3D printing drug-containing degradable magnesium alloy bone plate and preparation method thereof

Abstract

The present application relates to a kind of 3D printing band medicine degradable magnesium alloy bone plate and its preparation method, belong to biomedical technology field.The present application 3D printing band medicine degradable magnesium alloy bone plate, including degradable magnesium alloy base plate and the protective layer covered in base plate surface;The base plate is opened with porous structure, and the porous structure includes fixed hole, medicine hole and article hole;The medicine hole is used to carry drug;Article hole is installed transient electronic device, for monitoring the tissue condition of the injured part around bone plate;The protective layer is a kind of composite film layer, including antibacterial LDH film and tannin acid film;The composite film layer has good biocompatibility, simultaneously has very good protective effect, can greatly reduce the degradation rate of magnesium alloy, makes the service time of bone plate in human body extension, and can also play the role of sterilization.The preparation method of the present application 3D printing band medicine degradable magnesium alloy bone plate can quickly and accurately prepare band medicine degradable magnesium alloy bone plate suitable for the individual needs of different patients.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to a 3D-printed drug-eluting biodegradable magnesium alloy bone plate and its preparation method. Background Technology

[0002] Magnesium alloys possess characteristics similar to human bone, including specific stiffness, specific strength, and Young's modulus (E=41-45 GPa for magnesium alloys, compared to 15-25 GPa for human bone). This effectively reduces stress shielding effects, and they exhibit good biodegradability, eliminating the need for secondary surgery and reducing medical costs. Furthermore, magnesium is an essential trace element for the human body, requiring a certain daily intake. Due to these numerous advantages, magnesium is considered a promising biodegradable metallic material. Currently, many research institutions and universities have developed biodegradable magnesium alloy materials for medical applications, including vascular stents, bone plates, and bone screws.

[0003] Bone plates are perforated plate-shaped internal fixation devices for fractures. They are divided into two categories: ordinary bone plates and compression bone plates. Clinically, they are often used in conjunction with bone screws or bone wires.

[0004] The existing bone plates on the market have the following main defects: (1) Their function is relatively singular. Currently, bone plates are mainly used as fixation devices for fractures of the tibia and humerus; (2) Their biocompatibility is poor. During application, they are prone to causing subcutaneous edema, and during degradation, they generate toxic ions, all of which will cause damage to human tissues to the same extent; (3) They degrade too quickly, resulting in a short service life in the human body; (4) Ordinary bone plates have a simple molding method, and the subsequent machining is used to make the required rough outline as needed. Because the preparation method is too simple, Mismatch problems are likely to occur, resulting in reduced efficiency of the bone plate and lack of personalized application; (5) Traditional bone plates are mainly treated by micro-arc oxidation, electrodeposition and other methods. These methods have many disadvantages in the preparation of the film layer, such as: high energy consumption during production, difficulty in cooling the electrolyte, and troublesome subsequent processing, thin film layer, poor biocompatibility of the film, etc.; (6) Traditional bone plates cannot accurately prepare personalized biomaterials suitable for different patients according to their needs, and cannot accurately control the microstructure of the material.

[0005] The invention disclosed in CN202011222137.3 discloses a method for producing and molding anti-corrosion pipes, which adopts a conventional spraying method. This method has problems such as complicated procedures, a lot of manual work, low production efficiency, uneven anti-corrosion coating, poor anti-corrosion effect, a lot of material waste, and easy environmental pollution.

[0006] Therefore, it is necessary to study a method that is simple and quick to produce, low in energy consumption, and capable of producing multifunctional bone plates that are biocompatible, non-toxic, sterile, have controllable degradation rate, long service life, and are suitable for individualized patients, in order to solve the problems of high energy consumption, poor biocompatibility, single function, and excessively fast degradation rate of existing traditional bone plates. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a 3D-printed drug-eluting biodegradable magnesium alloy bone plate and its preparation method. By placing anti-inflammatory and analgesic drugs inside the magnesium alloy, its fixation function is not affected, while it is made more conducive to tissue recovery. 3D printing technology enables the rapid molding of the biodegradable magnesium alloy bone plate, and a new composite film layer is prepared on the alloy surface. This composite film layer not only significantly reduces the degradation rate of the magnesium alloy but also releases copper ions during the degradation process, thus playing a bactericidal role. The bone plate prepared by this invention has good biocompatibility, is non-toxic, bactericidal, has a controllable degradation rate, and a long service life. It can also be customized to meet the individualized medication needs of different patients.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A 3D-printed drug-eluting biodegradable magnesium alloy bone plate includes a biodegradable magnesium alloy substrate and a protective layer covering the surface of the substrate.

[0010] The substrate has a porous structure and can hold drugs inside;

[0011] The protective layer is a composite membrane layer; the composite membrane layer includes an antibacterial LDH membrane and a tannic acid membrane; this composite membrane layer can significantly reduce the degradation rate of magnesium alloy, extend the service life of the bone plate in the human body, and also play a bactericidal role. The LDH membrane is a layered double hydroxide (LDH) membrane.

[0012] Furthermore, the substrate is made of a high-strength biodegradable magnesium alloy system and is formed by 3D printing.

[0013] Preferably, the high-strength biodegradable magnesium alloy system is one of Mg-Ca, Mg-Zn, Mg-Al-Zn, Mg-Nd-Zn, or Mg-Zn-Ca systems.

[0014] Furthermore, the porous structure includes fixing holes, drug placement holes, and object placement holes; the fixing holes are through holes, distributed in the center or around the perimeter of the substrate, used for connecting and fixing the bone plate; the drug placement holes are central holes, arranged in an array, located on the upper and lower surfaces of the substrate, and the drug placement holes on the upper and lower surfaces do not overlap; the drug placement holes are used to hold drugs, and their depth is greater than half the thickness of the bone plate and less than three-quarters of the thickness of the bone plate; the object placement holes are through holes, used to place other materials or components that need to be placed inside the bone plate.

[0015] Preferably, the ratio of the number of drug placement holes to the surface area of ​​the bone plate is 1-3 drug placement holes per 50 square centimeters of bone plate; the larger the surface area of ​​the bone plate, the more drug placement holes there are, so as to facilitate the uniform filling and release of the drug.

[0016] Preferably, the surface area of ​​the bone plate is 500-1500 square centimeters; the number of drug placement holes is 10-50.

[0017] Preferably, the medicine placement hole is a circular hole with a depth of 0.1 mm-10 mm and a diameter of 2 mm-15 mm; the spacing is 1 cm-5 cm.

[0018] Preferably, the drug is encapsulated in a water-soluble film and then evenly placed in the holes of the drug placement hole, so that the drug is evenly distributed on the bone plate.

[0019] Preferably, the water-soluble film is a polyvinyl alcohol film.

[0020] Preferably, the thickness of the water-soluble film is 0.01 mm to 0.5 mm.

[0021] Preferably, the drug is a drug that promotes tissue healing.

[0022] Preferably, the fixing hole is circular or elongated elliptical. When it is elongated elliptical, the diameter in the length direction is 15mm-45mm and the diameter in the width direction is 5mm-15mm; when it is circular, the diameter is 4mm-15mm.

[0023] Preferably, the number of fixing holes is 1-5, evenly distributed in the middle or around the bone plate, to facilitate the connection and fixation of the bone plate.

[0024] Preferably, the placement hole is a circular hole, with 1-5 holes, evenly distributed in the middle and / or around the bone plate, and the hole diameter is 2 mm-15 mm.

[0025] Furthermore, the antibacterial LDH membrane is prepared using magnesium nitrate solution, aluminum nitrate solution, and copper nitrate solution; during the degradation of the bone plate, copper ions can be released from the membrane layer, which can play a bactericidal role.

[0026] Furthermore, the tannic acid membrane is prepared using a solution containing tannic acid.

[0027] Based on this, a further optimized technical solution is to install transient electronic devices inside the bone plate to facilitate monitoring of the physiological condition of the bone around the bone plate, thereby facilitating the patient's rehabilitation and maintenance.

[0028] The transient electronic device is made of a biodegradable material, primarily magnesium, which has good biocompatibility, degrades upon contact with water, leaves no residue in the body, and can accurately monitor the tissue condition at the injured site with a high degree of visualization.

[0029] Furthermore, there are 1-2 transient electronic devices, which are placed in the storage holes inside the bone plate.

[0030] Preferably, when there is one transient electronic device, it is placed in a placement hole near the center of the bone plate; when there are two transient electronic devices, they are placed in placement holes at both ends of the bone plate, in order to improve the accuracy of monitoring data and reduce errors caused by monitoring position.

[0031] Based on this, a further technical solution is a method for preparing a 3D-printed drug-loaded biodegradable magnesium alloy bone plate, which includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a magnesium alloy substrate and a porous structure, and the preparation of the external protective layer includes the preparation of an LDH film and a tannic acid film. The specific steps are as follows.

[0032] S1. Substrate Forming: A biodegradable magnesium alloy substrate and a porous model are modeled using 3D modeling software. The model is sliced ​​using Cura software, and the substrate and porous structure are printed using a 3D printer. The porous structure includes several fixing holes, several drug placement holes, and several object placement holes. The porous structure is formed by 3D printing. Before printing, the structural features such as the number, size, and arrangement of fixing holes, drug placement holes, and object placement holes are set using modeling software based on the given 3D drawing to establish a 3D substrate main model. Then, the substrate with fixing holes and drug placement holes and object placement holes on the upper and lower surfaces is printed.

[0033] S2. Placement of drugs and transient electronic devices: After the porous structure is formed, the drug is wrapped in a water-soluble film and placed in the drug placement hole; the transient electronic devices are placed in the object placement hole.

[0034] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate with drugs and transient electronic devices obtained in step S2 to seal the openings of the drug placement hole and the object placement hole, while keeping the fixing hole through, so as to realize the surface forming of the bone plate substrate and obtain the formed bone plate substrate (bare sample without film layer).

[0035] S4. Polishing treatment: Polish the bone plate substrate obtained in step S3 using mechanical and electrochemical polishing methods.

[0036] S5. Degreasing treatment: The polished bone plate substrate from step S4 is placed in a degreasing solution for degreasing treatment. The degreasing solution consists of sodium phosphate and sodium hydroxide solution. The degreasing temperature is 40℃-100℃ and the degreasing time is 2min-50min.

[0037] S6. Pickling and Alkali Washing: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment; the pickling solution is 5%-30% dilute nitric acid by volume, the pickling temperature is 10℃-40℃, and the pickling time is 0.5 min-3 min; the alkali washing solution is sodium hydroxide solution, the alkali washing temperature is 10℃-37℃, and the alkali washing time is 1 min-5 min.

[0038] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, and prepare the membrane according to n(Mg) 2+ ):n(Al 3 + Add aluminum nitrate solution to the flask in a ratio of (1-5):1, heat for 1-10 minutes, then add magnesium nitrate solution dropwise; heat for 2-15 minutes, then add copper nitrate solution dropwise. During each addition, ensure the mixed solution in the flask is alkaline and check the pH value. Stir vigorously at 20℃-100℃ for 1-10 hours, then adjust the pH value of the mixed solution again to make it alkaline, raise the temperature to 30℃-130℃, and react for 3-24 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0039] S8. Tannic acid membrane preparation: The bone plate sample covered with an antibacterial LDH membrane obtained in step S7 is placed in a tannic acid solution or a tannic acid membrane preparation conversion solution composed mainly of tannic acid and other reagents to obtain a bone plate sample covered with a composite membrane.

[0040] Furthermore, in step S1, the modeling software is any one of Pro / E, Solidworks, 3DMax, or UG.

[0041] Furthermore, in step S1, the drug placement holes are located on the upper and lower surfaces of the substrate and are arranged in an array, and the axes of the drug placement holes on the upper and lower surfaces do not coincide, and the drug placement holes do not overlap with each other.

[0042] Furthermore, in step S2, the size of the drug water-soluble film is smaller than the size of the drug placement holes opened on the upper and lower surfaces of the substrate, so as to facilitate its placement into the drug placement holes.

[0043] Furthermore, in step S2, the size of the transient electronic device is smaller than the size of the storage hole opened in the substrate, so that it can be easily placed into the storage hole.

[0044] Furthermore, in step S5, the concentration of sodium phosphate in the degreasing solution is 20 g / L-60 g / L; and the concentration of sodium hydroxide is 2 g / L-15 g / L.

[0045] Furthermore, in step S6, the concentration of the sodium hydroxide solution is 3 g / L-45 g / L.

[0046] Further, in step S7, the molar concentration of the magnesium nitrate solution is 0.05M-0.5M, the molar concentration of the aluminum nitrate solution is 0.01M-0.1M, and the molar concentration of the copper nitrate solution is 0.01M-0.25M; the pH value of the mixed solution is 7-9.5.

[0047] Furthermore, in step S7, the volume of the aluminum nitrate solution is 550 mL - 1500 mL.

[0048] Further, in step S8, the concentration of the tannic acid solution is 0.5 g / L-5.0 g / L; the other reagents are at least one of sodium borate, potassium fluoride, sodium phosphate, ammonium metavanadate, and potassium fluorozirconate, with concentrations of 0.3 g / L-1.5 g / L for sodium borate, 0.05 g / L-0.3 g / L for potassium fluoride, 0.2 g / L-1.0 g / L for sodium phosphate, 0.2 g / L-2.0 g / L for ammonium metavanadate, and 0.2 g / L-2.0 g / L for potassium fluorozirconate, respectively; the tannic acid membrane preparation conversion solution is prepared by adding water to tannic acid and other reagents, and the concentration of tannic acid in the tannic acid membrane preparation conversion solution is 2.5 g / L-5.0 g / L.

[0049] Because 3D printing technology can rapidly and accurately prepare personalized biomaterials suitable for different patients, it not only saves materials but also allows for precise control over the microstructure of the materials. Therefore, this invention can rapidly and accurately prepare personalized drug-eluting biodegradable magnesium alloy bone plates suitable for different patients. Beneficial effects

[0050] Compared with the prior art, the present invention has the following advantages.

[0051] 1. Traditional surface treatment methods focus on micro-arc oxidation and electrodeposition, which have many drawbacks in film preparation, such as high energy consumption during production, difficulty in cooling the electrolyte, cumbersome subsequent processing, thin films, and poor biocompatibility. This invention proposes a drug-eluting biodegradable magnesium alloy bone plate. The composite film on the surface of this bone plate effectively reduces the degradation rate and exhibits good adhesion to the substrate. Most importantly, the antibacterial LDH film releases copper ions during conversion, exerting a bactericidal effect and promoting wound healing. The tannic acid used to prepare the tannic acid film is an organic compound extracted from plants, which is non-toxic and biocompatible. The dual effects of the antibacterial LDH film and the tannic acid film result in a thick and dense composite film with excellent protective properties and good biocompatibility.

[0052] 2. Traditional bone plates are designed solely for fixation, offering a limited function. The drug-eluting biodegradable magnesium alloy bone plate proposed in this invention addresses this limitation. Furthermore, its design takes into account the intended service environment, allowing for the addition of releasable medications to facilitate patient recovery.

[0053] 3. The releasable drug of the present invention is placed inside the bone plate. In this way, the drug can be continuously released during the degradation process of the bone plate, promoting faster tissue recovery. Moreover, the drug placement hole is opened inside the bone plate, so it does not affect the mechanical properties in the early stage of degradation. As the degradation process continues, the drug is gradually and slowly released, avoiding the damage to the body caused by a large release at one time.

[0054] 4. The transient electronic devices used in this invention are biodegradable materials, mainly magnesium, which have good biocompatibility, can be degraded in water, leave no residue in the body, and can accurately monitor the tissue condition at the injured site with a high degree of visualization.

[0055] 5. The composite membrane and the drugs carried in the bone plate of this invention work synergistically on the injured tissue, reducing the intake of large amounts of antibiotics, anti-inflammatory drugs, analgesics and other drugs from outside the body, which is more conducive to tissue absorption and has a more significant effect. Attached Figure Description

[0056] Figure 1 This is a three-dimensional schematic diagram of the bone plate obtained in Embodiment 1 of the present invention.

[0057] Figure 2 This is a top view of the bone plate obtained in Embodiment 1 of the present invention.

[0058] Figure 3 This is a bottom view of the bone plate obtained in Embodiment 1 of the present invention.

[0059] Figure 4 This is a cross-sectional view of the bone plate obtained in Embodiment 1 of the present invention, parallel to the upper surface.

[0060] Figure 5 This is a macroscopic morphology diagram of the surface obtained in Embodiment 6 of the present invention.

[0061] Figure 6 This is a microscopic morphology diagram of the surface obtained in Example 6 of the present invention.

[0062] Figure 7 The polarization curve is obtained in Example 6 of the present invention.

[0063] Figure 8 This is the impedance spectrum obtained in Example 6 of the present invention.

[0064] Components, parts and numbers in the diagram: 1-bone plate; 2-fixation hole; 3-drug placement hole; 31-drug; 4-object placement hole; 41-transient electronic components. Implementation

[0065] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings, but the content of the present invention is not limited thereto.

[0066] like Figures 1-4 As shown, a 3D-printed drug-eluting biodegradable magnesium alloy bone plate 1 includes a biodegradable magnesium alloy substrate and a protective layer covering the surface of the substrate.

[0067] The substrate has a porous structure and can hold the drug 31 inside.

[0068] The protective layer is a composite membrane layer; the composite membrane layer includes an antibacterial LDH membrane and a tannic acid membrane; the composite membrane layer can significantly reduce the degradation rate of magnesium alloy, extend the service life of bone plate 1 in the human body, and also play a bactericidal role.

[0069] Furthermore, the substrate is made of a high-strength biodegradable magnesium alloy system and is formed by 3D printing, and its shape can be designed as needed.

[0070] Preferably, the high-strength biodegradable magnesium alloy system is one of Mg-Ca, Mg-Zn, Mg-Al-Zn, Mg-Nd-Zn, or Mg-Zn-Ca systems.

[0071] Furthermore, the porous structure includes fixing holes 2, drug placement holes 3, and object placement holes 4; the fixing holes 2 are through holes, distributed in the middle or around the perimeter of the substrate, used for connecting and fixing the bone plate 1; the drug placement holes 3 are central holes, arranged in an array, located on the upper and lower surfaces of the substrate, and the axes of the drug placement holes 3 on the upper and lower surfaces do not coincide, and the drug placement holes 3 do not overlap with each other; the drug placement holes 3 are used to hold the drug 31, and their depth is greater than half the thickness of the bone plate 1 and less than three-quarters of the thickness of the bone plate 1; the object placement holes 4 are through holes, used to place other materials or components that need to be placed inside the bone plate 1.

[0072] Preferably, the ratio of the number of drug placement holes 3 to the surface area of ​​the bone plate 1 is 1-3 drug placement holes 3 per 50 square centimeters of bone plate 1; the larger the surface area of ​​the bone plate 1, the more drug placement holes 3 there are, so as to facilitate the uniform filling and release of the drug 31.

[0073] Preferably, the surface area of ​​the bone plate 1 is 500-1500 square centimeters; the number of drug placement holes 3 is 10-50.

[0074] Preferably, the medicine placement hole 3 is a circular hole with a depth of 0.1mm-10mm and a diameter of 2mm-15mm; the spacing is 1cm-5cm.

[0075] Preferably, the drug 31 is wrapped in a water-soluble film and then evenly placed in the hole of the drug placement hole 3 so that the drug 31 is evenly distributed on the bone plate 1.

[0076] Preferably, the water-soluble film is a polyvinyl alcohol film.

[0077] Preferably, the thickness of the water-soluble film is 0.01 mm to 0.5 mm.

[0078] Preferably, the drug 31 is a drug 31 that promotes tissue healing.

[0079] Preferably, the fixing hole 2 is circular or elongated elliptical. When it is elongated elliptical, the diameter in the length direction is 15mm-45mm and the diameter in the width direction is 5mm-15mm; when it is circular, the diameter is 4mm-15mm.

[0080] Preferably, the number of fixing holes 2 is 1-5, evenly distributed in the middle and / or around the bone plate 1, so as to facilitate the connection and fixation of the bone plate 1.

[0081] Preferably, the placement hole 4 is a circular hole, with 1-5 holes, evenly distributed in the middle and / or around the bone plate 1, and the hole diameter is 2mm-15mm.

[0082] Furthermore, the antibacterial LDH membrane is prepared using magnesium nitrate solution, aluminum nitrate solution, and copper nitrate solution; during the degradation of the bone plate 1, copper ions can be released from the membrane layer, which can play a bactericidal role.

[0083] Furthermore, the tannic acid membrane is prepared using a solution containing tannic acid.

[0084] Based on this, a further optimized technical solution is to install a transient electronic device 41 inside the bone plate 1 to facilitate monitoring of the physiological condition of the bones around the bone plate 1, thereby facilitating the patient's rehabilitation and maintenance.

[0085] The transient electronic device 41 is made of a biodegradable material, mainly magnesium, which has good biocompatibility, degrades upon contact with water, leaves no residue in the body, and can accurately monitor the tissue condition at the injured site with a high degree of visualization.

[0086] Furthermore, there are 1-2 transient electronic devices 41, which are placed in the storage holes 4 inside the bone plate 1.

[0087] Preferably, when there is one transient electronic device 41, it is placed in the placement hole 4 near the center of the bone plate 1; when there are two transient electronic devices 41, they are placed in the placement holes 4 located at both ends of the bone plate 1, so as to improve the accuracy of monitoring data and reduce errors caused by monitoring position.

[0088] Example 1

[0089] The preparation of a 3D-printed drug-loaded biodegradable Mg-Ca alloy bone plate 1 includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a Mg-Ca alloy substrate and a porous structure, and the preparation of the external protective layer includes the preparation of an LDH film and a tannic acid film. The specific steps are as follows.

[0090] S1. Substrate Forming: The Mg-Ca alloy substrate and porous model were modeled using 3DMAX software (the surface area of ​​bone plate 1 is 620 square centimeters; the diameter of medicine placement hole 3 is 3 mm, and the number is 18, of which 9 are opened on the upper surface and 9 are opened on the lower surface; the diameter of object placement hole 4 is 2 mm, and the number is 3; the fixing hole 2 is a circular hole with a diameter of 6 mm, and the number is 4); the model was sliced ​​using Cura software, and the printing process was completed using a 3D printer.

[0091] S2. Placement of drug 31 and transient electronic device 41: Place one transient electronic device 41 into the placement hole 4 in the middle of the substrate, wrap the anti-inflammatory drug with a water-soluble film with a thickness of 0.01mm, and then insert it into the drug placement holes 3 on the upper and lower surfaces of the substrate to make the drug 31 evenly distributed.

[0092] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate on which the drug 31 and transient electronic device 41 were placed in step S2, to seal the openings of the drug placement hole 3 and the object placement hole 4, while keeping the fixing hole 2 open, so as to realize the surface forming of the biodegradable Mg-Ca alloy bone plate substrate, and obtain the formed bone plate substrate (bare sample without film layer).

[0093] S4. Polishing treatment: The Mg-Ca alloy bone plate substrate obtained in step S3 is polished using mechanical and electrochemical polishing methods to obtain a clean surface.

[0094] S5. Degreasing treatment: Place the polished bone plate substrate from step S4 into a degreasing solution and immerse it at 40°C for 30 minutes to perform degreasing treatment. The degreasing solution consists of 30 g / L sodium phosphate and 5 g / L sodium hydroxide.

[0095] S6. Pickling and Alkali Washing Treatment: The degreased Mg-Ca alloy mortise and tenon plate substrate from step S5 is subjected to pickling and alkali washing treatment. First, the degreased Mg-Ca alloy mortise and tenon plate substrate is immersed in a pickling solution at 15°C for 1 minute. The pickling solution consists of 20% dilute nitric acid (volume percentage) to remove surface oxides. After pickling, the surface is rinsed with deionized water and then placed in an alkali washing solution at 15°C for 5 minutes. The alkali washing solution consists of 4g / L sodium hydroxide. After alkali washing, the surface is rinsed with deionized water and then dried with warm air until the surface is dry and free of water stains.

[0096] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, add 1500 mL of aluminum nitrate solution (concentration 0.06 M) to the flask, heat for 2 min, and then add magnesium nitrate solution (concentration 0.04 M) dropwise to make n(Mg 2+ ):n(Al 3+ The ratio of copper nitrate to copper nitrate was 1:1. After heating for 2 minutes, copper nitrate solution (concentration of 0.08 M) was added dropwise. During each dropwise addition, the mixed solution was kept alkaline and the pH value was kept between 7 and 9.5. The mixture was stirred vigorously at 40°C for 2 hours. The pH value of the mixed solution was adjusted again to make it alkaline. The temperature was raised to 50°C and the reaction was carried out for 5 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0097] S8. Preparation of tannic acid membrane: The bone plate sample covered with the antibacterial LDH membrane obtained in step S7 was placed in a 1 g / L tannic acid solution and reacted at 20°C for 10 min to obtain the tannic acid membrane layer. Thus, the bone plate 1 sample was obtained with a composite membrane layer composed of LDH membrane layer and tannic acid membrane layer as a protective layer.

[0098] The bone plate 1 prepared by the above process is covered with a dense composite film on its surface. The film is relatively thick, has good biocompatibility, and takes more than 3 months to degrade in the human body.

[0099] The three-dimensional schematic diagram, top view, bottom view and cross-sectional view of the bone plate 1 obtained from Example 1 are shown below. Figure 1 , Figure 2 , Figure 3 and Figure 4 As shown.

[0100] Example 2

[0101] The preparation of a 3D-printed drug-loaded biodegradable Mg-Zn-Ca alloy bone plate 1 includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a Mg-Zn-Ca alloy substrate and a porous structure. The preparation of the external protective layer includes the preparation of an LDH membrane and a tannic acid membrane. The specific steps are as follows.

[0102] S1. Substrate Forming: The Mg-Zn-Ca alloy substrate and porous model were modeled using Pro / Engineer software (the surface area of ​​bone plate 1 is 710 square centimeters; the diameter of medicine placement hole 3 is 5 mm and the number is 20; the diameter of object placement hole 4 is 5 mm and the number is 2; the fixing hole 2 is a circular hole with a diameter of 6 mm and the number is 2); the model was sliced ​​using Simplify3D software, and the printing process was completed using a 3D printer.

[0103] S2. Placement of drug 31 and transient electronic device 41: Place one transient electronic device 41 into the placement hole 4 in the middle of the substrate, wrap the anti-inflammatory drug with a water-soluble film with a thickness of 0.03 mm, and then insert it into the drug placement hole 3 to make the drug 31 evenly distributed.

[0104] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate obtained in step S2, on which the drug 31 and transient electronic device 41 are placed, to seal the openings of the drug placement hole 3 and the object placement hole 4, while keeping the fixing hole 2 open, so as to realize the surface forming of the biodegradable Mg-Zn-Ca alloy bone plate substrate, and obtain the formed bone plate substrate (bare sample without film layer).

[0105] S4. Polishing treatment: The Mg-Zn-Ca alloy bone plate substrate obtained in step S3 is polished using mechanical and electrochemical polishing methods to obtain a clean surface.

[0106] S5. Degreasing treatment: Place the polished bone plate substrate from step S4 into a degreasing solution and immerse it at 40°C for 30 minutes to perform degreasing treatment. The degreasing solution consists of 35 g / L sodium phosphate and 5 g / L sodium hydroxide.

[0107] S6. Pickling and Alkali Washing Treatment: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment. First, the degreased Mg-Zn-Ca alloy bone plate substrate is immersed in a pickling solution for 0.5 min at a pickling temperature of 25°C. The pickling solution consists of 25% dilute nitric acid (volume percentage) to remove surface oxides. After pickling, the surface is rinsed with deionized water and then placed in an alkali washing solution at a temperature of 20°C for 4 min. The alkali washing solution consists of 5 g / L sodium hydroxide. After alkali washing, the surface is rinsed with deionized water and then dried with warm air until the surface is dry and free of water stains.

[0108] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, add 1000 mL of aluminum nitrate solution (concentration 0.08 M) to the flask, heat for 4 min, and then add magnesium nitrate solution (concentration 0.16 M) dropwise to make n(Mg 2+ ):n(Al 3+ The ratio of copper nitrate to copper nitrate was 2:1. After heating for 4 minutes, copper nitrate solution (concentration of 0.15 M) was added dropwise. During each dropwise addition, the mixed solution was kept alkaline and the pH value was kept between 7 and 9.5. The mixture was stirred vigorously at 50°C for 2 hours. The pH value of the mixed solution was adjusted again to make it alkaline. The temperature was raised to 60°C and the reaction was carried out for 4 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0109] S8. Preparation of tannic acid membrane: The bone plate sample covered with the antibacterial LDH membrane obtained in step S7 was placed in a 2 g / L tannic acid solution and reacted at 20°C for 10 min to obtain the tannic acid membrane layer. Thus, the bone plate sample 1 was obtained with a composite membrane layer composed of LDH membrane layer and tannic acid membrane layer as a protective layer.

[0110] Example 3

[0111] The preparation of a 3D-printed drug-loaded biodegradable Mg-Zn-Ca-Nd alloy bone plate 1 includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a Mg-Zn-Ca-Nd alloy substrate and a porous structure. The preparation of the external protective layer includes the preparation of an LDH film and a tannic acid film. The specific steps are as follows.

[0112] S1. Substrate Forming: The Mg-Zn-Ca-Nd alloy substrate and porous model were modeled using SolidWorks software (the surface area of ​​bone plate 1 is 860 square centimeters; the diameter of medicine placement hole 3 is 6 mm and the number is 25; the diameter of object placement hole 4 is 8 mm and the number is 2; the fixing hole 2 is a circular hole with a diameter of 9 mm and the number is 2); the model was sliced ​​using Hori3D software and the printing process was completed using a 3D printer.

[0113] S2. Placement of drug 31 and transient electronic device 41: Place one transient electronic device 41 into the placement hole 4 in the middle of the substrate, wrap the anti-inflammatory drug with a water-soluble film with a thickness of 0.02 mm, and then insert it into the drug placement hole 3 to make the drug 31 evenly distributed.

[0114] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate on which the drug 31 and transient electronic device 41 were placed in step S2, to seal the openings of the drug placement hole 3 and the object placement hole 4, while keeping the fixing hole 2 open, so as to realize the surface forming of the biodegradable Mg-Zn-Ca-Nd alloy bone plate substrate, and obtain the formed bone plate substrate (bare sample without film layer).

[0115] S4. Polishing treatment: The Mg-Zn-Ca-Nd alloy bone plate substrate obtained in step S3 is polished using mechanical and electrochemical polishing methods to obtain a clean surface.

[0116] S5. Degreasing treatment: Place the polished bone plate substrate from step S4 into a degreasing solution and immerse it at 50°C for 20 minutes to perform degreasing treatment. The degreasing solution consists of 40 g / L sodium phosphate and 5 g / L sodium hydroxide.

[0117] S6. Pickling and Alkali Washing Treatment: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment. First, the degreased Mg-Zn-Ca-Nd alloy bone plate substrate is immersed in a pickling solution for 0.5 min at a pickling temperature of 20°C. The pickling solution contains 30% dilute nitric acid (volume percentage) to remove surface oxides. After pickling, the surface is rinsed with deionized water and then placed in an alkali washing solution at a temperature of 22°C for 3 min. The alkali washing solution contains 6 g / L sodium hydroxide. After alkali washing, the surface is rinsed with deionized water and then dried with warm air until the surface is dry and free of water stains.

[0118] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, add 1200 mL of aluminum nitrate solution (concentration 0.1 M) to the flask, heat for 5 min, and then add magnesium nitrate solution (concentration 0.3 M) dropwise to make n(Mg 2+ ):n(Al 3+ The ratio of copper nitrate to copper nitrate was 3:1. After heating for 5 minutes, copper nitrate solution (concentration of 0.20 M) was added dropwise. During each dropwise addition, the mixed solution was kept alkaline and the pH value was kept between 7 and 9.5. The mixture was stirred vigorously at 60°C for 2 hours. The pH value of the mixed solution was adjusted again, the temperature was raised to 70°C, and the reaction was carried out for 4 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0119] S8. Preparation of tannic acid membrane: The bone plate sample covered with the antibacterial LDH membrane obtained in step S7 was placed in a 4 g / L tannic acid solution and reacted at 20°C for 5 min to obtain the tannic acid membrane layer. Thus, the bone plate 1 sample was obtained with a composite membrane layer composed of LDH membrane layer and tannic acid membrane layer as a protective layer.

[0120] Example 4

[0121] The preparation of a 3D-printed drug-loaded biodegradable Mg-Zn-Nd-Zr alloy bone plate 1 includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a Mg-Zn-Nd-Zr alloy substrate and a porous structure. The preparation of the external protective layer includes the preparation of an LDH membrane and a tannic acid membrane. The specific steps are as follows.

[0122] S1. Substrate Forming: The Mg-Zn-Nd-Zr alloy substrate and porous model were modeled using Maya software (the surface area of ​​the bone plate is 1200 square centimeters; the diameter of the medicine placement hole 3 is 6 mm and the number is 30; the diameter of the object placement hole 4 is 12 mm and the number is 3; the fixing hole 2 is a circular hole with a diameter of 10 mm and the number is 2); the model was sliced ​​using Slic3r software and the printing process was completed using a 3D printer.

[0123] S2. Placement of drug 31 and transient electronic device 41: Place one transient electronic device 41 into the placement hole 4 in the middle of the substrate, wrap the anti-inflammatory drug with a water-soluble film with a thickness of 0.03 mm, and then insert it into the drug placement hole 3 to make the drug 31 evenly distributed.

[0124] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate on which the drug 31 and transient electronic device 41 were placed in step S2, to seal the openings of the drug placement hole 3 and the object placement hole 4, while keeping the fixing hole 2 open, so as to realize the surface forming of the biodegradable Mg-Zn-Nd-Zr alloy bone plate substrate, and obtain the formed bone plate substrate (bare sample without film layer).

[0125] S4. Polishing treatment: The Mg-Zn-Nd-Zr alloy bone plate substrate obtained in step S3 is polished using mechanical and electrochemical polishing methods to obtain a clean surface.

[0126] S5. Degreasing treatment: Place the polished bone plate substrate from step S4 into a degreasing solution and immerse it at 50°C for 15 minutes to perform degreasing treatment. The degreasing solution consists of 45 g / L sodium phosphate and 5 g / L sodium hydroxide.

[0127] S6. Pickling and Alkali Washing Treatment: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment. First, the degreased Mg-Zn-Nd-Zr alloy bone plate substrate is immersed in a pickling solution for 1.5 min at a pickling temperature of 30°C. The pickling solution consists of 10% dilute nitric acid (volume percentage) to remove surface oxides. After pickling, the surface is rinsed with deionized water and then placed in an alkali washing solution at a temperature of 25°C for 3 min. The alkali washing solution consists of 5 g / L sodium hydroxide. After alkali washing, the surface is rinsed with deionized water and then dried with warm air until the surface is dry and free of water stains.

[0128] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, add 1000 mL of aluminum nitrate solution (concentration 0.08 M) to the flask, heat for 5 min, and then add magnesium nitrate solution (concentration 0.4 M) dropwise to make n(Mg 2+ ):n(Al 3+ The ratio of copper nitrate to copper nitrate was 4:1. After heating for 5 minutes, copper nitrate solution (concentration of 0.25 M) was added dropwise. During each dropwise addition, the mixed solution was kept alkaline and the pH value was kept between 7 and 9.5. The mixture was stirred vigorously at 60°C for 2 hours. The pH value of the mixed solution was adjusted again to make it alkaline. The temperature was raised to 80°C and the reaction was carried out for 3 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0129] S8. Preparation of tannic acid membrane: The bone plate sample covered with the antibacterial LDH membrane obtained in step S7 was placed in a conversion solution mainly composed of tannic acid. The conversion solution consisted of 4.0 g / L tannic acid, 1.0 g / L ammonium metavanadate, and 0.8 g / L potassium fluorozirconate. The reaction was carried out at 30°C for 5 min to obtain the tannic acid membrane layer. Thus, the bone plate sample 1 was obtained with a composite membrane layer composed of LDH membrane layer and tannic acid membrane layer as a protective layer.

[0130] Example 5

[0131] The preparation of a 3D-printed drug-loaded biodegradable Mg-Ca-Nd alloy bone plate 1 includes the molding of an internal drug-loaded substrate and the preparation of an external protective layer. The substrate molding includes the molding of a Mg-Ca-Nd alloy substrate and a porous structure. The preparation of the external protective layer includes the preparation of an LDH membrane and a tannic acid membrane. The specific steps are as follows.

[0132] S1. Substrate Forming: The Mg-Ca-Nd alloy substrate and porous model were modeled using UG software (the surface area of ​​bone plate 1 is 1320 square centimeters; the diameter of medicine placement hole 3 is 6 mm and the number is 30; the diameter of object placement hole 4 is 15 mm and the number is 4; the fixing hole 2 is a circular hole with a diameter of 12 mm and the number is 4); the model was sliced ​​using XBuilder software and the printing process was completed using a 3D printer.

[0133] S2. Placement of drug 31 and transient electronic device 41: Place one transient electronic device 41 into the placement hole 4 in the middle of the substrate, wrap the anti-inflammatory drug with a water-soluble film with a thickness of 0.02 mm, and then insert it into the drug placement hole 3 to make the drug 31 evenly distributed.

[0134] S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate obtained in step S2, on which the drug 31 and transient electronic device 41 are placed, to seal the openings of the drug placement hole 3 and the object placement hole 4, while keeping the fixing hole 2 open, so as to realize the surface forming of the biodegradable Mg-Ca-Nd alloy bone plate substrate, and obtain the formed bone plate substrate (bare sample without film layer).

[0135] S4. Polishing treatment: The Mg-Ca-Nd alloy bone plate substrate obtained in step S3 is polished using mechanical and electrochemical polishing methods to obtain a clean surface.

[0136] S5. Degreasing treatment: Place the polished bone plate substrate from step S4 into a degreasing solution and immerse it at 55°C for 10 minutes to perform degreasing treatment. The degreasing solution consists of 50 g / L sodium phosphate and 5 g / L sodium hydroxide.

[0137] S6. Pickling and Alkali Washing Treatment: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment. First, the degreased Mg-Ca-Nd alloy bone plate substrate is immersed in a pickling solution at 30°C for 1.5 min to remove surface oxides. After pickling, the surface is rinsed with deionized water and then placed in an alkali washing solution at 30°C for 2.5 min. The alkali washing solution contains 6 g / L sodium hydroxide. After alkali washing, the surface is rinsed with deionized water and then dried with warm air until the surface is dry and free of water stains.

[0138] S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, add 1000 mL of aluminum nitrate solution (concentration 0.05 M) to the flask, heat for 7 min, and then add magnesium nitrate solution (concentration 0.25 M) dropwise to make n(Mg 2+ ):n(Al 3+The ratio of copper nitrate to copper nitrate was 5:1. After heating for 7 minutes, copper nitrate solution (concentration of 0.20 M) was added dropwise. During each dropwise addition, the mixed solution was kept alkaline and the pH value was kept between 7 and 9.5. The mixture was stirred vigorously at 60°C for 2 hours. The pH value of the mixed solution was adjusted again to make it alkaline. The temperature was raised to 100°C and the reaction was carried out for 2 hours to obtain a bone plate sample covered with an antibacterial LDH membrane.

[0139] S8. Preparation of tannic acid membrane: The bone plate sample covered with the antibacterial LDH membrane obtained in step S7 was placed in a conversion solution mainly composed of tannic acid. The composition of the conversion solution was 3.0 g / L tannic acid, 1.0 g / L ammonium metavanadate, and 1.5 g / L potassium fluorozirconate. The reaction was carried out at 30°C for 5 min to obtain the tannic acid membrane layer. Thus, the bone plate sample 1 was obtained with a composite membrane layer composed of LDH membrane layer and tannic acid membrane layer as a protective layer.

[0140] Example 6

[0141] The Mg-Ca alloy bone plate substrate (bare sample without film), the bone plate sample covered with antibacterial LDH film, and the bone plate sample covered with composite film obtained in Example 1 were immersed in simulated body fluid for 5 days. The surface macromorphology was observed, and the surface macromorphology image is shown below. Figure 5 As shown. By Figure 5 It can be seen that after soaking for five days, compared with LDH membrane and composite membrane samples, the bare sample surface showed more white substance (originating from Mg). 2+ +H 2 O→Mg(OH)2). The samples covered with LDH film and those covered with composite film showed inhibited corrosion due to the protection of the surface film, with the composite film exhibiting better protective properties.

[0142] The Mg-Ca alloy bone plate substrate (bare sample without film), the bone plate sample covered with antibacterial LDH film, and the bone plate sample covered with composite film obtained in Example 1 were immersed in simulated body fluid for 5 days. The surface micromorphology was observed, and the surface micromorphology images are shown below. Figure 6 As shown. After soaking for five days, by Figure 6 It can be seen that for the bare sample, when there is no film on the Mg-Ca surface, the corrosion rate is fast, a large number of corrosion products appear, and the degradation is severe; the sample covered with an LDH film only has an LDH film layer, and cracks appear on the film surface, and relatively dense, fine corrosion products appear on the film surface; the sample covered with a composite film layer has a relatively dense film surface, fewer cracks appear, a small number of corrosion products are scattered on the surface, the degradation rate is slow, and the film layer plays the best protective role.

[0143] Polarization curves and impedance spectra were plotted to compare and analyze the corrosion behavior of the Mg-Ca alloy bone plate substrate (bare sample without film), the bone plate sample covered with an antibacterial LDH film, and the bone plate sample covered with a composite film obtained in Example 1. The polarization resistance of the three samples showed that the composite film sample had the highest polarization resistance, followed by the LDH film sample, and the bare sample had the lowest, indicating that the composite film sample had the best corrosion resistance. A smaller slope in the polarization curve indicated easier corrosion, showing that the composite film sample had the best corrosion resistance. This is consistent with the corrosion behavior observed in the impedance spectra. The polarization curves are shown below. Figure 7 As shown, the impedance spectrum is as follows Figure 8 As shown.

[0144] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the invention. Any technical solution implemented within the scope of the claims of this application, or any possible variations and modifications made by those skilled in the art using the methods disclosed above, shall fall within the protection scope of the present invention.

Claims

1. A 3D-printed drug-eluting biodegradable magnesium alloy bone plate, characterized in that: The device includes a biodegradable magnesium alloy substrate and a protective layer covering the substrate surface. The substrate has a porous structure and carries medication internally. The protective layer is a composite film layer, comprising an antibacterial LDH film and a tannic acid film. The porous structure includes fixing holes, drug placement holes, and object placement holes. The fixing holes are through holes, distributed in the center or around the perimeter of the substrate, used for connecting and fixing the bone plate. The drug placement holes are central holes, arranged in an array, located on the upper and lower surfaces of the substrate, with the drug placement holes on the upper and lower surfaces not overlapping. The drug placement holes are used to carry medication. The object placement holes are used to place other materials or components that need to be placed inside the bone plate. The substrate is made of a high-strength biodegradable magnesium alloy system and is formed by 3D printing. The high-strength biodegradable magnesium alloy system is one of Mg-Ca, Mg-Zn, Mg-Al-Zn, Mg-Nd-Zn or Mg-Zn-Ca systems; The ratio of the number of drug placement holes to the surface area of ​​the bone plate is 1-3 drug placement holes per 50 square centimeters of bone plate. The drug is encapsulated in a water-soluble film and then evenly placed in the holes of the drug placement hole, so that the drug is evenly distributed on the bone plate. The water-soluble film is a polyvinyl alcohol film; the thickness of the water-soluble film is 0.01 mm-0.5 mm; The tannic acid membrane is prepared using a solution containing tannic acid; the antibacterial LDH membrane is prepared using magnesium nitrate solution, aluminum nitrate solution, and copper nitrate solution. Transient electronic devices are installed in the placement hole to monitor the physiological condition of the bone around the bone plate.

2. The preparation method of the 3D-printed drug-eluting biodegradable magnesium alloy bone plate as described in claim 1 shall be carried out according to the following steps: S1. Substrate Forming: A biodegradable magnesium alloy substrate and a porous model are modeled using 3D modeling software. The model is sliced ​​using the software, and the substrate and porous structure are printed using a 3D printer. The porous structure includes several fixing holes, several drug placement holes, and several object placement holes. The porous structure is formed by printing the entire structure together using 3D printing. S2. Placement of drugs and transient electronic devices: After the porous structure is formed, the drug is wrapped in a water-soluble film and placed in the drug placement hole; the transient electronic devices are placed in the storage hole. S3. Substrate surface forming: Repeat step S1, and print a layer of magnesium alloy on the surface of the bone plate substrate on which the drug and transient electronic device are placed, obtained in step S2, to seal the openings of the drug placement hole and the object placement hole, while keeping the fixing hole through, so as to achieve the substrate surface forming of the bone plate. S4. Polishing treatment: Polish the bone plate substrate obtained in step S3 using mechanical and electrochemical polishing methods; S5. Degreasing treatment: The polished bone plate substrate in step S4 is placed in a degreasing solution for degreasing treatment. The degreasing solution is composed of sodium phosphate and sodium hydroxide solution. The degreasing temperature is 40℃-100℃ and the degreasing time is 2min-50min. S6. Pickling and Alkali Washing: The degreased bone plate substrate from step S5 is subjected to pickling and alkali washing treatment; the pickling solution is 5%-30% dilute nitric acid by volume, the pickling temperature is 10℃-40℃, and the pickling time is 0.5min-3min; the alkali washing solution is sodium hydroxide solution, the alkali washing temperature is 10℃-37℃, and the alkali washing time is 1min-5min. S7. LDH membrane preparation: Place the bone plate substrate washed with alkali in step S6 into a flask, and prepare the membrane according to n(Mg) 2+ ) :n(Al 3+ Add aluminum nitrate solution to a flask with a ratio of (1-5):1, heat for 1-10 minutes, then add magnesium nitrate solution dropwise; heat for 2-15 minutes, then add copper nitrate solution dropwise. During each addition, ensure the mixed solution in the flask is alkaline and check the pH value. Stir vigorously at 20℃-100℃ for 1-10 hours, then adjust the pH value of the mixed solution again to make it alkaline, raise the temperature to 30℃-130℃, and react for 3-24 hours to obtain a bone plate sample covered with an antibacterial LDH membrane. S8. Tannic acid membrane preparation: The bone plate sample covered with an antibacterial LDH membrane obtained in step S7 is placed in a tannic acid solution or a tannic acid membrane preparation conversion solution composed mainly of tannic acid and other reagents to obtain a bone plate sample covered with a composite membrane. In step S1, the modeling software is any one of Pro / E, Solidworks, 3DMax or UG; the drug placement holes are located on the upper and lower surfaces of the substrate, arranged in an array, and the drug placement holes on the upper and lower surfaces do not overlap; The model slicing software can be any one of Cura, Simplify3D, Hori3D Software, Slic3r, or XBuilder; In step S2, the size of the drug water-soluble film is smaller than the size of the drug placement holes opened on the upper and lower surfaces of the substrate, so as to facilitate its placement into the drug placement holes; the size of the transient electronic device is smaller than the size of the object placement hole opened on the substrate, so as to facilitate its placement into the object placement hole. In step S5, the concentration of sodium phosphate in the degreasing solution is 20 g / L-60 g / L; the concentration of sodium hydroxide is 2 g / L-15 g / L. In step S6, the concentration of the sodium hydroxide solution is 3 g / L-45 g / L; In step S7, the molar concentration of the magnesium nitrate solution is 0.05M-0.5M by mass, the molar concentration of the aluminum nitrate solution is 0.01M-0.1M, and the molar concentration of the copper nitrate solution is 0.01M-0.25M; the pH value of the mixed solution is 7-9.

5. In step S7, the volume of the aluminum nitrate solution is 550 mL - 1500 mL; In step S8, the concentration of the tannic acid solution is 0.5 g / L-5.0 g / L; the other reagents are at least one of sodium borate, potassium fluoride, sodium phosphate, ammonium metavanadate, and potassium fluorozirconate, with concentrations of 0.3 g / L-1.5 g / L for sodium borate, 0.05 g / L-0.3 g / L for potassium fluoride, 0.2 g / L-1.0 g / L for sodium phosphate, 0.2 g / L-2.0 g / L for ammonium metavanadate, and 0.2 g / L-2.0 g / L for potassium fluorozirconate, respectively; the tannic acid membrane preparation conversion solution is prepared by adding water to tannic acid and other reagents, and the concentration of tannic acid in the tannic acid membrane preparation conversion solution is 2.5 g / L-5.0 g / L.

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