A bone implant prosthesis, its preparation method and administration method

Abstract

This application discloses a bone implant prosthesis, relating to the field of orthopedic implant technology, aiming to solve the problems of uncontrollable drug release, poor targeting, and safety hazards. The prosthesis includes a bone implant matrix and magnetic particles. The magnetic particles are doped into a designated area of ​​the matrix at a low mass percentage of 0.5%-5%, forming a chain-like structure within this area to generate a magnetic field gradient for capturing magnetized drugs, while ensuring the overall magnetic field strength of the prosthesis does not exceed 5 mT. This structure can generate a highly efficient local magnetic field gradient under extremely low overall magnetic field conditions, thereby accurately capturing intravenously injected magnetized drugs and achieving efficient drug accumulation in the lesion area. This invention has the advantages of precise targeting, high safety, compatibility with MRI examination, and flexible and controllable drug delivery protocols.

Description

Technical Field

[0001] This application relates to the field of medical device technology, specifically to a bone implant prosthesis, its preparation method, and its administration method. Background Technology

[0002] Bone implants are indispensable medical devices in orthopedic repair and reconstruction surgery, and are widely used in clinical settings such as bone defect filling, spinal fusion, and joint replacement. Polymer materials such as polyetheretherketone (PEEK), polyaryletherketone (PAEK), and polyamide (PA) have become commonly used matrix materials for bone implants due to their excellent biocompatibility, mechanical properties, and radiopermeability.

[0003] In bone implantation therapy, medication is often used in conjunction to promote osteogenesis, prevent infection, or inhibit tumor recurrence. Traditional drug delivery methods mainly include systemic administration (such as intravenous injection) and local drug delivery. While systemic administration is simple to perform, the drug is distributed throughout the body via the bloodstream, with only a small amount reaching the area around the implant, resulting in poor targeting, low therapeutic efficiency, and a high risk of systemic adverse reactions. Local drug delivery technology typically loads the drug directly onto the surface or interior of the implant material. Although it achieves local treatment, it suffers from drawbacks such as poor drug-material compatibility, uncontrollable release rates (e.g., initial burst release, insufficient release later), and a fixed delivery method that cannot be adjusted according to the patient's condition, making clinical translation difficult.

[0004] Therefore, developing a bone implant material and its corresponding treatment method that can achieve precise drug targeting and controllable drug release rate is of great clinical significance and application value. Summary of the Invention

[0005] The first aspect of this application provides a bone implant prosthesis, comprising: Bone implant prosthesis matrix; And multiple biocompatible magnetic particles, which are doped or coated on a designated area of ​​the bone implant prosthesis matrix and form a chain structure within the designated area to generate a magnetic field gradient for capturing magnetized drugs; the axis of the chain structure is consistent with the direction of the magnetic moment vector of the magnetic particles. The mass of the magnetic particles is 0.5%-5% of the total mass of the bone implant prosthesis, and the overall magnetic field strength of the bone implant prosthesis is ≤5mT.

[0006] Furthermore, the designated area is the two ends of the bone implant prosthesis base.

[0007] Furthermore, the density of the magnetic particles decreases gradually from both ends of the bone implant prosthesis matrix towards the middle of the bone implant prosthesis matrix.

[0008] Furthermore, the magnetic particles include soft magnetic particles and hard magnetic particles. The hard magnetic particles are used to provide a magnetic field gradient after magnetization; the soft magnetic particles are used to assist in constructing chain-like structures; the molar ratio of soft magnetic particles to hard magnetic particles is 1:9-1:11.

[0009] A second aspect of this application provides a method for preparing a bone implant prosthesis as described in the first aspect of this application, comprising the following steps: The raw materials are mixed and granulated to obtain the molding material; the raw materials include matrix materials and magnetic particles used to form the matrix of bone implant prosthesis. The molding material is fed into the 3D printing nozzle; The molding material is heated to a molten state through a 3D printing nozzle and extruded from the nozzle of the 3D printing nozzle; during the process of the molten molding material flowing in the 3D printing nozzle, a directional magnetic field is applied to the molding material to induce the magnetic particles in the molding material to assemble into a chain structure; by controlling the extrusion speed of the molding material and the relative moving speed of the 3D printing nozzle, the extruded molten material is deposited along a preset path to form a bone implant prosthesis embryo with the desired shape. The bone implant embryo is solidified and shaped to form a bone implant prosthesis.

[0010] Furthermore, the direction of the directional magnetic field is consistent with the direction of the molten molding material flowing in the 3D printing nozzle.

[0011] Furthermore, the directional magnetic field includes a pulsed magnetic field and a constant magnetic field. The pulsed magnetic field is used to induce the magnetic domains of the magnetic particles to generate an initial orientation; the constant magnetic field is used to drive the magnetic particles to complete spatial displacement and assemble into a chain-like structure.

[0012] Furthermore, during the flow of the molten molding material in the 3D printing nozzle, a directional magnetic field is applied to the molding material, including: At the first node in the flow path of the molding material, a pulsed magnetic field is applied to the molding material, and at the second node in the flow path of the molding material, a constant magnetic field is applied to the molding material; the molding material first flows through the first node and then through the second node.

[0013] Furthermore, the magnetic particles include soft magnetic particles and hard magnetic particles, with a molar ratio of soft magnetic particles to hard magnetic particles of 1:9 to 1:11. The interval between the first node and the second node is determined by the ratio of soft magnetic particles to hard magnetic particles. The higher the proportion of soft magnetic particles, the shorter the interval between the first node and the second node.

[0014] Furthermore, there are at least two molding materials, and the magnetic particles in the at least two molding materials have different densities; Feeding molding materials into a 3D printing nozzle includes: controlling the feed rate when at least two molding materials are fed into a 3D printing nozzle; By controlling the extrusion speed of the molding material and the relative movement speed of the 3D printing nozzle, magnetic particles are incorporated into a designated area of ​​the bone implant prosthesis matrix. This includes controlling the feeding speed of at least two molding materials when they are fed into the 3D printing nozzle, the extrusion speed of the molding material, and the relative movement speed of the 3D printing nozzle, so that magnetic particles are incorporated into a designated area of ​​the bone implant prosthesis matrix at a desired density.

[0015] A third aspect of this application provides a method for administering medication, the method comprising the following steps: The bone implant prosthesis of the first aspect of this application or the bone implant prosthesis prepared according to the preparation method of the second aspect of this application is implanted into the patient's body; Magnetized drugs are injected intravenously into the patient's body to capture the magnetic drugs circulating through the bone implant prosthesis under the drive of blood circulation by utilizing the magnetic field gradient generated by the magnetic particles in the bone implant prosthesis. Among them, the magnetized drug is a drug with a magnetic marker that is combined through physical adsorption or chemical coupling; the axial direction of the chain structure is parallel to the blood flow direction when the magnetized drug flows through the bone implant prosthesis.

[0016] Furthermore, it also includes applying an external magnetic field to the area outside the patient corresponding to the bone implant prosthesis to enhance the capture efficiency of magnetized drugs. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the bone implant prosthesis provided in the embodiments of this application.

[0018] Figure 2 This is a schematic diagram of the 3D printing apparatus used in the embodiments of this application. Detailed Implementation

[0019] The preferred embodiments of the present invention will be described below with reference to the accompanying drawings. It should be understood that the preferred embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0020] Before providing a further detailed description of the embodiments of this application, some of the nouns and terms involved in the embodiments of this application will be explained. The nouns and terms involved in the embodiments of this application are subject to the following interpretations.

[0021] Bone implant prosthesis matrix: refers to the biocompatible material that constitutes the main structure of the bone implant prosthesis and plays a supporting and filling role. In the embodiments of this application, the matrix material may be, but is not limited to, widely used clinical polymers with good biocompatibility and mechanical properties such as polyetheretherketone (PEEK), polyaryletherketone (PAEK), and polyamide (PA), or biodegradable polymers such as polylactic acid (PLA) and polyglycolic acid (PGA).

[0022] Magnetic particles: These are functional components that are incorporated into the matrix of the bone implant prosthesis in a specific manner to generate a specific magnetic field distribution within the implant to achieve a functional purpose. These particles are biocompatible and may be, for example, nanoscale strontium ferrite, barium ferrite, or iron(III) oxide (Fe3O4) particles, which form specific microstructures in the prosthesis to generate a magnetic field gradient for capturing drugs.

[0023] Chain-like structure: This refers to a microscopic arrangement resembling a chain, formed by multiple magnetic particles arranged in an orderly manner along the direction of the energy field within a specific region of the bone implant matrix during a specific fabrication process, induced by an external energy field (such as a magnetic field). This ordered chain-like structure is the key physical basis for achieving an efficient magnetic field gradient with low magnetic particle content in this application.

[0024] Magnetized drugs are pharmaceutical preparations that combine therapeutic drugs that do not possess magnetic responsiveness or only possess weak magnetic responsiveness with magnetic markers (such as superparamagnetic iron oxide nanoparticles) through physical adsorption or chemical coupling. This process allows the drug to respond to external or implant-derived magnetic field gradients in the bloodstream, achieving targeted aggregation to specific areas.

[0025] Directional magnetic field: This refers to a magnetic field with a specific direction and intensity applied to the molten or semi-molten molding material containing magnetic particles during the 3D printing process of bone implants. The core function of this magnetic field is to act as a driving force, inducing the originally randomly distributed magnetic particles to overcome the viscous resistance of the material, to migrate and rotate in a directional manner, and finally assemble into the aforementioned chain-like structure.

[0026] Pulsed magnetic field: refers to a magnetic field whose intensity changes rapidly and discontinuously over time. In some embodiments of this application, the pulsed magnetic field is used as an initial "activation" method. Its high-intensity instantaneous magnetic field can effectively overcome the initial inertia of magnetic particles and the random orientation of magnetic domains, inducing the magnetic domains of magnetic particles to generate an initial, roughly uniform orientation, laying the foundation for subsequent fine alignment.

[0027] A constant magnetic field is a stable magnetic field whose intensity and direction remain unchanged during the duration of its action. In some embodiments of this application, a constant magnetic field is applied immediately after a pulsed magnetic field. Its function is to use a stable and continuous magnetic force to drive the magnetic particles that have already obtained their initial orientation to complete macroscopic spatial displacement, and ultimately to arrange them closely together and assemble them into an ordered and stable chain structure.

[0028] like Figure 1 As shown, this application provides a bone implant prosthesis 100, which aims to solve the problems of uncontrollable drug release from bone implant materials and poor targeting of traditional intravenous drug delivery in the prior art. The bone implant prosthesis 100 includes a bone implant prosthesis matrix 110 and a plurality of biocompatible magnetic particles 120. The magnetic particles 120 are doped or coated in a designated area of ​​the bone implant prosthesis matrix 110 and form a chain structure in the designated area to generate a magnetic field gradient for capturing magnetized drugs; the axis of the chain structure is consistent with the direction of the magnetic moment vector of the magnetic particles; the mass of the magnetic particles is 0.5%-5% of the total mass of the bone implant prosthesis, and the overall magnetic field strength of the bone implant prosthesis is ≤5mT.

[0029] The key to this embodiment lies in the fact that the magnetic particles are not uniformly and randomly distributed throughout the entire matrix, but are deliberately doped or coated within pre-planned areas of the matrix. Within these areas, the magnetic particles do not exist in isolation, but form a special microscopic arrangement—a chain structure. Furthermore, the axis of this chain structure, i.e., the direction in which the particles are arranged in chains, is aligned with the direction of the magnetic moment vector of the magnetic particles themselves. This chain structure allows for a significant spatial rate of change in magnetic field strength at the microscale, i.e., a high magnetic field gradient, even with very low levels of magnetic particles. It is this high magnetic field gradient that enables the bone implant prosthesis to generate an effective magnetic force on magnetically labeled drug molecules flowing through this area, causing them to separate from the blood and accumulate on the prosthesis surface.

[0030] Magnetic particles 120 can be doped or coated in a designated area of ​​the bone implant prosthesis matrix 110. Doping means that the magnetic particles are located inside the bone implant prosthesis matrix, while coating means that the magnetic particles are located on the surface of the bone implant prosthesis matrix. As long as the magnetic particles can form a chain-like structure to create a magnetic field gradient for capturing magnetized drugs, they can be located inside or on the surface of the bone implant prosthesis matrix.

[0031] To ensure the safety of the bone implant in the human body, and especially to ensure compatibility with modern imaging techniques such as magnetic resonance imaging (MRI), this application strictly limits the amount of magnetic particles and the overall magnetic effect. Specifically, the mass of the magnetic particles as a percentage of the total mass of the bone implant is controlled within a low range, namely 0.5% to 5%. When the amount added is less than 0.5%, even if a chain-like structure is formed, the resulting magnetic field gradient is insufficient to effectively capture the flowing magnetized drug. When the amount added is greater than 5%, on the one hand, the overall magnetic field strength of the material will be too high, which will begin to interfere with MRI examinations; on the other hand, the excessively high content of magnetic particles will affect the mechanical properties and processing properties of the polymer matrix. Therefore, 0.5% to 5% is a preferred range that balances functionality, safety, and processability.

[0032] Meanwhile, by controlling the type, content, and magnetization state of the particles, the overall magnetic field strength of the entire bone implant prosthesis is ensured to be no greater than 5mT. This micromagnetic property makes the prosthesis almost indistinguishable from traditional non-magnetic prostheses when not being targeted for drug delivery, and will not interfere with the patient's daily life or necessary medical examinations.

[0033] For example, the size of the magnetic particles can be controlled in the nanometer to submicrometer range to facilitate uniform dispersion and directional migration in molten polymer materials, thereby ensuring the formation of chain-like structures.

[0034] Magnetic particles can be induced by an external magnetic field to connect end-to-end in a molten matrix, forming a microscopically ordered chain structure along the magnetic field direction. This structure differs from the traditional randomly distributed aggregates of magnetic particles, possessing specific directionality and continuity. Therefore, local magnetic field enhancement regions are generated at the ends of the chain structure, forming a high magnetic field gradient, which can be used to capture magnetized drugs. The magnetic moment vector direction refers to the direction of the magnetic dipole moment of each magnetic particle. In the chain structure, the magnetic particles are connected end-to-end, and the magnetic moment directions of each particle are basically consistent and aligned with the axis of the chain structure.

[0035] For example, the magnitude of the magnetic field gradient formed by the chain structure in this application embodiment is not particularly limited, as long as it is higher than that of the bone implant matrix without the chain structure or the bone implant matrix without magnetic particles. This is because the chain structure forms a magnetic field gradient within a set area. When the magnetized drug flows through the prosthesis with the blood circulation, it is captured by the magnetic force directed towards the chain structure. At the same time, since the drug circulates repeatedly in the blood, a portion is captured each time it flows through, eventually forming a local high concentration of magnetized drug in the set area. This cumulative mechanism allows for significant targeted aggregation even if the magnetic field gradient is small and the single capture efficiency is limited, the long-term cumulative effect can still achieve significant results. For example, the local magnetic field gradient of the chain structure can be 10 to 50 T / m.

[0036] Magnetic particles 120 can be doped or coated onto a designated area of ​​the bone implant matrix 110. The designated area refers to a specific location on the bone implant where the magnetic particles are doped or coated. For example, when the effect of a magnetic drug is to promote bone fusion, the designated area can be the site where bone fusion promotion is desired. The designated area can be pre-designed using 3D printing software according to clinical needs, and it can be all or part of the bone implant.

[0037] In some embodiments, the defined region is the two ends of the bone implant prosthesis matrix.

[0038] In this embodiment, the designated area of ​​the bone implant prosthesis is specifically defined as the two ends of the bone implant prosthesis base. This design has clear clinical application value, particularly suitable for scenarios such as the repair of long bone defects in children. In such scenarios, it is usually necessary to promote rapid fusion with the host bone at the two ends of the prosthesis, while the middle part of the prosthesis may need to be equipped with an extendable device to accommodate the child's growth, and bone ingrowth is undesirable. By limiting the magnetic area to the two ends, when the magnetized osteogenic drug is injected, the drug will only accumulate at the two ends of the prosthesis, achieving differentiated osteogenesis. That is, osteogenesis is precisely promoted at the site where fusion is needed, while there is no drug effect in the middle part where osteogenesis is not needed, thus well matching such complex clinical needs.

[0039] For example, the size of the magnetic regions at both ends can be adjusted according to clinical needs. For instance, in the repair of femoral bone defects in children, magnetic regions of 5 to 10 millimeters can be set at each end, with the middle section made of pure polyetheretherketone material.

[0040] In some embodiments, to achieve more precise regulation of biological effects, the density of the magnetic particles can be designed to be non-uniformly distributed. Specifically, such as Figure 1 As shown, the density of the magnetic particles can exhibit a gradient decreasing distribution from both ends of the bone implant prosthesis matrix towards the middle. The technical advantage of this design is that it creates a gradient-changing drug capture capability on the prosthesis, with the strongest drug accumulation at both ends and gradually decreasing towards the middle.

[0041] This embodiment achieves the following effects: First, it can simulate the physiological state of the growth factor concentration gradient distribution during the natural bone tissue healing process, potentially inducing a more natural bone integration interface with superior mechanical properties, thus meeting the need for more precise control over the osteogenic process. Second, the higher the density of the magnetic particles, the greater the magnetic field gradient generated by their chain structure, and the stronger the ability to capture magnetized drugs. When the density of the magnetic particles is designed to be non-uniformly distributed, the distribution of magnetized drugs in the bone implant prosthesis can be controlled by adjusting the density of the magnetic particles, providing flexible solutions for different patients, different sites, and different treatment goals.

[0042] In some embodiments, the magnetic particles include soft magnetic particles and hard magnetic particles, wherein the hard magnetic particles are used to provide a magnetic field gradient after magnetization; the soft magnetic particles are used to assist in constructing a chain-like structure; and the molar ratio of soft magnetic particles to hard magnetic particles is 1:9-1:11.

[0043] Soft magnetic materials refer to magnetic materials with a coercivity of less than or equal to 1000 A / m, characterized by easy magnetization and demagnetization, narrow hysteresis loops, and high permeability. Hard magnetic materials, also known as permanent magnet materials, refer to magnetic materials with a coercivity greater than 1000 A / m, characterized by the ability to maintain magnetism for a long time after magnetization, wide hysteresis loops, and high remanent magnetic induction. Through the exchange coupling between soft and hard magnetic phases, comprehensive magnetic properties that are difficult to obtain with a single phase can be achieved. In some specific implementation schemes, soft magnetic particles can be selected from ferrite materials with low coercivity, such as nickel-zinc ferrite, manganese-zinc ferrite, or cobalt ferrite; hard magnetic particles can be selected from permanent magnet materials with high coercivity, such as strontium ferrite, barium ferrite, or neodymium iron boron materials.

[0044] Hard magnetic particles (such as strontium ferrite) possess high coercivity and, after magnetization, can provide a stable and persistent magnetic field gradient, serving as the primary source of drug capture. Soft magnetic particles (such as Fe3O4), on the other hand, have lower coercivity and higher permeability. They are more easily magnetized and moved in a directional magnetic field, acting as a "connector" and "guide," assisting hard magnetic particles in constructing a chain-like structure more quickly and systematically. This synergistic effect of these two types of particles optimizes the preparation process while ensuring the final magnetic properties. Specifically, during the preparation process, soft and hard magnetic particles each perform different functions and work synergistically. Hard magnetic particles, as the primary provider of the magnetic field gradient, maintain strong remanent magnetization after magnetization by an external magnetic field, serving as the core source of localized high magnetic field gradients at the ends of the chain-like structure. Soft magnetic particles, due to their low coercivity and fast magnetization response, can be rapidly magnetized in the initial stage of applying a magnetic field, quickly unifying the magnetic moment direction and forming a preliminary chain-like framework, providing guidance for the directional alignment of the hard magnetic particles. This synergistic mechanism of soft magnetic leader and hard magnetic body enables the formation of a more ordered and stable chain structure with the same total amount of magnetic particles added.

[0045] Preferably, the molar ratio of soft magnetic particles to hard magnetic particles is between 1:9 and 1:11. This ratio range has been found to effectively balance preparation efficiency and final magnetic properties. When the proportion of soft magnetic particles is too small, they are unable to effectively guide the formation of the magnetic field, resulting in decreased response speed and alignment consistency of the hard magnetic particles in the applied magnetic field, and reduced efficiency in forming chain structures. When the proportion of soft magnetic particles is too large, the soft magnetic phase content is too high. Although the chain structure may form faster, the tendency of soft magnetic particles to demagnetize leads to a decrease in the stability of the overall magnetic field gradient and may weaken the magnetic field strength dominated by the hard magnetic particles.

[0046] As previously mentioned, magnetic particles 120 can be doped or coated onto a designated area of ​​the bone implant prosthesis matrix 110.

[0047] In the scheme where magnetic particles 120 are incorporated into a designated area of ​​the bone implant matrix 110, the magnetic particles are distributed throughout the entire volume of the matrix. The bone implant 100 can be prepared by mixing the matrix material and magnetic particles 120 in a predetermined ratio, then melt-blending and granulating the mixture using equipment such as a twin-screw extruder to obtain a composite material with uniformly dispersed magnetic particles. This composite material is then 3D printed into a bone implant. During printing, a directional magnetic field is applied to induce the magnetic particles within the designated area to form a chain-like structure. In the scheme where magnetic particles 120 are coated onto a designated area of ​​the bone implant matrix 110, the magnetic particles are distributed on the surface of the matrix. The bone implant 100 can be prepared by first using a pure matrix material to form the main structure of the bone implant matrix 110 using a 3D printing process. Subsequently, a coating material containing magnetic particles 120 is prepared; this coating material can be a polymer solution, slurry, or melt containing magnetic particles. A magnetic coating is formed by selectively applying coating materials to a designated area of ​​the substrate 110 through methods such as spraying, dipping, brushing, or 3D printing micro-jetting. During the coating process, a directional magnetic field is applied to the coating area to induce the magnetic particles to form a chain-like structure.

[0048] The following describes the preparation method 200 of the former type of bone implant prosthesis (i.e., a bone implant prosthesis in which magnetic particles 120 are doped in a designated area of ​​the bone implant prosthesis matrix 110).

[0049] For example, fabrication method 200 can be implemented using a magnetron sputtering 3D printing apparatus 300. The magnetron sputtering 3D printing apparatus 300 is used to fabricate bone implant prostheses with an ordered magnetic flux structure. (Refer to...) Figure 2 The device 300 specifically includes: The feeding module 310, located at the top of the device, continuously and quantitatively pushes composite filaments or granular molding materials to downstream components through the rotation of the feeding gear.

[0050] The 3D printing nozzle 320 is connected to the feeding module and has a longitudinally extending flow channel inside. At the bottom of the flow channel is a nozzle for extruding material.

[0051] Heating module 330 ( Figure 2 (Not shown), which covers or is embedded outside the 3D printing nozzle, is used to heat the molding material in the flow channel to a molten state (e.g., 180-380°C), making the material fluid, thereby allowing the internal magnetic particles to be displaced under the drive of a magnetic field.

[0052] Cargo platform 340 ( Figure 2 (Not shown): Located below the nozzle, it is used to receive the molten material extruded from the nozzle and move along the printing path to solidify and form a prosthesis into a preset shape.

[0053] The magnetic field generating module 350, which is a coil that generates a magnetic field, is the core component of this device. It is used to apply a directional magnetic field to the molding material while it is in a molten state and flowing in the flow channel. This magnetic field generating module is configured to generate a magnetic field of a specific intensity at at least one node along the flow path of the flow channel.

[0054] Method 200 includes the following steps: Step 210: Mix and granulate the raw materials to obtain the molding material; the raw materials include matrix material and magnetic particles for forming the bone implant prosthesis matrix.

[0055] The purpose of this step is to uniformly mix the polymer matrix material with magnetic particles to prepare a granular molding material suitable for 3D printing.

[0056] For example, the raw materials may also include auxiliary raw materials such as dispersants. Dispersants are used to improve the uniform dispersion of magnetic particles in the matrix material and prevent agglomeration.

[0057] For example, the granulation process can be carried out using a twin-screw extruder. The mixed raw materials are heated to a molten state, and the strong shearing action of the screws causes the magnetic particles to be uniformly dispersed in the polymer matrix. Then, the mixture is extruded, cooled, and pelletized to form granular molding materials with a diameter of approximately 2 to 3 millimeters. Granulation is used instead of direct powder mixing for printing because nano- or micron-sized magnetic particles are highly prone to agglomeration. Direct mixing can lead to nozzle clogging, unstable extrusion, and uneven distribution of magnetic particles in the final product. The high shearing force of the twin-screw extruder can fully disperse and uniformly distribute the magnetic particles in the polymer matrix, ensuring the flowability and consistency of the material during subsequent printing. Simultaneously, the granulated material has good flowability and uniform size, making it suitable for the feeding system of fused deposition modeling equipment, enabling continuous and stable feeding.

[0058] Step 220: Feed the molding material into the 3D printing nozzle.

[0059] The purpose of this step is to feed the prepared molding material into the 3D printing system, preparing it for subsequent fused deposition modeling (FDM). In FDM, the molding material is typically fed into the heating chamber of the print head in granular or filament form via gravity or a mechanical feeding mechanism. The feeding process must be continuous and stable to ensure uniform extrusion during printing. The feeding speed can be controlled by the rotational speed of the feed motor, matching the subsequent extrusion speed to avoid printing defects caused by insufficient or excessive material supply.

[0060] Step 230: The molding material is heated to a molten state through the 3D printing nozzle and extruded from the nozzle of the 3D printing nozzle; during the process of the molten molding material flowing in the 3D printing nozzle, a directional magnetic field is applied to the molding material to induce the magnetic particles in the molding material to assemble into a chain structure; and by controlling the extrusion speed of the molding material and the relative moving speed of the 3D printing nozzle, the extruded molten material is deposited along a preset path to form a bone implant prosthesis embryo with the desired shape.

[0061] The relative movement speed of a 3D printing nozzle refers to the relative movement speed between the 3D printing nozzle and the platform supporting the sample. For example, the relative movement speed of the 3D printing nozzle is 1-80 mm / s. The layer thickness of the 3D print is 0.05-0.2 mm.

[0062] Inside the printhead, the molding material is heated to a molten state, making it fluid and ready to be extruded from the nozzle. During this process, as the molten molding material flows from the inside of the 3D printing printhead towards the nozzle, a crucial step is applied: a directional magnetic field is applied to the molding material. For example... Figure 2 As shown, the directional magnetic field induces the directional movement and assembly of suspended magnetic particles in the molten material, ultimately forming the chain-like structure. Simultaneously, by precisely controlling the extrusion speed of the molding material and the relative movement speed of the 3D printing nozzle relative to the printing platform, the printing volume and printing path can be precisely controlled, allowing the extruded molten material to deposit along a preset path, forming a bone implant prosthesis embryo with the desired shape.

[0063] The molding material is heated to a molten state in the print head. The heating temperature is determined according to the type of base material. For example, the printing temperature for polyetheretherketone (PEEK) can be 340 to 380 degrees Celsius, and the printing temperature for polyamide can be 180 to 240 degrees Celsius. The molten material has suitable fluidity, allowing the magnetic particles within it to rotate and move freely within the melt.

[0064] A directional magnetic field is applied during the flow of the molten molding material inside the nozzle. The reason for applying the magnetic field inside the nozzle rather than after extrusion is that the material is still fully molten inside the nozzle, with low viscosity and optimal particle migration ability; once extruded, the material begins to cool and solidify, and the particles are frozen in the matrix, unable to align. The direction of the directional magnetic field can be set as needed; in some embodiments, it is set to be consistent with the material flow direction to reduce the interference of flow shear forces on particle alignment. The function of the directional magnetic field is to induce magnetic particles in the molten material to connect end-to-end along the magnetic field direction, self-assembling into a chain-like structure.

[0065] The application of a directional magnetic field is a key control parameter for achieving the ordered arrangement of magnetic particles. The strength and direction of the magnetic field need to be optimized in conjunction with the material properties, printing process and target structure.

[0066] For example, in this embodiment, the applied magnetic field strength can be adjusted according to the type and amount of magnetic particles, as well as the flow rate of the molten material, as long as effective directional alignment of the magnetic particles can be achieved. It is understood that at higher flow rates, the material's residence time within the magnetic field's area is shorter, requiring a correspondingly higher magnetic field strength to complete particle alignment within a limited time; conversely, at lower flow rates, a relatively lower magnetic field strength can be used. An appropriate magnetic field strength can be selected based on specific process parameters to ensure the efficiency and quality of chain structure formation.

[0067] For example, in this embodiment, the direction of the directional magnetic field is set to be consistent with the flow direction of the molten material in the 3D printing nozzle. For example, the flow direction of the molten material in the 3D printing nozzle is vertically downward, and the magnetic field direction is vertical. This setting has the following advantages: First, when the magnetic field direction is consistent with the flow direction, the magnetic force on the magnetic particles is parallel to the flow direction, making it easier for the particles to connect end-to-end along the flow direction during the flow process, forming an axially aligned chain structure. Second, the consistency of the magnetic field direction with the flow direction can reduce the interference of flow shear force on particle arrangement. If the magnetic field direction is perpendicular to the flow direction, the particles will be subjected to a magnetic force perpendicular to the flow direction, which may cause deflection or tumbling during the flow, hindering the formation of long-range ordered chains. Third, the magnetic field consistent with the flow direction can help the particles overcome the viscous resistance of the melt; when the magnetic force is in the same direction as the flow direction, there is a superposition effect, which can improve the migration speed and arrangement efficiency of the particles.

[0068] For example, the directional magnetic field includes a pulsed magnetic field and a constant magnetic field. The pulsed magnetic field is used to induce the magnetic domains of the magnetic particles to generate an initial orientation; the constant magnetic field is used to drive the magnetic particles to complete spatial displacement and assemble into a chain structure.

[0069] For example, the directions of both the pulsed magnetic field and the constant magnetic field are consistent with the flow direction of the molten material in the 3D printing nozzle, and the magnetic field strength is 50-500 mT. The frequency of the pulsed magnetic field is 0.1-10 Hz (low-frequency repetitive pulse).

[0070] The technical advantage of this dual-mode magnetic field application strategy lies in its decomposition of the orientation and assembly process of magnetic particles into two stages, thereby achieving more efficient and stable control. The first applied pulsed magnetic field, with its instantaneous high intensity, quickly breaks the random state of the particle magnetic domains, providing them with an initial, roughly uniform orientation. The subsequent application of a constant magnetic field, within a relatively stable force field environment, drives these pre-treated particles to complete their final spatial displacement and close alignment, forming a high-quality chain structure. Compared to a single magnetic field, this combined approach achieves better alignment results with lower overall energy consumption.

[0071] For example, when the directional magnetic field includes a pulsed magnetic field and a constant magnetic field, applying the directional magnetic field to the molding material in step 230 during the flow of the molten molding material in the 3D printing nozzle includes: At the first node in the flow path of the molding material, a pulsed magnetic field is applied to the molding material, and at the second node in the flow path of the molding material, a constant magnetic field is applied to the molding material; the molten molding material flows through the first node first, and then through the second node.

[0072] like Figure 2 As shown, when the molding material flows within the 3D printing nozzle, it will inevitably flow through the first node first, and then through the second node, thus ensuring the timing of the application of the pulsed magnetic field followed by the constant magnetic field. This spatial separation design simplifies the complexity of controlling the magnetic field in a time sequence.

[0073] When the molten material has not yet flowed through the nodes affected by the magnetic field, the magnetic domains within the doped hard magnetic particles are arranged in a random and disordered state, exhibiting macroscopic non-magnetic behavior. When the material flows through the first node, the magnetic field generating module applies a high-intensity directional pulsed magnetic field. This instantaneous high-energy magnetic field overcomes the magnetocrystalline anisotropy of the hard magnetic particles, causing the magnetic domains within the particles to rotate uniformly, thus completing the saturation magnetization of the hard magnetic particles in one go, giving them stable remanence and a unified magnetization direction. The material continues to flow downwards to the second node near the nozzle, where the magnetic field generating module applies a steady-state constant magnetic field. Since the material is still in a molten state, the magnetized hard magnetic particles are equivalent to tiny permanent magnets. Under the traction of the applied constant magnetic field, they overcome the viscous resistance of the matrix through magnetic interaction and undergo directional displacement; simultaneously, the soft magnetic particles are induced to magnetize in the magnetic field, generating magnetic dipole moments. Under the combined action of the strong local magnetic field generated by the hard magnetic particles and the applied magnetic field, the soft and hard magnetic particles self-assemble at the microscale through magnetic attraction, aligning along the magnetic field lines to form anisotropic chain-like magnetic domain structures. In subsequent steps, after the molding material undergoes continuous magnetization treatment at the two nodes mentioned above, molten droplets with ordered magnetic chains are extruded from the nozzle onto the carrier platform and rapidly cooled and solidified, thereby permanently locking the microscopic ordered chain structure within the designated area of ​​the bone implant prosthesis.

[0074] Understandably, the first and second nodes are physically spaced apart. Furthermore, when the magnetic particles are a mixture of soft and hard magnetic particles, the distance between the first and second nodes can be optimized. This distance is determined based on the ratio of the soft to the hard magnetic particles. The underlying physical logic is that soft magnetic particles respond to magnetic fields faster and require less time to align. Therefore, a higher proportion of soft magnetic particles means better magnetic responsiveness of the entire particle system, resulting in a shorter time and spatial distance required for alignment, thus allowing for a shorter distance between the first and second nodes. Conversely, a higher proportion of hard magnetic particles leads to a slower system response, requiring a longer constant magnetic field distance for assembly, necessitating a longer node spacing. This design allows the fabrication process parameters to be matched with the material composition, achieving adaptive optimization of the process.

[0075] By precisely controlling the extrusion speed of the molding material and the relative movement speed of the 3D printing nozzle relative to the printing platform while applying a magnetic field, the printing volume and printing path can be precisely controlled, allowing the extruded molten material to deposit along a preset path to form a bone implant prosthesis preform with the desired shape. The extrusion speed determines the volume of material extruded per unit time, and the movement speed determines the linear density of the material deposited per unit length; the values ​​of both control the thickness and width of the deposited layer.

[0076] Step 240: The bone implant prosthesis embryo is solidified and shaped to form a bone implant prosthesis.

[0077] When molten material containing oriented magnetic particles is extruded through a nozzle and deposited at a designated location, it rapidly cools and solidifies due to the decrease in temperature. As the printing process accumulates layer by layer, a bone implant prosthesis with a specific magnetic region distribution and internal microstructure is eventually formed.

[0078] This preparation method integrates macroscopic morphology construction with microscopic structure control, which is the core process guarantee for realizing the function of the bone implant prosthesis described in this application.

[0079] In some embodiments, there are at least two molding materials, and the magnetic particles in the at least two molding materials have different densities.

[0080] The magnetic particle densities in these two or more molding materials are different; for example, one molding material contains high-density magnetic particles, and the other contains low-density or no magnetic particles. In the feeding step, the feeding speed of each of the at least two molding materials entering the 3D printing nozzle is precisely controlled by the feeding module. When printing different areas, the feeding speeds of different materials are dynamically adjusted, in conjunction with the control of the extrusion speed and the print head movement speed, to form a bone implant prosthesis preform with the desired shape and magnetic particle density distribution. For example, bone implant prostheses with designated areas at both ends of the bone implant prosthesis matrix can be prepared, or bone implant prostheses with the magnetic particle density gradually decreasing from both ends of the bone implant prosthesis matrix towards the middle of the bone implant prosthesis matrix.

[0081] Step 220 includes controlling the feed rate when at least two molding materials are fed into the 3D printing nozzle.

[0082] Understandably, after the two molding materials are fed in and mixed, they are extruded through the same 3D printing nozzle. The feeding speed of at least two molding materials can be adjusted to adjust the density of magnetic particles in the extruded molding material.

[0083] Step 230 involves controlling the extrusion speed of the molding material and the relative movement speed of the 3D printing nozzle to deposit the extruded molten material along a preset path to form a bone implant prosthesis preform with the desired shape. This includes controlling the feeding speed of at least two molding materials when they are fed into the 3D printing nozzle, the extrusion speed of the molding material, and the relative movement speed of the 3D printing nozzle to deposit the extruded molten material along a preset path to form a bone implant prosthesis preform with the desired shape and magnetic particle density distribution.

[0084] For example, of at least two molding materials, one contains magnetic particles and the other does not. When preparing a bone implant prosthesis for a designated area, the molding material containing magnetic particles is printed; when preparing a bone implant prosthesis for a non-designated area, the molding material without magnetic particles is printed. For example, of at least two molding materials, one contains magnetic particles and the other does not. When it is desired to prepare a bone implant prosthesis with a magnetic particle density gradient, the designated area with the highest density can be entirely equipped with the molding material containing magnetic particles, then the proportion of the molding material containing magnetic particles can be gradually reduced, the proportion of the molding material without magnetic particles can be increased, and the non-designated area can be entirely equipped with the molding material without magnetic particles.

[0085] Understandably, by selectively opening and closing the directional magnetic field during the printing process, regions with disordered magnetic particles and no magnetic field gradient (formed when the directional magnetic field is closed and no magnetic field is applied to the molten molding material) and regions with high magnetic field gradient (formed when the directional magnetic field is applied to the molten molding material) can be formed.

[0086] Another embodiment of this application provides a drug delivery method 400, which includes the following steps: Step 410: Implant the bone implant prosthesis of the foregoing embodiments of this application or the bone implant prosthesis prepared according to the foregoing preparation method into the patient's body.

[0087] In this step, a surgical procedure is required to implant the bone implant prosthesis described in any of the aforementioned embodiments, or the bone implant prosthesis prepared by the aforementioned preparation method, into the bone defect or other areas requiring treatment within the patient's body.

[0088] Step 420: The magnetized drug is intravenously injected into the patient to capture the magnetized drug circulating through the bone implant prosthesis under the drive of blood circulation by utilizing the magnetic field gradient generated by the magnetic particles in the bone implant prosthesis.

[0089] Among these, drugs can be osteogenic drugs (such as bone morphogenetic protein BMP), anti-infective drugs (such as vancomycin), and anti-tumor drugs (such as cisplatin). Magnetized drugs are drugs that bind to magnetic markers through physical adsorption or chemical coupling.

[0090] The purpose of this step is to administer the drug via conventional intravenous injection, utilizing the magnetic properties of the prosthesis to target and accumulate the drug around the implant. The magnetized drug can be prepared using methods known in the art, such as loading superparamagnetic iron oxide nanoparticles onto the surface of drug molecules through physical adsorption, or covalently linking a magnetic label to the drug molecule via chemical coupling. The magnetic label is typically selected from materials with good biocompatibility and magnetic responsiveness, such as nanoscale iron(III) oxide or ferrite particles. These particles must be small enough to avoid the risk of embolism, while also possessing sufficient magnetic responsiveness to be captured by the magnetic field gradient of the prosthesis.

[0091] Following intravenous injection, the magnetized drug enters the bloodstream and circulates throughout the body. When the drug flows through the area where the implant is located, the local magnetic field gradient generated by the chain-like structure within the implant exerts a magnetic force on the magnetic markers on the drug, pulling them out of the bloodstream and adhering them to the surface of the implant and surrounding tissues. Because the drug continuously circulates within the body, a portion is captured each time it flows past the implant. After multiple cycles, a high-concentration local area of ​​drug forms around the implant, while the drug concentration in other parts of the body remains at a lower level. This cumulative mechanism results in a significantly higher local drug concentration than systemic administration at the same dose, thereby improving efficacy and reducing systemic adverse reactions.

[0092] This administration method also offers significant flexibility and adjustability. Since intravenous injection is a routine clinical route of administration, requiring no special equipment or training, clinicians can flexibly determine the timing, frequency, and dosage of administration based on changes in the patient's condition. For example, in the early postoperative period when intensive osteopromoting therapy is needed, administration can be given weekly; when the risk of infection increases, anti-infective drugs can be temporarily added; and administration can be discontinued at any time when the patient is recovering well. This on-demand flexibility is unattainable with traditional drug-loaded sustained-release implants, which, once implanted, have a fixed drug release behavior that cannot be adjusted according to the patient's condition.

[0093] Through the above-described drug delivery method, this technical solution achieves the following effects: First, it achieves local targeted drug accumulation, increasing the effective drug concentration around the implant and enhancing the therapeutic effect. Second, it reduces systemic drug exposure, decreasing the risk of systemic adverse reactions such as liver and kidney damage and drug resistance. Third, it retains the clinical convenience of intravenous administration, allowing physicians to flexibly adjust the dosing regimen without requiring additional trauma to the patient.

[0094] In some embodiments, the axial direction of the chain structure is parallel to the blood flow direction when the magnetized drug flows through the bone implant prosthesis.

[0095] This setup is based on an in-depth analysis of the drug capture mechanism. When the axis of the chain structure is parallel to the blood flow direction, with both ends of the chain structure pointing upstream and downstream respectively, the drug, as it flows through the prosthesis with the blood flow, is primarily affected by the magnetic force from the ends of the chain structure. Due to the relatively weak magnetic field gradient on the sides of the chain structure, drug capture mainly occurs instantaneously as it flows through the chain ends. Although the capture efficiency for a single pass may not be as high as in the vertical direction, this setup offers the following advantages.

[0096] First, when the chain-like structure is parallel to the blood flow direction, the probability of the drug encountering the ends of the chain-like structure is higher when moving along the blood flow direction, especially when the blood flow velocity is high, as the drug moves along the streamline and is more easily captured by the ends. Second, this arrangement allows the chain-like structure to extend along the prosthesis axis, providing continuous magnetic guidance for the drug over a longer distance, promoting drug accumulation towards the prosthesis ends. Third, for applications requiring directional drug distribution along the prosthesis axis, such as in long bone defects where the drug needs to preferentially concentrate at both ends of the prosthesis to promote fusion with autologous bone, the parallel-arranged chain-like structure can generate an axial magnetic gradient, guiding the drug migration towards the ends.

[0097] It is important to emphasize that the core of this invention is not to pursue maximum efficiency in a single capture, but to achieve significant therapeutic effects by utilizing the repetitive nature of blood circulation and the cumulative effect of magnetic capture. Regardless of the axial direction of the chain structure, as long as the magnetic field gradient it generates is higher than that of a non-magnetic implant, effective targeted drug accumulation can be achieved through multiple cycles. Therefore, the axial direction of the chain structure can be optimized based on the blood flow direction of the specific anatomical site, the prosthesis shape, and the treatment target, rather than being fixed.

[0098] In some specific implementation schemes, the axial direction of the chain structure can be pre-defined based on the anatomical characteristics of the implantation site. For example, in the long bone shaft, where blood flow is mainly along the long axis of the bone, the axial direction of the chain structure can be set parallel to the long axis. In the vertebral body, where blood flow is more complex, the direction can be optimized based on the blood flow characteristics of the specific segment. In the joint, the appropriate arrangement direction can be selected based on the changes in blood flow during joint movement. Through preoperative imaging data and hemodynamic simulation, personalized designs can be made for different patients and different implantation sites to achieve the best drug capture effect.

[0099] In some embodiments, an external magnetic field is applied outside the patient to the region corresponding to the bone implant prosthesis to enhance the capture efficiency of the magnetized drug.

[0100] The intensity of the external magnetic field can be controlled within the range of 5 to 50 millitalas, and its direction can be set to align with or form an angle with the axis of the chain-like structure within the prosthesis to enhance the capture efficiency of magnetized drugs. The external magnetic field can be applied during intravenous injection or for a period afterward, further improving the accumulation efficiency of drugs around the prosthesis by enhancing the local magnetic field gradient. The external magnetic field can be designed as a wearable device, worn by the patient during drug administration and removed after administration, without affecting daily life.

[0101] By optimizing the orientation of the chain structure and / or assisting with an external magnetic field, targeting efficiency can be further enhanced to meet the needs of different clinical scenarios.

[0102] The following specific embodiment describes a fully magnetic bone implant prosthesis and its application provided in this application. This embodiment is suitable for scenarios such as adult limb bone defect repair requiring overall promotion of osteogenesis around the implant and prevention of infection. In preparation, PEEK powder is first mixed with 2% (by mass) strontium ferrite magnetic particles and granulated. Then, the bone implant prosthesis is fabricated using 3D printing technology. During the printing process, a directional magnetic field is applied throughout the entire printing area of ​​the prosthesis, making the entire prosthesis a defined area containing a chain-like structure of magnetic particles. The porosity of the prosthesis is designed to be 40%-60% to facilitate bone ingrowth. After the implantation surgery, starting from the first week post-surgery, the patient is given weekly intravenous injections of a mixture of magnetized bone morphogenetic protein (BMP) and vancomycin for four consecutive weeks. The drugs are efficiently captured around the prosthesis, simultaneously promoting osteogenesis and preventing infection. The physician can decide to stop or extend the administration period at any time based on the patient's recovery, demonstrating high flexibility.

[0103] The following is a further specific embodiment of a locally magnetic bone implant prosthesis and its application. This embodiment is particularly suitable for cases of femoral long bone segment defects in children, where the prosthesis requires fusion of the two ends with autologous bone, while the middle segment remains non-ossified to accommodate an extendable device. During fabrication, the aforementioned multi-material, dual-modal magnetic field-controlled 3D printing process is employed. Only a 5mm region at each end of the prosthesis is printed using PEEK material containing 2% Fe3O4 magnetic particles, and a pulsed-constant combination of directional magnetic fields is applied during printing to form an efficient chain-like structure. The middle segment of the prosthesis is printed using pure PEEK material without magnetic particles. Following the implantation surgery, starting in the second week post-surgery, the patient is intravenously injected with magnetized BMP every two weeks. The drug is captured and enriched only in the magnetic regions at both ends of the prosthesis, precisely promoting bone fusion at both ends, while no drug accumulates in the non-magnetic region in the middle, thus not affecting the subsequent function of the extendable device and achieving precise osteogenic regulation.

[0104] To verify the technical effects of the present invention, the applicant conducted systematic performance tests and animal experiments on the prepared bone implant prosthesis, specifically including material performance verification, targeting efficiency verification, therapeutic effect verification, and drug delivery flexibility verification.

[0105] In terms of material performance verification, the surface magnetic field strength of bone implant prostheses containing 2% magnetic particles was measured using a Tesla meter. The results showed that the surface magnetic field strength of the samples was controlled below 5 millitalas, meeting the design requirements for micromagnetic properties. In MRI compatibility testing, the samples were placed in a 3.0 Tesla MRI scanner for imaging and compared with traditional polyetheretherketone (PEEK) prostheses. The results showed that the bone implant prosthesis of this invention did not produce significant magnetic susceptibility artifacts and did not significantly interfere with the quality of MRI imaging, demonstrating good clinical examination compatibility. Biocompatibility testing was conducted using cytotoxicity and hemolysis experiments. The cytotoxicity experiment results showed that the material promoted osteoblast proliferation, and the hemolysis experiment results showed that the material did not exhibit a hemolytic reaction, meeting the clinical application requirements for biomedical materials.

[0106] In terms of targeting efficiency verification, a rabbit femoral bone defect model was constructed, and the micromagnetic bone implant material of this invention was implanted into the defect site. Postoperatively, magnetized bone morphogenetic protein drugs were injected intravenously. The concentration of bone morphogenetic protein around the implant was detected by immunohistochemistry and compared with the conventional intravenous drug administration group. The experimental results showed that the drug concentration around the implant in the targeted drug administration group was more than 30% higher than that in the conventional group, proving that the bone implant prosthesis of this invention can effectively capture circulating magnetized drugs and achieve local drug enrichment.

[0107] In terms of verifying the therapeutic effect, animal experiments were conducted to assess the bone-promoting and anti-infection effects. In the bone-promoting effect experiment, bone fusion rate was detected by micro-computed tomography at weeks 4, 8, and 12 post-surgery. The results showed that the bone fusion rate in the targeted drug delivery group was more than 25% higher than that in the traditional intravenous drug delivery group, indicating that local drug enrichment significantly promoted the fusion of the prosthesis and autologous bone. In the anti-infection effect experiment, a bone defect model infected with Staphylococcus aureus was constructed, and magnetized vancomycin was injected intravenously. The bacterial clearance rate around the implant was then measured. The results showed that the bacterial clearance rate in the targeted drug delivery group reached over 90%, while the clearance rate in the traditional intravenous drug delivery group was only about 60%, demonstrating the significant advantages of the targeted drug delivery method of this invention in anti-infection treatment.

[0108] Regarding the verification of dosing flexibility, the flexibility and safety of the dosing method were verified through an experimental design involving multiple start-stop dosing cycles. Different dosing regimens with intervals of 1 week and 2 weeks were set up in the experiment to test the therapeutic effect under different dosing frequencies. The results showed that even with intermittent dosing, the targeted dosing group maintained good therapeutic effects, and no significant systemic adverse reactions were observed. This result proves that the dosing method of the present invention can flexibly adjust the dosing time and frequency according to changes in the patient's condition, overcoming the limitations of fixed dosing methods in traditional drug-loaded implants.

[0109] The experimental data above show that the bone implant prosthesis and its targeted drug delivery method of the present invention exhibit excellent performance in terms of material safety, drug targeting efficiency, therapeutic effect and drug delivery flexibility, and have good potential for clinical translation.

[0110] Principles and steps not explicitly described in this invention are all obtainable by those skilled in the art through conventional technical means, and therefore will not be elaborated upon. Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A bone implant prosthesis, characterized in that, include: Bone implant prosthesis matrix; The device also contains multiple biocompatible magnetic particles, which are doped or coated in a designated area of ​​the bone implant matrix and form a chain-like structure within the designated area to generate a magnetic field gradient for capturing magnetized drugs; the axial direction of the chain-like structure is aligned with the magnetic moment vector direction of the magnetic particles. The mass of the magnetic particles is 0.5%-5% of the total mass of the bone implant prosthesis, and the overall magnetic field strength of the bone implant prosthesis is ≤5mT.

2. The bone implant prosthesis according to claim 1, characterized in that, The designated area refers to both ends of the bone implant prosthesis base.

3. The bone implant prosthesis according to claim 1, characterized in that, The density of the magnetic particles decreases gradually from both ends of the bone implant prosthesis matrix towards the middle of the bone implant prosthesis matrix.

4. The bone implant prosthesis according to claim 1, characterized in that, The magnetic particles include soft magnetic particles and hard magnetic particles. The hard magnetic particles are used to provide the magnetic field gradient after magnetization. The soft magnetic particles are used to assist in constructing the chain structure. The molar ratio of the soft magnetic particles to the hard magnetic particles is 1:9 to 1:

11.

5. A method for preparing a bone implant prosthesis as described in any one of claims 1 to 4, characterized in that, Includes the following steps: The raw materials are mixed and granulated to obtain a molding material; the raw materials include a matrix material for forming the bone implant prosthesis matrix and the magnetic particles. The molding material is fed into the 3D printing nozzle; The molding material is heated to a molten state through a 3D printing nozzle and extruded from the nozzle of the 3D printing nozzle; during the flow of the molten molding material in the 3D printing nozzle, a directional magnetic field is applied to the molding material to induce the magnetic particles in the molding material to assemble into a chain structure; and by controlling the extrusion speed of the molding material and the relative moving speed of the 3D printing nozzle, the extruded molten material is deposited along a preset path to form a bone implant prosthesis embryo with the desired shape; The bone implant prosthesis embryo is solidified and molded to form the bone implant prosthesis.

6. The method according to claim 5, characterized in that, The direction of the directional magnetic field is consistent with the direction of the molten molding material flowing in the 3D printing nozzle.

7. The method according to claim 6, characterized in that, The directional magnetic field includes a pulsed magnetic field and a constant magnetic field. The pulsed magnetic field is used to induce the magnetic domains of the magnetic particles to generate an initial orientation. The constant magnetic field is used to drive the magnetic particles to complete spatial displacement and assemble into a chain structure.

8. The method according to claim 7, characterized in that, During the flow of molten molding material in the 3D printing nozzle, a directional magnetic field is applied to the molding material, including: At the first node on the flow path of the molding material, the pulsed magnetic field is applied to the molding material, and at the second node on the flow path of the molding material, the constant magnetic field is applied to the molding material; the molding material first flows through the first node and then flows through the second node.

9. The method according to claim 8, characterized in that, The magnetic particles include soft magnetic particles and hard magnetic particles, and the molar ratio of the soft magnetic particles to the hard magnetic particles is 1:9-1:11; The interval between the first node and the second node is determined based on the ratio of the soft magnetic particles to the hard magnetic particles. The higher the proportion of the soft magnetic particles, the shorter the interval between the first node and the second node.

10. The method according to claim 5, wherein the molding material comprises at least two types, and the magnetic particles in the at least two molding materials have different densities; The step of feeding the molding material into the 3D printing nozzle includes: Control the feeding speed of the at least two molding materials when they are fed into the 3D printing nozzle; The method of controlling the extrusion speed of the molding material and the relative movement speed of the 3D printing nozzle to make magnetic particles dopant in a designated area of ​​the bone implant prosthesis matrix includes: controlling the feeding speed of the at least two molding materials when they are fed into the 3D printing nozzle, the extrusion speed of the molding material, and the relative movement speed of the 3D printing nozzle to make magnetic particles dopant in a designated area of ​​the bone implant prosthesis matrix at a desired density.

11. A method of administration, characterized in that, The method includes the following steps: The bone implant prosthesis according to any one of claims 1-4 or the bone implant prosthesis prepared by the method according to any one of claims 5-10 is implanted into the patient. The magnetized drug is intravenously injected into the patient to capture the magnetized drug circulating through the bone implant prosthesis under the drive of blood circulation by utilizing the magnetic field gradient generated by the magnetic particles in the bone implant prosthesis. The magnetized drug is a drug with a magnetic marker attached by means of physical adsorption or chemical coupling; the axial direction of the chain structure is parallel to the blood flow direction when the magnetized drug flows through the bone implant prosthesis.

12. The method of administration according to claim 11, characterized in that, Also includes: An external magnetic field is applied outside the patient's body to the region corresponding to the bone implant prosthesis to enhance the capture efficiency of the magnetized drug.

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