A piezoelectrically active smart biodegradable three-dimensional porous scaffold, its preparation method and application

Abstract

This application belongs to the field of biomedical materials technology, and more specifically, relates to a piezoelectrically active intelligent biodegradable three-dimensional porous scaffold, its preparation method, and its application. This application involves ultrasonically mixing a suitable ratio of piezoelectric white calcium phosphate stone and a biodegradable metal material, allowing the piezoelectric white calcium phosphate stone to be uniformly adsorbed onto the surface of the biodegradable metal material via physical adsorption. The resulting composite powder is then 3D printed to prepare a three-dimensional porous scaffold with excellent mechanical properties, good biosafety, sensitive piezoelectric response, and adaptively adjustable degradation rate. This scaffold provides good support for critical bone defects and sensitively detects the stress at the critical bone defect site. Through stress, a microcurrent is generated within the three-dimensional porous scaffold, promoting the degradation of the biodegradable metal material and the formation of new bone. The degradation rate is adaptively adjusted according to the stress magnitude to match the bone remodeling rate, effectively promoting bone remodeling.

Description

Technical Field

[0001] This application belongs to the field of biomedical materials technology, and more specifically, relates to a piezoelectrically active smart biodegradable three-dimensional porous scaffold, its preparation method and application. Background Technology

[0002] Clinically, borderline bone defect disease refers to a pathological state in which the bone structure is severely missing due to trauma, infection, tumor resection or congenital factors, and the defect range exceeds the bone’s own regeneration capacity (usually referring to a length exceeding 2-5 cm or a volume exceeding 50% of the bone diameter) and cannot be repaired through natural healing. It has the following pathophysiological characteristics: (1) bone regeneration disorder; (2) high risk of complications (such as limb deformity, functional impairment, recurrent infection, and increased risk of pathological fracture).

[0003] Currently, the main clinical treatments for borderline bone defects include four types: autologous bone grafting, allogeneic bone grafting, bone transport techniques (Ilizarov technique), and artificial bone substitutes. Autologous bone grafting carries risks such as donor site complications (e.g., pain, infection) and insufficient bone volume. Allogeneic bone grafting carries risks of immune rejection, infection transmission (e.g., HIV, hepatitis viruses), and delayed osseointegration. Bone transport techniques have long treatment cycles (months to years) and numerous complications (pin tract infection, joint contractures). Traditional artificial bone substitutes, such as hydroxyapatite and calcium sulfate, have insufficient mechanical properties, and their degradation rates do not match osteogenesis. Therefore, there is an urgent need to develop novel artificial bone substitutes suitable for repairing borderline bone defects.

[0004] Biodegradable metals have shown great advantages in the development of novel artificial bone replacement materials due to their excellent mechanical properties and have been widely used. Patent document CN119345454A obtained a composite material by uniformly mixing piezoelectric material powders such as tetragonal barium titanate, zinc oxide, and molybdenum sulfide with metal ion-releasing material powder and then laser melting and molding it through 3D printing. However, this composite material suffers from problems such as piezoelectric material delamination or even shedding, poor printability, insufficient mechanical properties, limited bioactive components, insufficient piezoelectric stability, and poor piezoelectric response sensitivity. It cannot effectively adaptively adjust the degradation rate according to the recovery status of patients with critical bone defects.

[0005] White calcium phosphate is a type of magnesium-containing calcium phosphate (WH:Ca). 18 Mg2(HPO4)2(PO4) 12 It has a non-centrosymmetric structure and undergoes domain transformation after annealing and polarization, thus exhibiting piezoelectric properties. Patent document CN119930322A utilizes the crystalline similarity between β-tricalcium phosphate and leucobite, by immersing a porous ceramic scaffold of β-tricalcium phosphate in a Mg-containing... 2+In simulated body fluids, β-tricalcium phosphate is converted into leucobionic calcium phosphate under hydrothermal conditions, thus preparing a leucobionic calcium phosphate ceramic scaffold. Annealing then transforms the leucobionic calcium phosphate ceramic scaffold into a piezoelectric leucobionic calcium phosphate ceramic scaffold. However, the structure of the aforementioned piezoelectric leucobionic calcium phosphate ceramic scaffold is determined by the initial porous β-tricalcium phosphate ceramic scaffold, making it difficult to flexibly control the pore structure or achieve complex personalized designs in subsequent steps. Furthermore, this pure piezoelectric leucobionic calcium phosphate ceramic scaffold is highly brittle and prone to fracture under dynamic stress (such as mechanical loads during human movement), limiting its application in load-bearing components. In addition, the preparation process of the aforementioned piezoelectric leucobionic calcium phosphate ceramic scaffold is complex, time-consuming, and requires strict control of hydrothermal reaction conditions, making large-scale production difficult.

[0006] Therefore, developing a method for preparing intelligent biodegradable three-dimensional porous scaffolds with shape customization, biomimetic function, and excellent mechanical properties that is simple to process, time-saving, and allows for precise control of pore structure is the key and challenging aspect of preparing three-dimensional porous scaffolds for critical bone defects. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this application aims to provide a smart biodegradable three-dimensional porous scaffold with piezoelectric activity, its preparation method, and its application. This aims to solve problems such as insufficient mechanical properties, poor piezoelectric stability and piezoelectric responsiveness, mismatch between scaffold degradation rate and osteogenic rate, and complex, time-consuming, and unsuitable personalized design processes of existing three-dimensional porous scaffolds.

[0008] To achieve the above objectives, in a first aspect, this application provides a method for preparing a piezoelectrically active smart biodegradable three-dimensional porous scaffold, comprising the following steps:

[0009] S1. Ultrasonic mixing of piezoelectric white calcium phosphate and biodegradable metal materials yields composite powder;

[0010] The mass ratio of the above-mentioned piezoelectric white calcium phosphate stone to the above-mentioned biodegradable metal material is (0.5~2):100; the piezoelectric white calcium phosphate stone in the above-mentioned composite powder is attached to the surface of the biodegradable metal material by physical adsorption.

[0011] S2. The above-mentioned composite powder is used to prepare the above-mentioned three-dimensional porous scaffold by 3D printing process.

[0012] Preferably, in step S1, the melting point of the biodegradable metal material is below 900°C.

[0013] More preferably, the aforementioned biodegradable metallic material is selected from one or more of magnesium-based biodegradable alloys, zinc and zinc-based biodegradable alloys, and FeZn series alloys with melting points below 900°C.

[0014] Preferably, the particle size of the above-mentioned biodegradable metal material is 15 µm to 53 µm.

[0015] Preferably, in step S1, the particle size of the piezoelectric white calcium phosphate is 10 nm to 100 nm.

[0016] Preferably, in step S1, the frequency of the ultrasonic mixing is 20 kHz to 60 kHz, and the ultrasonic mixing time is 15 min to 60 min.

[0017] Preferably, in step S2, the 3D printing technology mentioned above is any one of selective laser sintering technology, selective laser melting technology, electron beam melting technology, laser engineered net forming technology, metal binder jetting technology, nanoparticle jetting technology, gel metal printing technology, and digital light processing technology.

[0018] Preferably, the fabrication of a three-dimensional porous scaffold using selective laser melting technology includes the following steps:

[0019] The composite powder is placed in the powder feeder of the laser melting system. Under the protective atmosphere, the composite powder is melted and deposited layer by layer on the forming substrate according to the scanning path and process parameters set by the laser melting system to prepare the three-dimensional porous scaffold.

[0020] Preferably, the process parameters of the above-mentioned laser melting system are: laser power of 150 W to 180 W, scanning speed of 500 mm / s to 900 mm / s, overlap distance of 40 µm to 70 µm, and powder layer thickness of 30 µm to 50 µm.

[0021] Preferably, the protective atmosphere is selected from at least one of argon, nitrogen, and helium.

[0022] Preferably, the oxygen content in the above protective atmosphere is ≤1000 ppm.

[0023] Preferably, the above-mentioned forming substrate is a stainless steel plate or a zirconium alloy plate.

[0024] Secondly, this application provides a smart biodegradable three-dimensional porous scaffold with piezoelectric activity prepared by the above-described preparation method.

[0025] Preferably, the porosity of the above-mentioned three-dimensional porous scaffold is 60%~90%, and the yield strength is 20 MPa~80 MPa.

[0026] Thirdly, this application provides an implant for critical bone defects, which includes the above-described three-dimensional porous scaffold or a three-dimensional porous scaffold prepared by the above-described preparation method.

[0027] In summary, the technical solutions conceived in this application have the following main technical advantages compared with the prior art:

[0028] (1) This application involves ultrasonically mixing piezoelectric white calcium phosphate stone and biodegradable metal materials in appropriate proportions, so that the piezoelectric white calcium phosphate stone is uniformly adsorbed onto the surface of the biodegradable metal materials by physical adsorption. Then, the resulting composite powder is 3D printed to prepare a three-dimensional porous scaffold with excellent mechanical properties, good biosafety, sensitive piezoelectric response, and adaptively adjustable degradation rate. When the above-mentioned three-dimensional porous scaffold is used as an implant for critical bone defects, it can provide good support for the critical bone defect site, and at the same time, it can sensitively detect the stress situation of the critical bone defect site. Through stress, microcurrents are generated in the three-dimensional porous scaffold, which promotes the degradation of biodegradable metal materials and the formation of new bone. The degradation rate is adaptively adjusted according to the magnitude of the stress, so that the degradation rate matches the bone remodeling rate, effectively promoting bone remodeling.

[0029] (2) In practical applications, the structure of the three-dimensional porous scaffold can be precisely designed according to the shape and size of the patient's critical bone defect, making it suitable for different bone remodeling environments and effectively improving the adaptability of the implant. In addition, the porous structure constructed by the three-dimensional porous scaffold provided in this application has a biomimetic function, which can simulate the trabecular bone structure, effectively promote blood vessel ingrowth and osteoblast differentiation, and better promote bone remodeling. Attached Figure Description

[0030] Figure 1 This is a schematic flowchart of the preparation method of the piezoelectrically active smart biodegradable three-dimensional porous scaffold provided in this application;

[0031] Figure 2 Here is the XRD pattern of the PWH particles prepared in the embodiments of this application;

[0032] Figure 3 These are piezoelectric performance test diagrams of PWH particles prepared in the embodiments of this application; wherein content (a) is a piezoelectric response phase hysteresis loop diagram and content (b) is an amplitude butterfly loop diagram;

[0033] Figure 4 These are SEM images of the ZnMg alloy powder and ZnMg / PWH composite powder prepared in Example 1 of this application; wherein content (a) is ZnMg alloy powder and content (b) is ZnMg-PWH composite powder;

[0034] Figure 5 This is a photograph of the ZnMg-PWH porous scaffold prepared in Example 1 of this application;

[0035] Figure 6This refers to the weight loss rate of the ZnMg-PWH porous scaffold prepared in Example 1 of this application under cyclic dynamic load;

[0036] Figure 7 This is a diagram showing the compressive strength of the ZnMg-PWH porous scaffold prepared in Example 1 of this application. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0038] In the description of this application, it should be understood that the term "and / or" describes a relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. The symbol " / " in this document indicates that the related objects are in an "or" relationship; for example, A / B means A or B.

[0039] In the description of the embodiments in this application, the words "exemplary" or "for example" are used to indicate that they are examples, illustrations, or descriptions. Any embodiment or design that is described as "exemplary" or "for example" in the embodiments of this application should not be construed as being more preferred or advantageous than other embodiments or design options. Specifically, the use of the words "exemplary" or "for example" is intended to present the relevant concepts in a specific manner.

[0040] In the description of the embodiments in this application, unless otherwise stated, "multiple" means two or more.

[0041] Tetragonal barium titanate, molybdenum sulfide, and zinc oxide are commonly used piezoelectric materials in the field of biodegradable materials. Among them, tetragonal barium titanate has a perovskite crystal structure, with its basic structural unit being a cubic unit cell. Barium ions are located at the vertices of the cube, titanium ions at the body center, and oxygen ions at the face centers. In the tetragonal phase, the displacement of titanium ions within the oxygen octahedron is key to the piezoelectric effect of tetragonal barium titanate. Molybdenum sulfide has a hexagonal layered crystal structure, with molybdenum and sulfur atoms forming covalent bonds within the layers, and the layers are bonded by relatively weak van der Waals forces. The piezoelectric properties of molybdenum sulfide are closely related to the interlayer interactions and the characteristics of the chemical bonds within the layers. When the layered structure is subjected to stress, the covalent bonds within the layers deform, altering the electron cloud distribution and thus producing a piezoelectric effect. Zinc oxide has a hexagonal wurtzite crystal structure, where zinc and oxygen atoms are arranged alternately, forming a honeycomb-like structure. The asymmetric distribution of zinc and oxygen ions causes zinc oxide to undergo ion displacement and polarization when subjected to stress.

[0042] White calcium phosphate is a calcium phosphate mineral with a unique phosphate crystal structure similar to that of hydroxyapatite, the main component of human bones. White calcium phosphate exhibits excellent biocompatibility and can degrade in physiological environments, releasing magnesium... 2+ Ca 2+ and PO4 3- It can interact with biological tissues and cells and proteins within organisms, regulating cellular biological behaviors, such as promoting osteoblast adhesion, proliferation, and differentiation, which is beneficial for bone defect repair and regeneration. The piezoelectric mechanism of leucobionic calcium phosphate is related to the displacement of ions within the crystal. Under mechanical stress, calcium ions and phosphate ions in the crystal undergo relative displacement, leading to a misalignment of positive and negative charge centers, resulting in polarization and exhibiting piezoelectric properties. These piezoelectric properties are adaptable to the physiological environment within organisms. Compared to common piezoelectric materials such as tetragonal barium titanate, molybdenum sulfide, and zinc oxide, leucobionic calcium phosphate differs in crystal structure, chemical composition, bioactivity, and piezoelectric mechanism. While leucobionic calcium phosphate is a material with unique piezoelectric properties and bioactivity, its piezoelectric response in the microenvironment of organisms has not been fully studied, and it has not been used in 3D printing of porous scaffolds. The performance of leucobionic calcium phosphate in 3D printed structures, such as piezoelectric response sensitivity and piezoelectric stability, remains unpredictable. Furthermore, piezoelectric white calcium phosphate powder exhibits poor flowability, is prone to agglomeration, and has poor interfacial bonding with biodegradable metal materials. Therefore, the key technical problem this application aims to solve is how to achieve intelligent degradation by mixing piezoelectric white calcium phosphate and biodegradable metal materials and then using 3D printing to prepare porous scaffolds with excellent mechanical properties, stable piezoelectric properties, high piezoelectric response sensitivity, and the ability to adaptively adjust the degradation rate based on the recovery status of critical bone defect sites in patients.

[0043] This application provides a method for preparing a piezoelectrically active, intelligent, biodegradable, three-dimensional porous scaffold, such as... Figure 1 As shown, it includes the following steps:

[0044] S1. Ultrasonic mixing of piezoelectric white calcium phosphate and biodegradable metal materials yields composite powder;

[0045] The mass ratio of the above-mentioned piezoelectric white calcium phosphate stone to the above-mentioned biodegradable metal material is (0.5~2):100; the piezoelectric white calcium phosphate stone in the above-mentioned composite powder is attached to the surface of the biodegradable metal material by physical adsorption.

[0046] S2. The above-mentioned composite powder is used to prepare the above-mentioned three-dimensional porous scaffold by 3D printing process.

[0047] The inventors of this application discovered during experiments that the state of the composite powder obtained in step S1 has a significant impact on the subsequent printing process and results of the three-dimensional porous scaffold. If the mixing method is inappropriate, such as using ball milling, the three-dimensional porous scaffold printed using this composite powder will have poor formability and mechanical properties.

[0048] In some embodiments, in step S1, the mixing method is ultrasonic mixing.

[0049] For the mixing of commonly used piezoelectric materials such as tetragonal barium titanate, molybdenum sulfide, and zinc oxide with biodegradable metal materials, the longer the ultrasonic mixing time, the more piezoelectric material is adsorbed on the surface of the biodegradable metal material, and the higher the piezoelectric response sensitivity of the prepared porous scaffold. However, the inventors of this application unexpectedly discovered during the experiment that when ultrasonically treating piezoelectric white calcium phosphate and biodegradable metal materials, excessively high ultrasonic frequency / excessively long time caused the piezoelectric white calcium phosphate originally adsorbed on the surface of the biodegradable metal material to fall off under vibration and friction. This may be related to the poor interfacial bonding between the piezoelectric white calcium phosphate and the biodegradable metal material; excessively low ultrasonic frequency / excessively short time caused a large amount of piezoelectric white calcium phosphate to agglomerate.

[0050] In some embodiments, the frequency of the ultrasonic treatment is 20 kHz to 60 kHz, and the duration is 15 min to 60 min. This application effectively solves the problems of poor flowability, easy agglomeration, and poor interfacial bonding with biodegradable metal materials of piezoelectric white calcium phosphate powder by controlling the mixing method and parameters. The resulting composite powder is suitable as a biomedical metal additive material. Furthermore, a three-dimensional porous scaffold prepared using this composite powder via 3D printing exhibits excellent mechanical properties and can effectively provide support. Simultaneously, the piezoelectric white calcium phosphate is uniformly distributed within the three-dimensional scaffold structure, giving it highly sensitive, durable, and stable piezoelectric response performance. It can adaptively degrade according to the recovery status (i.e., the magnitude of stress) of the critical bone defect site, while simultaneously promoting new bone formation at the bone defect site, making it suitable for regeneration and repair of critical bone defects.

[0051] In some embodiments, the particle size of the above-mentioned piezoelectric white calcium phosphate is 10 nm to 100 nm, preferably 20 nm to 50 nm.

[0052] In some embodiments, the melting point of the aforementioned biodegradable metal material is below 900°C. The inventors of this application have experimentally discovered that when the melting point of the biodegradable metal material is above 900°C, the piezoelectric properties of the three-dimensional porous scaffold prepared by 3D printing using the composite powder obtained by ultrasonically mixing the biodegradable metal material and piezoelectric white calcium phosphate rock disappear.

[0053] In some embodiments, the aforementioned biodegradable metallic material may be selected from one or more magnesium-based biodegradable alloys with a melting point below 900°C, or from one or more zinc and zinc-based biodegradable alloys with a melting point below 900°C, or from one or more FeZn series alloys with a melting point below 900°C.

[0054] In some embodiments, the aforementioned magnesium-based biodegradable alloys with melting points below 900°C are selected from Mg 60 Zn 35 One or more of the following: Ca5 amorphous alloy, MgZnCaSr amorphous alloy, MgZnYNd alloy, MgYReZr alloy, MgZnCa alloy, MgZnSr alloy, MgZnCaSr alloy, and MgZnCu alloy.

[0055] In some embodiments, the zinc-based biodegradable alloys with melting points below 900°C are selected from one or more of the following: ZnMg series alloys, ZnCa series alloys, ZnCu series alloys, ZnMn series alloys, ZnLi series alloys, and ZnRe series alloys. The ZnMg series alloys include, but are not limited to, Zn-0.8Mg, Zn-3Mg, Zn-1Mg-1Sr, Zn-1Mg-0.1Mn, and Zn-1Mg-1Ca. The ZnCa series alloys include, but are not limited to, Zn-1Ca-1Sr. The ZnCu series alloys include, but are not limited to, Zn-3Cu, Zn-3Cu-0.5Fe, and Zn-3Cu-0.5Mg. The ZnMn series alloys include, but are not limited to, Zn-0.1Mn. The ZnLi series alloys include, but are not limited to, Zn-0.4Li, Zn-0.5Li, Zn-0.8Li, and Zn-0.8Li-0.2Ag. The aforementioned ZnRe series alloys include, but are not limited to, Zn-0.2La, Zn-0.2Y, Zn-0.2Ce, Zn-0.2Nd, Zn-0.2Ho, and Zn-0.2Lu.

[0056] In some embodiments, the FeZn series alloys with melting points below 900°C include, but are not limited to, Fe-10Zn, Fe-15Zn, and Fe-20Zn. It should be understood that the numerical values ​​preceding the metallic elements in the above series of alloys represent the mass percentage of that element in the alloy.

[0057] This application does not limit the source of the biodegradable metallic materials. Those skilled in the art can purchase commercially available products or prepare them in their own laboratory, depending on the actual situation. The preparation methods for biodegradable alloy materials include, but are not limited to, vacuum melting to prepare a master alloy ingot followed by atomization powdering, and preparing an alloy liquid followed by atomization powdering. For example, the above-mentioned process for preparing biodegradable alloy materials is as follows: ingredients are prepared according to the composition of the biodegradable alloy material, and the prepared raw materials are vacuum melted into a master alloy ingot. Then, the master alloy ingot is heated until completely melted, and atomized gas is introduced to perform atomization powdering to obtain biodegradable alloy material powder. Another example is that the above-mentioned process for preparing biodegradable alloy materials is as follows: ingredients are prepared according to the composition of the biodegradable alloy material, and the prepared raw materials are vacuum melted into an alloy liquid. Then, atomized gas is introduced to perform atomization powdering to obtain biodegradable alloy material powder.

[0058] This application does not limit the above-described vacuum melting method, such as, but not limited to, vacuum induction melting. Those skilled in the art can select a suitable melting temperature based on the melting point of the alloy.

[0059] In some embodiments, the atomizing gas is any one of inert gases with a purity of 99.99% or higher, wherein the inert gas is one or more of helium (He), argon (Ar), neon (Ne), and krypton (Kr).

[0060] In some embodiments, the pressure of the atomizing gas is 0.2 MPa to 2 MPa.

[0061] In some embodiments, the particle size of the above-mentioned biodegradable metal material is 15 µm to 53 µm.

[0062] It is understood that this application does not limit the 3D printing technology in step S2, such as, but not limited to, any one of selective laser sintering (SLS), selective laser melting (SLM), electron beam melting (EBM), laser engineered net forming (LENS), metal binder jetting (BJ), nanoparticle jetting (NPJ), digital light processing (DLP), and gel metal printing (DLP derivative technology).

[0063] In some embodiments, the fabrication of three-dimensional porous scaffolds using selective laser melting (SLM) includes the following steps:

[0064] The composite powder is placed in the powder feeder of the laser melting system. Under the protective atmosphere, the composite powder is melted and deposited layer by layer on the forming substrate according to the scanning path and process parameters set by the laser melting system to prepare the three-dimensional porous scaffold.

[0065] This application does not limit the above scanning path. In practical applications, a personalized three-dimensional porous scaffold structure can be designed according to the specific bone damage shape of the patient, and then the scanning path can be set accordingly. In some embodiments, the above scanning path is: integral molding, layer-by-layer scanning, with the interlayer rotation angle set to 65°~70° to release residual stress and improve molding quality.

[0066] In some embodiments, the process parameters of the laser melting system are as follows: laser power of 150 W to 180 W, scanning speed of 500 mm / s to 900 mm / s, overlap spacing of 40 µm to 70 µm, and powder layer thickness of 30 µm to 50 µm. Using these process parameters for printing will not affect the piezoelectric response performance of the printed three-dimensional porous scaffold. In actual production, those skilled in the art can select the specific laser power based on the melting point of the aforementioned biodegradable metal material.

[0067] In some embodiments, before setting the process parameters of the laser melting system, the above-mentioned forming substrate is first cleaned, including but not limited to surface cleaning, polishing, sandblasting, ultrasonic cleaning, alcohol cleaning, etc.

[0068] In some embodiments, the above-mentioned molded substrate is a stainless steel plate or a zirconium alloy plate.

[0069] In some embodiments, the cleaned substrate is dried, placed in the forming chamber under a protective atmosphere, and leveled on the worktable of the laser additive manufacturing equipment for later use.

[0070] In some embodiments, the above-mentioned molded substrate is preheated to 100 ℃~150 ℃, and then the above-mentioned composite powder is melted and deposited layer by layer on the molded substrate.

[0071] In some embodiments, the protective atmosphere is selected from at least one of argon (Ar), nitrogen (N2), and helium (He).

[0072] In some embodiments, the oxygen content in the above-mentioned protective atmosphere is ≤1000 ppm.

[0073] In a preferred embodiment, the oxygen content in the protective atmosphere is ≤500 ppm.

[0074] On the other hand, this application provides a smart biodegradable three-dimensional porous scaffold with piezoelectric activity prepared by the above preparation method, namely a personalized smart biodegradable implantable device with piezoelectric activity.

[0075] In some embodiments, the porosity of the above-mentioned three-dimensional porous scaffold is 60%~90%, and the yield strength is 20 MPa~80 MPa. In a preferred embodiment, the porosity of the above-mentioned three-dimensional porous scaffold is 65%~70%, and the yield strength is 25 MPa~60 MPa.

[0076] This application does not have any special limitation on the pore shape of the above-mentioned three-dimensional porous scaffold, which can be, but is not limited to, spherical pores, columnar pores, square pores, mesh pores, curved pores, etc.

[0077] The piezoelectrically active intelligent biodegradable three-dimensional porous scaffold provided in this application has a biomimetic function in its appropriately constructed pore structure, which can simulate the trabecular bone structure, effectively promoting blood vessel ingrowth and osteoblast differentiation, and promoting bone remodeling. Simultaneously, the aforementioned three-dimensional porous scaffold also possesses excellent mechanical properties, providing good support for critical bone defect sites. When used as an implant for critical bone defects, the three-dimensional porous scaffold can sensitively detect the stress at the critical bone defect site, generating microcurrents within it through stress, promoting the degradation of biodegradable metallic materials and the formation of new bone. Furthermore, it adaptively adjusts the degradation rate of the three-dimensional porous scaffold according to the magnitude of the stress at the critical bone defect site, achieving intelligent degradation of the three-dimensional porous scaffold.

[0078] Based on this, this application also provides an implant for critical bone defects, which includes the above-described three-dimensional porous scaffold or a three-dimensional porous scaffold prepared by the above-described preparation method.

[0079] It should be understood that materials of the same or similar type, model, quality, properties, or function as the reagents and instruments used in the following embodiments can be used to implement this application. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available.

[0080] The following are examples and comparative examples:

[0081] Example 1

[0082] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0083] (1) Preparation of Zn-0.8Mg alloy powder

[0084] The Zn-0.8Mg alloy powder designed in this embodiment comprises 99.2% Zn and 0.8% Mg by mass percentage. The raw materials, metallic zinc and metallic magnesium, are prepared according to the above proportions, with each raw material having a purity of over 99.9%. The raw materials are then placed in an induction melting furnace and evacuated to a vacuum of 8 × 10⁻⁶. -3After Pa, high-purity argon gas (99.99% purity) is introduced into the furnace until the relative pressure in the chamber reaches -0.05 MPa for vacuum induction melting. Once the zinc and magnesium are completely melted and uniformly mixed to form a liquid metal alloy, the molten alloy is introduced into the atomization chamber through a guide tube. Then, high-pressure argon gas (0.4~0.6 MPa) is ejected at high speed through a nozzle, impacting the molten metal flow and tearing it into tiny droplets. These droplets rapidly cool within the atomization chamber, and surface tension causes them to form spherical powder. Finally, after sieving and grading, biodegradable Zn-0.8Mg alloy powder with a particle size of 15~53 µm is obtained, referred to as ZnMg alloy powder.

[0085] (2) Preparation of piezoelectric white phosphogypsum nanoparticles

[0086] 100 mL of 0.37 M calcium hydroxide solution and 100 mL of 0.13 M magnesium hydroxide solution were mixed and kept at 85 °C for 1 h. Then, 200 mL of 0.5 M phosphoric acid solution was added dropwise at a rate of 12 mL / min. After aging for 20 h, the milky white precipitate was centrifuged at 5000 r / min for 15 min, washed three times, and dried at 100 °C for 12 h to obtain highly crystalline white calcium phosphite (WH) nanoparticles. Finally, the white calcium phosphite (WH) nanoparticles were annealed at 750 °C for 3 h to obtain piezoelectric white calcium phosphite (PWH) with a particle size of 10–100 nm.

[0087] Phase analysis of the above-mentioned white calcium phosphite (WH) and piezoelectric white calcium phosphite (PWH) was performed using X-ray diffraction. The XRD patterns are shown below. Figure 2 As shown, the diffraction peaks of white phosphogypsum and piezoelectric white phosphogypsum are consistent, indicating that they have the same crystal structure.

[0088] The piezoelectric properties of piezoelectric white calcium phosphite (PWH) were tested using piezoelectric force microscopy (PFM), and the test results are as follows: Figure 3 As shown, by Figure 3 Content (a) shows in the piezoelectric response phase hysteresis loop diagram that the phase voltage signal of PWH exhibits a significant 180° phase shift; from Figure 3 As can be seen from the amplitude butterfly loop diagram in content (b), the PWH has a butterfly-shaped hysteresis loop in the voltage range of -10 V to 10 V, indicating that the PWH prepared in this application has a typical piezoelectric response.

[0089] (3) Preparation of ZnMg-PWH particles

[0090] The ZnMg alloy powder prepared in step (1) and the PWH nanoparticles prepared in step (2) were mixed by ultrasonic vibration at 30 kHz for 0.5 h at a mass ratio of 100:1, so that the PWH nanoparticles were attached to the surface of the ZnMg alloy powder by physical adsorption, thus obtaining ZnMg-PWH particles.

[0091] The morphology of ZnMg alloy powder and ZnMg-PWH particles was observed using scanning electron microscopy (SEM), such as... Figure 4 As shown in content (a), the surface of the spherical ZnMg alloy powder is relatively smooth; as Figure 4 As shown in content (b), PWH particles are uniformly covered on the surface of spherical ZnMg alloy powder.

[0092] (4) 3D printed ZnMg-PWH porous scaffold

[0093] A porous ZnMg-PWH scaffold was printed using laser powder bed melting (LPBF) equipment. First, a three-dimensional model of the alloy scaffold was created, and the model was processed using slicing software to generate the laser scanning trajectory. The zinc plate of the substrate was pre-treated with sandblasting and cleaned with anhydrous ethanol to remove surface contaminants. After drying, the substrate was mounted on the forming worktable. Before forming, the substrate was preheated to 100 ℃. Process parameters such as laser power, scanning speed, overlap spacing, and powder layer thickness were set, with the laser power at 160 W, scanning speed at 600 mm / s, overlap spacing at 50 μm, and layer thickness at 30 μm. Then, the ZnMg-PWH particles prepared in step (3) are placed into the powder feeding cylinder of the powder bed laser melting equipment. The powder bed laser melting manufacturing equipment is started, and according to the scanning path and process parameters set above, under the protective atmosphere of high-purity argon with a purity of 99.99%, the ZnMg-PWH particles are melted layer by layer on the forming substrate to obtain a cylindrical ZnMg-PWH porous support with a diameter of 6 mm, a height of 6 mm, a unit size (center-to-center distance between adjacent holes) of 2 mm, and a porosity of 67%. The finished product is shown in the figure. Figure 5 As shown.

[0094] Comparative Example 1

[0095] The method for preparing ZnMg porous scaffolds provided in this application includes the following steps:

[0096] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0097] (2) 3D printing of ZnMg-PWH porous scaffold

[0098] The steps for printing ZnMg porous scaffolds using a laser powder bed melting (LPBF) device are the same as step (4) in Example 1, and a cylindrical ZnMg porous scaffold with a diameter of 6 mm, a height of 6 mm, a unit size (center-to-center distance between adjacent holes) of 2 mm and a porosity of 67% is prepared.

[0099] Simulated dynamic degradation experiments were conducted on the ZnMg-PWH porous scaffold prepared in Example 1 and the ZnMg porous scaffold prepared in Comparative Example 1. Specifically, the porous scaffold samples were immersed in simulated body fluid SBF, and a cyclic dynamic load (20 MPa, 1.25 Hz) was applied to the samples for 15 min. Subsequently, the corrosion products on the surface of the porous scaffold samples were cleaned with a 5% chromic acid solution, and the weight of the porous scaffold samples before and after degradation was weighed and recorded. The test structure of the simulated dynamic degradation experiment is shown below. Figure 6 As shown, under the same load, the degradation degree of the ZnMg-PWH porous scaffold is significantly higher than that of the ZnMg porous scaffold, indicating that PWH can effectively promote the degradation of ZnMg alloy under dynamic load.

[0100] Comparative Example 2

[0101] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0102] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0103] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0104] (3) Preparation of ZnMg-PWH particles

[0105] The ZnMg alloy powder prepared in step (1) and the PWH nanoparticles prepared in step (2) were mixed by ultrasonic vibration at 30 kHz for 0.5 h at a mass ratio of 100:5, so that the PWH nanoparticles were attached to the surface of Zn-0.8Mg alloy powder by physical adsorption, thus obtaining ZnMg-PWH particles.

[0106] (4) 3D printed ZnMg-PWH porous scaffold

[0107] A ZnMg-PWH porous scaffold was printed using a laser powder bed melting (LPBF) device. The laser process parameters used were as follows: laser power of 160 W, scanning speed of 600 mm / s, overlap spacing of 50 μm, and layer thickness of 30 μm. Other steps were the same as step (4) in Example 1.

[0108] Comparative Example 3

[0109] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0110] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0111] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0112] (3) Preparation of ZnMg-PWH particles

[0113] The ZnMg alloy powder prepared in step (1), the PWH nanoparticles prepared in step (2), and the grinding balls were ball-milled at 250 rpm for 30 min in an Ar atmosphere, wherein the mass ratio of ZnMg alloy powder to PWH nanoparticles was 100:1 and the ball-to-material ratio was 8:1.

[0114] (4) 3D printed ZnMg-PWH porous scaffold

[0115] A ZnMg-PWH porous scaffold was printed using a laser powder bed melting (LPBF) device. The laser process parameters used were as follows: laser power of 160 W, scanning speed of 600 mm / s, overlap spacing of 50 μm, and layer thickness of 30 μm. Other steps were the same as step (4) in Example 1.

[0116] Experiments have shown that ZnMg-PWH particles obtained by ball milling cannot be printed using laser powder bed melting technology.

[0117] Comparative Example 4

[0118] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0119] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0120] (2) Preparation of ZnMg-tetragonal barium titanate composite particles

[0121] The ZnMg alloy powder prepared in step (1) and tetragonal barium titanate (T-BTO, particle size 200 nm, purchased from Shanghai Buwei New Materials Co., Ltd.) were mixed by ultrasonic vibration at 30 kHz for 0.5 h at a mass ratio of 100:1, so that the tetragonal barium titanate was physically adsorbed onto the surface of Zn-0.8Mg alloy powder to obtain ZnMg-tetragonal barium titanate composite particles.

[0122] (3) 3D printing of ZnMg-tetragonal barium titanate porous scaffold

[0123] A porous ZnMg-tetragonal barium titanate scaffold was printed using a laser powder bed melting (LPBF) device. The laser process parameters used were as follows: laser power of 160 W, scanning speed of 600 mm / s, overlap spacing of 50 μm, and layer thickness of 30 μm. Other steps were the same as step (4) in Example 1.

[0124] Example 2

[0125] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0126] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0127] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0128] (3) Preparation of ZnMg-PWH particles

[0129] The ZnMg alloy powder prepared in step (1) and the PWH nanoparticles prepared in step (2) were mixed by ultrasonic vibration at 30 kHz for 0.5 h at a mass ratio of 100:0.5, so that the PWH nanoparticles were attached to the surface of Zn-0.8Mg alloy powder by physical adsorption, thus obtaining ZnMg-PWH particles.

[0130] (4) 3D printed ZnMg-PWH porous scaffold

[0131] The steps for printing ZnMg-PWH porous scaffolds using a laser powder bed melting (LPBF) device are the same as step (2) in Example 1.

[0132] Example 3

[0133] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0134] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0135] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0136] (3) Preparation of ZnMg-PWH particles

[0137] The ZnMg alloy powder prepared in step (1) and the PWH nanoparticles prepared in step (2) were mixed by ultrasonic vibration at 30 kHz for 0.5 h at a mass ratio of 100:2, so that the PWH nanoparticles were attached to the surface of Zn-0.8Mg alloy powder by physical adsorption, thus obtaining ZnMg-PWH particles.

[0138] (4) 3D printed ZnMg-PWH porous scaffold

[0139] The steps for printing ZnMg-PWH porous scaffolds using a laser powder bed melting (LPBF) device are the same as step (4) in Example 1.

[0140] Example 4

[0141] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0142] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0143] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0144] (3) The steps for preparing ZnMg-PWH particles are the same as steps (3) in Example 1.

[0145] (4) 3D printed ZnMg-PWH porous scaffold

[0146] A ZnMg-PWH porous scaffold was printed using a laser powder bed melting (LPBF) device. The laser process parameters used were as follows: laser power of 150 W, scanning speed of 700 mm / s, overlap spacing of 55 μm, and layer thickness of 30 μm. Other steps were the same as step (4) in Example 1.

[0147] Example 5

[0148] The method for preparing the personalized intelligent biodegradable implantable device provided in this application includes the following steps:

[0149] (1) The steps for preparing ZnMg alloy powder are the same as steps (1) in Example 1.

[0150] (2) The steps for preparing piezoelectric white calcium phosphate nanoparticles are the same as steps (2) in Example 1.

[0151] (3) The steps for preparing ZnMg-PWH particles are the same as steps (3) in Example 1.

[0152] (4) 3D printed ZnMg-PWH porous scaffold

[0153] A ZnMg-PWH porous scaffold was printed using a laser powder bed melting (LPBF) device. The laser process parameters used were as follows: laser power of 170 W, scanning speed of 800 mm / s, overlap spacing of 60 μm, and layer thickness of 30 μm. Other steps were the same as step (4) in Example 1.

[0154] The compressive strength (yield strength) of the ZnMg-PWH porous scaffolds prepared in Examples 1-5, the ZnMg porous scaffolds prepared in Comparative Example 1 and Comparative Example 2, and the ZnMg-tetragonal barium titanate porous scaffold prepared in Comparative Example 4 were tested. The test results are as follows: Figure 7 The degradation performance of the porous scaffold was tested according to the simulated dynamic degradation experiment described above, and the test results are shown in Table 1.

[0155]

[0156] As shown in Table 1, the implant for critical bone defects (ZnMg-PWH porous scaffold) prepared in this application possesses a suitable porous structure and excellent mechanical properties. It can mimic the trabecular bone structure, promote blood vessel ingrowth and osteoblast differentiation, better facilitate bone remodeling, and provide good support for the critical bone defect portion of the patient. Simultaneously, the aforementioned implant for critical bone defects exhibits sensitive piezoelectric response properties. When the critical bone defect portion begins to be stressed, it can generate a microcurrent in the ZnMg-PWH porous scaffold through stress, promoting the degradation of the ZnMg alloy and releasing Mg. 2+ and Zn 2+ This promotes new bone growth at critical bone defect sites and can adaptively adjust the degradation rate of the ZnMg-PWH porous scaffold based on the stress on the critical bone defect site, achieving intelligent degradation of the ZnMg-PWH porous scaffold. In practical applications, it can be customized and printed according to the shape and size of the patient's critical bone defect, with good shape adaptability.

[0157] Comparative examples show that the three-dimensional porous scaffold prepared in Comparative Example 1, without the addition of piezoelectric white calcium phosphate, exhibits poor piezoelectric response performance. The three-dimensional porous scaffold prepared in Comparative Example 2 has poor mechanical properties. This may be due to excessive piezoelectric white calcium phosphate, causing a large amount of it to fail to adsorb onto the surface of the biodegradable metal material, resulting in agglomeration and affecting the mechanical properties of the printed product. During simulated dynamic degradation experiments, the three-dimensional porous scaffold collapsed, making it impossible to measure its weight loss rate, which is recorded as "-". Comparative Example 3 failed to print a three-dimensional porous scaffold. This may be due to the deformation and breakage of the zinc-magnesium alloy powder during ball milling, leading to poor printability of the composite powder. Additionally, the piezoelectric white calcium phosphate agglomerates significantly during printing, causing stratification with the zinc-magnesium alloy powder, resulting in poor printability. The mechanical properties of the three-dimensional porous scaffold prepared in Comparative Example 4 were poor. The reason for this may be that the tetragonal barium titanate phase detached during the printing process, forming agglomerates of tetragonal barium titanate phase, which affected the fusion of the alloy powder and thus led to a deterioration in the mechanical properties of the three-dimensional porous scaffold. During the simulated dynamic degradation experiment, the three-dimensional porous scaffold collapsed, and its weight loss rate could not be measured, which was recorded as "-".

[0158] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A method for preparing a smart degradable three-dimensional porous scaffold with piezoelectric activity, characterized in that, Includes the following steps: S1. Ultrasonic mixing of piezoelectric white calcium phosphate and biodegradable metal materials yields composite powder; The piezoelectric white calcium phosphate has a particle size of 10 nm to 100 nm; the biodegradable metal material has a melting point of less than 900 °C and a particle size of 15 µm to 53 µm; the mass ratio of the piezoelectric white calcium phosphate to the biodegradable metal material is (0.5 to 2):

100. The ultrasonic mixing frequency is 20KHz~60KHz, and the ultrasonic mixing time is 15min~60min; In the composite powder, piezoelectric calcium phosphate stone is attached to the surface of the biodegradable metal material by physical adsorption. S2. The composite powder is used to prepare the three-dimensional porous scaffold by 3D printing process; The porosity of the three-dimensional porous scaffold is 60%~90%, and the yield strength is 20MPa~80MPa.

2. The production method according to claim 1, characterized by, In step S2, the 3D printing technology is any one of selective laser sintering, selective laser melting, electron beam melting, laser engineered net forming, metal binder jetting, nanoparticle jetting, gel metal printing, and digital light processing.

3. The preparation method according to claim 2, characterized in that, The fabrication of three-dimensional porous scaffolds using selective laser melting technology includes the following steps: The composite powder is placed in the powder feeder of the laser melting system. According to the scanning path and process parameters set by the laser melting system, the composite powder is melted and deposited layer by layer on the forming substrate under a protective atmosphere to prepare the three-dimensional porous scaffold.

4. The production method according to claim 3, characterized by, The process parameters of the laser melting system are: laser power of 150W~180W, scanning speed of 500mm / s~900mm / s, overlap spacing of 40µm~70µm, and powder layer thickness of 30µm~50µm; and / or, The protective atmosphere is selected from at least one of argon, nitrogen, and helium; and / or, The oxygen content in the protective atmosphere is ≤1000ppm; and / or, The forming substrate is a stainless steel plate or a zirconium alloy plate.

5. A smart biodegradable three-dimensional porous scaffold with piezoelectric activity prepared by the preparation method according to any one of claims 1 to 4.

6. An implant for a critical bone defect, characterized in that It includes the three-dimensional porous scaffold as described in claim 5 or the three-dimensional porous scaffold prepared by the preparation method described in any one of claims 1 to 4.

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