicate including 9:1 / 8:2 / 7:3 / 6:4, the compressive strength of the first three ratios was measured to be lower than 15Mpa, while the highest compressive strength of the 6:4 ratio reached 21.89Mpa, and the mass ratio of 6:4 with the highest compressive strength was obtained. Combined with previous literature, its optimal mass ratio and compressive strength were obtained; in the PaMZ / PLGA sustained-release system, through the preliminary orthogonal factorial experiment, the drug ratio of 6:12:45:95 / 4:12:45:244 / 3:12:45:140 and the scaffold pore size of 200 / 400 / 600um were selected, and finally the drug ratio of 3:12:45:140 with the longest drug release time was obtained, and the optimal pore size was 200um.

[0044] In this embodiment, the specific preparation method is as follows:

[0045] 1) Model design: Design the layer thickness in the Solidwork software to be 200um, length*width*height=1*1*1cm 3 , a cube model with a filling rate of 60% and a porosity of 40%, and then imported into Magics for preprocessing;

[0046] 2) Preparation of hydroxyapatite / calcium silicate ceramic artificial bone scaffold: 19.2 g of nano-hydroxyapatite, 4.8 g of hydroxyapatite whiskers, 16 g of calcium silicate, and 28.4 g of 8% polyvinyl alcohol aqueous solution were accurately weighed, and then dissolved in a 97°C water bath to prepare an 8% polyvinyl alcohol aqueous solution, and the weighed nano-hydroxyapatite, hydroxyapatite whiskers and calcium silicate were mixed, and the ingredients were homogenized and stirred; after homogenization, a uniform printing slurry was obtained, which was loaded into a dispensing syringe and degassed in a degassing machine for 20 minutes. Set aside; place the degassed printing slurry in a bioceramic 3D printer cartridge, set the printing speed to 10 mm / s, the layer height to 200 μm, the filling rate to 60%, and the porosity to 40%; after printing, transfer the scaffold to an in-situ freeze dryer, set the freeze drying temperature to -30°C, and take it out after freeze drying for later use; place the freeze-dried artificial bone scaffold in a box-type sintering furnace, set the temperature and time, sinter at 1300°C for 3 hours, cool to 900°C and keep warm for 2 hours, and cool to room temperature to obtain a high-strength hydroxyapatite / calcium silicate ceramic artificial bone;

[0047] 3) Preparation of PaMZ / PLGA sustained-release system: 1.33 mg of delamanid (Pa) was weighed and dissolved in acetone, 7.71 mg of M and 28.93 mg of Z were dissolved in anhydrous ethanol, and 90 mg of PLGA was dissolved in dichloromethane according to the mass ratio of 3:12:45:140, and vortexed to accelerate dissolution; the magnetic stirrer was set at 70°C and 30 r / min, and Pa and M / Z solutions were added first and mixed, and then PLGA was added and vortexed until the solution was completely transparent;

[0048] 4) Preparation of 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone: Place the 3D printed ceramic artificial bone scaffold into a completely transparent PaMZ / PLGA sustained-release system, continue heating and volatilization, and dissolve until PLGA is completely attached to the surface of the ceramic artificial bone. Take out the drug-loaded ceramic artificial bone and dry it in a negative pressure fume hood to obtain the finished product of the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone.

[0049] The compressive strength of the hydroxyapatite / calcium silicate ceramic artificial bone after firing is 20.55±1.90Mpa, and the maximum compressive strength can reach 21.89Mpa; the layer thickness of the hydroxyapatite / calcium silicate ceramic artificial bone is 200um, and the porosity is 40.3±0.5%; after the hydroxyapatite / calcium silicate ceramic artificial bone is loaded with the PaMZ / PLGA sustained-release system, the porosity can still reach 30.6±0.7%, and the maximum compressive strength reaches 17.65±0.46Mpa.

[0050] In order to further demonstrate the beneficial effects of the present invention and to better understand the present invention, the following experimental examples are used to further illustrate the technical features disclosed in the present invention, but they should not be understood as limiting the present invention. Other improvements made by those skilled in the art based on the above invention content without creative work are also considered to fall within the scope of protection of the present invention.

[0051] Combined with the technical follow-up of this case Figure 1-Figure 2 It can be clearly observed that the 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone provided by the present invention has a good cubic structure, and its good compressive resistance and pores help it promote the repair of fracture sites. Figure 5 It can be observed that the drug has an effective inhibitory effect on Mycobacterium tuberculosis, which directly demonstrates the anti-tuberculosis effect of the PaMZ / PLGA sustained-release system. Figure 4-Figure 10 The good osteogenic properties are demonstrated from different perspectives, especially Figure 7 The imaging CT in the image more intuitively shows the osteogenic properties of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bones. Effective osteogenesis is the key to the treatment of spinal tuberculosis.

[0052] Specifically, Figure 3 As shown, the mechanical properties were tested using an electronic universal tensile testing machine. The results showed that the porosity of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone could still reach 30.6±0.7%, and the maximum compressive strength reached 17.65±0.46Mpa, which had good compressive resistance and pore structure.

[0053] like Figure 4 As shown, the maximum release time of three anti-tuberculosis drugs detected by HPLC can reach 70 days.

[0054] like Figure 5 As shown, a cell co-culture experiment was used to verify the anti-tuberculosis property of its sustained-release terminal, indicating that it has good anti-tuberculosis property.

[0055] like Figure 6-8 As shown, the in vitro mesenchymal stem cell co-culture experiment / alkaline phosphatase staining experiment (ALP) / Alizarin red staining experiment (ARS) and other experiments were used to verify that the artificial bone has good in vitro osteogenic properties.

[0056] like Figure 9-12 As shown, the good in vivo bone-forming properties of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bones were verified by using experiments such as in vivo implantation experiments in rabbits / gross observations / HE staining experiments / toluidine blue staining experiments.

[0057] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A finished product of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone, characterized in that: It includes hydroxyapatite / calcium silicate ceramic artificial bone and PaMZ / PLGA sustained-release system; among which, The mass ratio of hydroxyapatite to calcium silicate in the hydroxyapatite / calcium silicate ceramic artificial bone is 6:4; The PaMZ / PLGA sustained-release system comprises an anti-tuberculosis drug Pa, a drug M, a drug Z, and a sustained-release agent PLGA; the optimal release mass ratio in the PaMZ / PLGA sustained-release system is Pa:M:Z:PLGA=3:12:45:

140.

2. The finished product of a 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone according to claim 1, characterized in that: The hydroxyapatite includes nano-hydroxyapatite and hydroxyapatite whiskers.

3. A method for preparing a finished product of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone as claimed in claim 2, characterized in that: The method specifically comprises the following steps: 1) Model design: Design the layer thickness in the Solidwork software to be 200um, length*width*height=1*1*1cm 3 , a cube model with a filling rate of 60% and a porosity of 40%, and then imported into Magics for preprocessing; 2) Preparation of hydroxyapatite / calcium silicate ceramic artificial bone scaffold: according to the mass ratio of hydroxyapatite: calcium silicate = 6:4, accurately weigh 19.2g of nano-hydroxyapatite, 4.8g of hydroxyapatite whiskers, 16g of calcium silicate, and 28.4g of 8% polyvinyl alcohol aqueous solution, dissolve in a 97°C water bath to prepare an 8% polyvinyl alcohol aqueous solution, and then mix and stir the weighed three materials; after homogenization, a uniform printing slurry is obtained, which is loaded into a dispensing syringe and degassed for 20 minutes for use; the degassed printing slurry is placed on a bioceramic 3D printer for printing, and the printing speed is set to 10mm / s, the layer height is 200μm, and the filling rate is 60%. After printing, it is freeze-dried, and then sintered at 1300°C for 3 hours, cooled to 900°C and kept warm for 2 hours, and cooled to room temperature by itself to obtain a bioceramic artificial bone material; 3) Preparation of PaMZ / PLGA sustained-release system: 1.33 mg of Pa was weighed and dissolved in acetone, 7.71 mg of M and 28.93 mg of Z were dissolved in anhydrous ethanol, and 90 mg of PLGA was dissolved in dichloromethane according to the mass ratio of 3:12:45:140, and vortexed to accelerate dissolution; the magnetic stirrer was set at 70°C and 30 r / min, and Pa and M / Z solutions were added first and mixed, and then PLGA was added and vortexed until the solution was completely transparent; 4) Preparation of 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone: Place the 3D printed ceramic artificial bone scaffold into a completely transparent PaMZ / PLGA sustained-release system, continue heating and volatilization, and dissolve until PLGA is completely attached to the surface of the ceramic artificial bone. Take out the drug-loaded ceramic artificial bone and dry it in a negative pressure fume hood to obtain the finished product of the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone.

4. Use of the finished product of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone as claimed in claim 2 or the finished product of 3D printed PaMZ / PLGA hydroxyapatite / calcium silicate ceramic artificial bone prepared by the method as claimed in claim 3 in medical consumables.

5. The use according to claim 4, characterized in that: The finished product of the 3D printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone can be used as a medical consumable for treating spinal tuberculosis.

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