Preparation method of cross-scale gradient structure, bone repair material and application method

Abstract

The invention belongs to the technical field of bone repair materials, and discloses a preparation method of a cross-scale gradient structure, a bone repair material and an application method. The preparation method comprises the following steps: preparing a semiconductor biological material into a biological heterojunction suspension, and mixing the biological heterojunction suspension with photocuring hydrogel to form a system; a bone implant base material and a conductive material are respectively used as a positive electrode and a negative electrode to be placed in a system, an electric field is applied to enable the biological heterojunction particles to directionally deposit to form a gradient, the bone repair material with a cross-scale gradient structure is obtained through photo-curing fixation, and a porous scaffold can be preset as required. The material prepared by the method simulates a natural gradient structure of a human skeleton, has composite functions of electric conduction, antibiosis and the like, can give consideration to mechanical support and biological activity, is adaptive to scenes of spine repair, tumor postoperative bone defects and the like, solves the problems that a traditional bone repair material is not matched in structure and single in function, and improves osseointegration efficiency and clinical safety.

Description

Technical Field

[0001] This invention belongs to the field of bone repair materials technology, specifically relating to a method for preparing a multi-scale gradient structure, bone repair materials, and application methods. Background Technology

[0002] Current bone repair materials are mainly developed around the core architecture of substrate support and functional coatings. Common substrates include metal substrates, polymer substrates, and inorganic bioceramic substrates. Metal substrates are mainly titanium alloys and cobalt-chromium alloys, and their surface coatings are mostly prepared by plasma spraying, electrochemical deposition, or magnetron sputtering. For example, a hydroxyapatite coating is deposited on the surface of titanium alloys to improve biocompatibility. Polymer substrates are represented by polyetheretherketone, polycaprolactone, and polylactic acid-glycolic acid copolymers. They are often prepared into porous scaffolds using 3D printing templates or thermoforming processes. Some are combined with inorganic particles such as hydroxyapatite nanoparticles to enhance mechanical properties and bioactivity. Inorganic bioceramic substrates are mainly composed of hydroxyapatite and tricalcium phosphate, prepared by sintering hydrothermal synthesis or sol-gel methods, and can be used alone as a bone defect filling material or in combination with other substrates. In addition, existing bone repair materials also include metal-ceramic composite substrates and polymer-ceramic composite substrates, aiming to balance mechanical properties and bioactivity through material composites.

[0003] Existing bone repair materials have several limitations. First, their structural uniformity does not match the natural structure of human bone. Human bone exhibits a gradient change from a dense layer to a porous layer from the surface to the interior, while the coatings of traditional repair materials are mostly uniform in structure, and the substrate lacks an orderly gradient porosity distribution. This results in low interfacial bonding strength between the material and bone tissue, making them prone to loosening and detachment. Second, the materials have limited functionality and cannot simultaneously meet the requirements of mechanical support, bioactivity, and clinical safety. For example, metal substrates have excellent mechanical properties but low bioactivity, easily triggering long-term interfacial reactions; polymer substrates have good biocompatibility but insufficient mechanical strength, and their degradation rate is difficult to match with the bone repair process; inorganic ceramics have high bioactivity but are brittle and have poor impact resistance. Third, the manufacturing process has defects. High-temperature processes such as plasma spraying can easily destroy the bioactivity of the coating material, electrochemical deposition makes it difficult to precisely control the particle distribution and gradient structure of the coating, and particle agglomeration is prone to occur during 3D printing of composite scaffolds, resulting in poor material performance stability. Fourth, there is insufficient clinical adaptability. Traditional materials are difficult to precisely customize according to the specific shape of bone defects, and the repair process is prone to long bone integration cycle due to insufficient bioactivity, or increased postoperative infection risk due to lack of antibacterial function. Summary of the Invention

[0004] To address the problems existing in the prior art, this invention provides a method for preparing a multi-scale gradient structure, a bone repair material, and an application method. By constructing a charged ion solution under the action of an electric field to form a spatial gradient structure, it is applicable to biomaterials in multiple fields such as bone repair.

[0005] The technical solution adopted in this invention is as follows: In a first aspect, the present invention provides a method for preparing a multi-scale gradient structure, comprising the following steps: Step 100. Disperse at least two semiconductor biomaterials in a solvent, add a surfactant, and then sonicate to obtain a bio-heterojunction suspension; Step 200. Mix the obtained bioheterogeneous suspension with the photocurable hydrogel to form a mixed system; Step 300. Place the bone implant substrate as the negative electrode and the conductive material as the positive electrode in the mixed system, and apply an electric field for treatment; Step 400. The hybrid system after electric field treatment is photocured to obtain a bone implant with a cross-scale gradient structure.

[0006] In conjunction with the first aspect, the present invention provides a first embodiment of the first aspect, wherein the semiconductor biomaterial in step 100 is a biocompatible inorganic semiconductor material or an organic semiconductor material; the inorganic semiconductor material is selected from at least two of MXene, carbon-nitrogen materials, copper sulfide, and zinc oxide, and the organic semiconductor material is selected from biocompatible polymers with conjugated structures.

[0007] In conjunction with the first aspect, the present invention provides a second embodiment of the first aspect, wherein the mixing volume ratio of the bioheterogeneous suspension and the photocurable hydrogel in step 200 is 1:1 to 1:3, the mixing process is carried out by magnetic stirring at a speed of 100-300 rpm for 5-15 minutes.

[0008] In conjunction with the first aspect, the present invention provides a third embodiment of the first aspect, wherein the conductive material in step 300 is a graphite rod, a platinum electrode, or a titanium electrode, and the electrode spacing between the bone implant substrate and the conductive material is controlled to be 1-5 cm.

[0009] In conjunction with the third embodiment of the first aspect, the present invention provides a fourth embodiment of the first aspect, wherein in step 300, the processing time for applying the electric field is 10-30 minutes, and the electric field is a DC electric field or a time-series electric field. When using a time-series electric field, the formation is controlled in three stages: the initial stage applies a voltage of 5-15V for 5-10 minutes, the enhancement stage adjusts the voltage to 20-55V for 3-10 minutes, and the stabilization stage returns to a voltage of 5-15V for 2-5 minutes.

[0010] In conjunction with the first aspect, the present invention provides a fifth embodiment of the first aspect, wherein in step 400, the photocuring uses ultraviolet light with a wavelength of 365-405nm, the irradiation power is 50-100mW / cm², and the photocuring time is 5-15 minutes.

[0011] In conjunction with the first aspect, the present invention provides a sixth embodiment of the first aspect, which further includes the step of adding a porous support to the system before forming the mixed system in step 200; The porous scaffold is made of at least one of polyetheretherketone (PEEK) composite materials, polycaprolactone (PVC) composite materials, and polylactic acid-glycolic acid copolymer (PLCA) composite materials.

[0012] Secondly, the present invention provides a bone repair material formed by any of the above-mentioned methods for preparing a cross-scale gradient structure. The material includes a bone implant substrate and a cross-scale gradient structure formed on the surface of the substrate. The distribution density of the bio-heterogeneous particles in the gradient structure decreases continuously from the surface of the substrate to the interior of the gradient material, and the particle size covers the nanometer to micrometer scale.

[0013] Thirdly, the present invention provides an application method for the use of the bone repair material described above in hard tissue repair.

[0014] In conjunction with the third aspect, the present invention provides a first embodiment of the third aspect, wherein, when applied, the dense side of the gradient structure of the bone repair material faces the surface layer of the bone tissue to be repaired, and the loose side of the gradient structure faces the interior of the bone tissue or is combined with the pore structure of the porous scaffold.

[0015] The beneficial effects of this invention are as follows: (1) The present invention constructs a cross-scale gradient structure by electric field control, the density of which is continuously decreasing from the surface of the substrate to the interior, simulating the natural gradient structure of human bones, so that the bone repair material and the bone tissue to be repaired form a seamless interface contact, significantly improving the interface bonding strength, promoting the orderly growth of bone cells on the coating surface and in the internal pores, accelerating the bone integration process, and solving the problem of weak interface bonding caused by the uniform structure of traditional materials. (2) The present invention uses at least two kinds of semiconductor biomaterials to construct a biological heterostructure, thereby achieving synergistic complementarity of different material functions. It has the electrical signal response capability of semiconductor materials to regulate bone cell proliferation and differentiation, and can also introduce additional functions such as antibacterial and angiogenesis through material combination. At the same time, the biocompatibility of semiconductor materials ensures that there is no obvious rejection reaction after implantation, thus solving the problems of functional limitations and insufficient biological safety of traditional single materials. (3) The preparation process of the present invention combines electric field driven deposition and ultraviolet light curing. The process conditions are mild, avoiding the destruction of the activity of biomaterials by high temperature and high pressure. At the same time, by adjusting the electric field parameters, timing voltage, electrode spacing and the mixing ratio of bio-heterojunction suspension and photocurable hydrogel, the gradient structure and performance can be precisely controlled, ensuring the stability of material performance during batch preparation and reducing material loss and performance fluctuation caused by traditional high temperature preparation process. (4) The present invention can combine the pre-placement of porous scaffolds with 3D printing technology to customize the substrate and scaffold structure according to the specific shape and size of the bone defect to be repaired, so that the repair material can be accurately adapted to the defect site. At the same time, the combination of gradient structure and porous scaffold can take into account both mechanical support and tissue growth space. It can not only meet the mechanical needs of load-bearing parts such as spinal repair, but also provide sufficient cell growth and blood vessel ingrowth channels for bone defect repair after fracture repair and tumor surgery, significantly expanding the clinical application range of the material. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the preparation process in an embodiment of the present invention; Figure 2 These are the surface morphologies of coatings constructed with different voltage intensities in the embodiments of the present invention; Figure 3 The coating constructed by the present invention at 55V voltage and the Ca of hydrothermal synthesis of needle-shaped HA are... 2+ Dissolution diagram; Figure 4 These are X-ray diffraction (XRD) comparison patterns of the coating in Example 2 of this invention and traditional needle-shaped hydroxyapatite; Figure 5 These are X-ray images and three-dimensional modeling images of bone repair in Embodiment 2 of the present invention, where a is a schematic diagram of the first type of bone repair position under X-ray, b is a schematic diagram of the second type of bone repair position in the three-dimensional modeling, and c is a schematic diagram of the second type of bone repair position under X-ray. Figure 6 This is a Micro-CT image of the spatial gradient structure of the bone implant material prepared in the embodiments of the present invention. Detailed Implementation

[0017] The present invention will be further explained below with reference to the accompanying drawings and specific embodiments.

[0018] To make the objectives, technical solutions, and advantages of the embodiments of this application clearer, the technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. The components of the embodiments of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0019] Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of the application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0020] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0021] In the description of this application, it should be noted that the use of terms such as "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer" to indicate orientation or positional relationships is based on the orientation or positional relationships shown in the accompanying drawings, or the orientation or positional relationships commonly used when the product is in use. These terms are used solely for the convenience of describing this application and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application. Furthermore, the use of terms such as "first" and "second" in the description of this application is only used to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0022] Example 1: This embodiment discloses a method for preparing a multi-scale gradient structure, referring to... Figure 1 The specific steps are as follows: 1. Preparation of biological heterojunction suspension At least two biocompatible semiconductor biomaterials are selected, mixed in a mass ratio of 1:1 to 1:3, and added to deionized water. Then, an appropriate amount of biocompatible surfactant is added. The mixture is placed in an ultrasonic instrument and ultrasonically treated for 10-30 minutes at conventional ultrasonic power to obtain a uniformly dispersed suspension of charged semiconductor composite particles, wherein the particle size is distributed in the range of nanometer to micrometer.

[0023] 2. Formation of a mixed system The prepared bio-heterogeneous suspension was mixed with the photocurable hydrogel at a volume ratio of 1:1 to 1:3. The mixture was stirred with a magnetic stirrer at a speed of 100-300 rpm for 5-15 minutes to ensure that the bio-heterogeneous particles were uniformly dispersed in the photocurable hydrogel and to form a stable mixture system.

[0024] 3. Electric field treatment to construct gradient The bone implant substrate (as the negative electrode) and the conductive material (as the positive electrode) are placed parallel to each other in the above-mentioned mixed system. The distance between the two electrodes is controlled to be 1-5 cm. A DC power supply is connected and a voltage in the range of 5-55V is applied. The electric field is maintained for 10-30 minutes to allow the biological heterojunction particles to be directionally deposited on the surface and surrounding area of ​​the bone implant substrate, forming a preliminary gradient distribution.

[0025] 4. Light-curing fixing structure Remove the bone implant substrate and the mixed system after electric field treatment, and irradiate the mixed system with ultraviolet light with a wavelength of 365-405nm. The irradiation power is set to 50-100mW / cm² and the irradiation is continued for 5-15 minutes. After the photocurable hydrogel is completely cross-linked and cured, rinse the surface of the substrate with deionized water to obtain a bone repair material with a cross-scale gradient structure on the surface.

[0026] Semiconductor properties are key. During bone repair, cells transmit growth instructions via weak electrical signals (e.g., osteoblast proliferation depends on electrical stimulation). Semiconductor materials can receive and amplify these signals, directly promoting bone cell attachment and growth. While a single material has limited functionality, combining two materials can simultaneously possess multiple functions such as conductivity, antibacterial properties, and cell proliferation promotion, meeting the diverse needs of human tissue repair. The materials selected in this embodiment, such as MXene, ZnO, and CN, have all undergone biosafety verification and will not cause rejection or toxicity after implantation, ensuring safety for clinical application.

[0027] Example 2: Preferably, the preparation is carried out based on the method of Example 1 above, with the application direction of high-strength bone repair material for spinal repair.

[0028] 1. Preparation of functionalized semiconductor composite particle suspension MXene and zinc oxide were selected as semiconductor biomaterials and mixed at a mass ratio of 2:1. The mixture was then added to deionized water, and sodium dodecyl sulfate (0.5 wt%) was added as a surfactant. The mixture was placed in an ultrasonic instrument and ultrasonically treated at 200 W for 25 minutes to obtain a negatively charged biological heterojunction suspension. The MXene particles were 100 nm in size, and the zinc oxide particles were 500 nm in size. The suspension exhibited both high conductivity and antibacterial properties.

[0029] 2. Mixed photocurable hydrogel with pre-placed porous scaffold Methacrylated gelatin was selected as the photocurable hydrogel. The bio-heterogeneous suspension was mixed with the photocurable hydrogel at a volume ratio of 1:1.5, and stirred at 250 rpm for 12 minutes using a magnetic stirrer. A polyetheretherketone (PEEK)-based porous scaffold was fabricated using 3D printing. The 3D-printed PEEK-based porous scaffold was then subjected to magnetron sputtering titanium deposition. The process is as follows: A 3D-printed polyetheretherketone (PEEK) porous scaffold was placed in a magnetron sputtering apparatus, using a pure titanium target as the sputtering source. The sputtering power was set to 150-200W and the vacuum level to no more than 5×10⁻⁶. -3 Pa, argon flow rate 20-30 sccm, sputter a 50 nm titanium thin film on the surface of the support to form a uniform conductive layer, and then vacuum cool to room temperature for later use. The polyether ether ketone-based porous scaffold was then completely immersed in the mixed system. The scaffold had a porosity of 60% and a pore size of 200-300 micrometers. It was then left to stand for 5 minutes to allow the mixture to fully penetrate the scaffold pores.

[0030] 3. Precise gradient control of time-series electric field Using a polyetheretherketone (PEEK)-based porous scaffold treated with titanium thin film sputtering as the negative electrode and a platinum electrode as the positive electrode, the distance between the two electrodes was controlled to be 2 cm. A time-series electric field was applied: in the initial stage, a voltage of 10V was applied for 8 minutes to allow particles to initially adhere to the surface of the scaffold and the pore entrance; in the strengthening stage, the voltage was adjusted to 45V for 6 minutes to promote dense particle deposition on the outer surface of the scaffold and the load-bearing area; in the stabilizing stage, the voltage was adjusted back to 10V for 4 minutes to allow a small number of particles to penetrate into the pores inside the scaffold.

[0031] 4. Photocuring and post-treatment Irradiation with 365nm ultraviolet light for 12 minutes was used to allow the hydrogel to fully solidify. The scaffold was then immersed in sterile saline solution for 2 hours to remove residual surfactants, resulting in a bone repair material suitable for spinal repair. This material forms a dense layer with a particle packing density ≥80% on the outer surface of the scaffold, and a loose layer with a particle packing density ≤30% in the internal porous region, balancing mechanical strength and osseointegration capacity.

[0032] Example 3: Preferably, based on the method of Example 1 above, the material is prepared with the application of a biodegradable repair material for bone defects after tumor surgery.

[0033] 1. Preparation of biocompatible semiconductor composite particle suspension Carbon-nitrogen materials and polycaprolactone were mixed at a mass ratio of 1:3 and added to deionized water. Tween-80 at a concentration of 0.3 wt% was added as a surfactant. The mixture was placed in an ultrasonic instrument and ultrasonically treated at 150 W for 30 minutes to obtain a uniformly dispersed bio-heterogeneous suspension. Polycaprolactone ensured the biodegradability of the material, while carbon-nitrogen materials enhanced bioactivity.

[0034] 2. Mixing and bracket pre-setting The bio-heterogeneous suspension was mixed with methacrylic anhydride-modified hyaluronic acid photocurable hydrogel at a volume ratio of 1:2.5. The mixture was stirred at 150 rpm for 8 minutes using a magnetic stirrer. Then, the 3D-printed polycaprolactone-based porous scaffold was placed into the mixture and allowed to stand for 6 minutes to ensure that the mixture completely filled the scaffold pores.

[0035] 3. Constructing a gradient in a DC electric field Using a magnetron sputtered polycaprolactone-based porous scaffold as the negative electrode and a titanium electrode as the positive electrode, the distance between the two electrodes was controlled to be 4 cm. A DC power supply was connected and a voltage of 25V was applied. The electric field was maintained for 25 minutes, which caused the bio-heterogeneous nodular particles to be densely deposited in the area of ​​the scaffold near the bone defect surface and to form a loose layer on the side away from the defect, thus matching the repair needs of bone defects after tumor surgery.

[0036] 4. Light curing and sterilization The hydrogel was irradiated with 405nm ultraviolet light (60mW / cm²) for 15 minutes until it was completely cured. Then, the material was sterilized in an ethylene oxide sterilizer to obtain a biodegradable bone repair material. This material exhibits a degradation rate that matches the bone repair cycle. The dense layer can quickly bond to the bone defect surface, while the porous layer provides ample space for new bone tissue growth, reducing the risk of secondary damage after tumor surgery.

[0037] To verify the preparation method and material properties in the above embodiments, this embodiment provides the following performance tests and effect verification.

[0038] (1) Gradient structure characterization Experimental methods Examples 2 (45V sequential electric field), 3 (25V DC electric field), and the control group (samples prepared under 85V DC electric field) were used. The surface morphology of the materials was observed using a scanning electron microscope, and the internal structure of the materials was scanned using Micro-CT to analyze the gradient change of particle packing density.

[0039] Experimental results (refer to) Figure 2 and Figure 6 ) Example 2 Sample: The particle packing density on the outer surface of the scaffold is 82%, and the particle packing density in the internal pore region is 28%. Micro-CT scan shows a continuous density gradient from the surface to the interior, which is highly consistent with the surface-interior structure of the human tibia.

[0040] Example 3 sample: The particle packing density on the defect side is 75%, and the packing density on the side away from the defect is 25%. Micro-CT shows that the particles in the pores are dense on the outside and sparse on the inside, which is suitable for the surface bonding and internal growth requirements of bone defects after tumor surgery.

[0041] Control group: SEM showed excessive aggregation of surface particles, with cracks 5-10 micrometers in diameter. Figure 2 Micro-CT showed no significant gradient change, and particles blocked the pores (porosity dropped to 8%), making it unable to adapt to bone cell growth.

[0042] in conclusion In this embodiment, a dense-sparse continuous gradient structure can be precisely constructed by adjusting the voltage from 5 to 55V. The gradient is destroyed by an excessively high voltage of 85V, which proves the rationality of the process parameters in this embodiment. Furthermore, the gradient structure is highly biomimetic to the human skeleton, solving the mismatch problem of traditional uniform coating structures.

[0043] (2) Bioactivity verification Experimental methods Before the experiment, X-ray diffraction was used to analyze the phase composition of the sample in Example 2. The results showed that the sample contained characteristic diffraction peaks of hydroxyapatite (2θ=25.9°, 31.8°) and characteristic peaks of zinc oxide (ZnO) (2θ=31.8°, 34.5°), confirming the formation of the composite phase structure.

[0044] Then, the sample from Example 2 (45V time-series electric field) was taken, cut into 1cm×1cm specimens, and placed in simulated body fluid at 37℃. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to detect Ca²⁺ levels at 1 day, 3 days, 7 days, and 14 days. + Dissolution concentration; at the same time, a traditional titanium alloy HA material group was set up as a control, and the proliferation rate of osteoblasts on the sample surface was detected by MTT method.

[0045] Experimental results (refer to) Figure 3 (The data corresponding to the part) Ion dissolution characteristics: Ca 2+ It synergistically dissolves with Zn²⁺, with Ca²⁺ dissolving concentrations of 9.2±1.5 mg / L on day 1, 5.1±0.8 mg / L on day 3, 3.3±0.5 mg / L on day 7, and 1.8±0.3 mg / L on day 14; and Zn²⁺ dissolving concentrations of 1.2±0.2 mg / L on day 1, maintaining at 0.5-0.8 mg / L from day 3 to day 14.

[0046] The high dissolution in the initial stage originates from the dissolution of amorphous phase on the surface of gradient materials, providing initial mineralized ions for bone repair. Subsequent steady-state dissolution supports continuous mineralization activity, which is highly compatible with the characteristics of the initial activation-mid mineralization-late stability process of human bone repair. Traditional HA material group: The Ca²⁺ dissolution concentration was 15.3±2.1 mg / L after 1 day. Excessive dissolution can easily lead to local tissue calcification. After 7 days, it dropped to 0.5±0.1 mg / L, while insufficient dissolution could not support continuous mineralization, proving that the dissolution stability was significantly worse than that of the sample in Example 2 of this invention. Cell proliferation rate: In Example 2, the osteoblast proliferation rate after 7 days of culture was 185%, compared to 100% in the blank group and 132% in the traditional HA material group. This demonstrates that the gradient material obtained in this example can significantly promote osteoblast growth. (Refer to...) Figure 5 It can be known that...

[0047] in conclusion The gradient material Ca² in this embodiment + Its dissolution characteristics and bioactivity are superior to traditional coatings, which can effectively promote osseointegration and support the beneficial effect of accelerating the bone repair process.

[0048] (3) Mechanical property testing Experimental methods Examples 2 (spinal repair material), 3 (biodegradable material), and a traditional polyetheretherketone (PEEK) scaffold assembly were tested using a universal testing machine. Compressive strength, according to GB / T1041-2008 standard; Interface bonding strength: The tensile bond strength between the gradient material and the substrate was tested according to GB / T6396-2008 using a universal testing machine. The sample size was 10mm×10mm×5mm, the crosshead speed was 0.5mm / min, and the ambient temperature was 25℃ and the humidity was 50%RH.

[0049] Experimental results Example 2: The compressive strength is 92 MPa, which meets the load-bearing requirements of the spine. The tensile bond strength of the gradient material-substrate is 15 ± 2 MPa. The bond strength of the traditional PEEK surface HA material group is 6 ± 1 MPa. The bond strength of the sample of this invention is improved by about 150%. Observation shows that there are obvious hydrogel-substrate interface fusion characteristics on the fracture surface, and no peeling phenomenon. Example 3: After 3 months of degradation, the compressive strength still remains at 45 MPa, which is 30 MPa higher than the strength of human cancellous bone. The gradient material-substrate bonding strength is 12 ± 1.5 MPa, which can effectively avoid the risk of material loosening after tumor surgery.

[0050] in conclusion The material of this invention balances mechanical strength and interfacial bonding, solving the problems of insufficient strength and poor adhesion of traditional polymer scaffolds and metal coatings.

[0051] (4) Antibacterial and degradation performance test Antibacterial properties Experimental method: Staphylococcus aureus was used as the test strain. The samples were cut into 20×20×2mm specimens, aseptically treated, and placed in 96-well plates. 10 wells were inoculated. 5100 μL of CFU / mL bacterial culture was incubated at 37℃ in a 5% CO2 incubator for 24 hours. After incubation, the viable bacteria were washed and counted using the plate count method. A PEEK scaffold without antibacterial coating was set up as a control group. The antibacterial rate was calculated using the formula: Antibacterial rate = (Viable bacteria count in control group - Viable bacteria count in experimental group) / Viable bacteria count in control group × 100%. Simultaneously, two parallel experiments were set up: one with 365nm ultraviolet light irradiation for 30 min and the other in the dark environment. result: 365nm ultraviolet light irradiation group: antibacterial activity ≥3.0 LogReduction, that is, more than 99.9% of live bacteria were killed, while the control group had no obvious antibacterial effect; Dark environment group: antibacterial activity ≥1.5 LogReduction, meaning that more than 96.8% of live bacteria were killed.

[0052] The results show that the gradient material of the present invention has a significant antibacterial effect under photoactivated conditions, which can effectively reduce the risk of infection after spinal implantation.

[0053] Degradation performance Experimental methods: The samples were placed in simulated body fluid at 37℃, and the mass loss rate was calculated by periodic weighing. The molecular weight changes of polycaprolactone and MA-HA were detected by GPC gel permeation chromatography. At the same time, the pH value of the degradation solution was measured periodically to analyze the impact of degradation products on the microenvironment. result: Degradation performance: 3-month mass loss rate 18±2%, 6-month mass loss rate 45±3%, 12-month mass loss rate 78±4%; During the degradation period of 3-12 months, the compressive strength retention rate of the material is >60%, which can meet the mechanical support needs of tumor surgery for 6-12 months.

[0054] GPC testing showed that the molecular weights of PCL and MA-HA gradually decreased without any sudden drop; the pH value of the degradation solution remained between 7.2 and 7.4, with no accumulation of acidic small molecules, thus avoiding local inflammatory reactions. The degradation cycle was synchronized with the bone repair cycle, eliminating the need for a second surgery to remove the bone.

[0055] (5) Lattice doping and preferred orientation analysis Experimental methods Approximately 50 mg of powder scraped from the surface of the gradient structure in Example 2 was compared with pure HA powder in the comparative example using XRD: Sample preparation: Powder compression method, pressure 5 MPa, hold for 30 seconds Testing equipment: X-ray diffractometer, CuKα rays (λ=1.5406Å) Test parameters: tube voltage 40kV, tube current 30mA, scan speed 2° / min, step size 0.01° Data analysis: Peak position fitting and grain size calculation were performed using Jade 6.0 software. Reference Figure 4 As shown in the diagram, the gradient material of this invention (red line) differs significantly from pure HA (black line) in three key indicators: Evidence of lattice distortion The gradient material of this invention exhibits a strong diffraction peak at 2θ = 29.8°, which is 0.9° positively shifted from the standard HA(210) peak (28.9°), corresponding to a reduction in interplanar spacing from d = 0.309 nm to d = 0.304 nm; Rietveld's refined analysis revealed that the shift originated from Zn²⁺ (ionic radius 0.074 nm) partially replacing Ca²⁺ (ionic radius 0.100 nm) in the HA lattice, forming Zn. x Ca 10 ₋ x (PO4)6(OH)2 solid solution, doping amount x=0.15-0.20 (verified by EDS quantitative analysis).

[0056] Optimism Index Calculate the intensity ratio of the diffraction peaks of the (210) and (002) crystal planes: I 210 / I 002 =0.78; The ratio of the pure HA control group was only 0.35, which proves that the present invention induces HA crystals to grow perpendicular to the substrate surface along the (210) plane under electric field drive. This orientation is consistent with the direction of physiological load on bone, which increases the elastic modulus of the gradient material to 18GPa (nanoindentation test), which is closer to natural bone (15-25GPa), and optimizes the interface stress matching degree.

[0057] Quantitative analysis of crystallinity The gradient material of this invention has a peak half-width at half-maximum (FWHM) of 0.19° and an average grain size of D of 42 nm calculated by Scherrer's formula. The pure HA control group had an FWHM of 0.42° and a D of 19 nm. Its low crystallinity resulted in a decrease in Ca²⁺ dissolution to 0.08 mg / L after 14 days, indicating insufficient mineralization activity. The high crystallinity of this invention ensures a steady-state dissolution of Ca²⁺ at 0.25-0.30 mg / L for 14 days, meeting the needs of the entire bone repair cycle.

[0058] This invention is not limited to the optional embodiments described above, and anyone can derive other various forms of products based on the inspiration of this invention. The specific embodiments described above should not be construed as limiting the scope of protection of this invention; the scope of protection of this invention should be determined by the claims, and the specification can be used to interpret the claims.

Claims

1. A method for preparing a cross-scale gradient structure, characterized by, The method comprises the following steps: Step 100. Dispersing at least two semiconductor biomaterials in a solvent, and then performing ultrasonic treatment after adding a surfactant to obtain a bioheterojunction suspension; Step 200. Mixing the obtained bioheterojunction suspension with a photocured hydrogel to form a mixed system; Step 300. Placing a bone implant base as a negative electrode and a conductive material as a positive electrode in the mixed system, and applying an electric field for treatment; Step 400. Photocuring the mixed system after the electric field treatment to obtain a bone implant with a cross-scale gradient structure.

2. The method of claim 1, wherein the method further comprises: In the step 100, the semiconductor biomaterials are biocompatible inorganic semiconductor materials or organic semiconductor materials; the inorganic semiconductor materials are selected from at least two of MXene, carbon-nitrogen material, copper sulfide and zinc oxide, and the organic semiconductor materials are selected from biocompatible polymers with a conjugated structure.

3. The method of claim 1, wherein the method further comprises: In the step 200, the volume ratio of the bioheterojunction suspension to the photocured hydrogel is 1:1-1:3, the mixing process adopts magnetic stirring, the stirring rate is 100-300 rpm, and the stirring time is 5-15 minutes.

4. The method of claim 1, wherein the method further comprises: In the step 300, the conductive material is a graphite rod, a platinum electrode or a titanium electrode, and the electrode spacing between the bone implant base and the conductive material is controlled to be 1-5 cm.

5. The method of claim 4, wherein the method further comprises: In the step 300, the treatment time of the applied electric field is 10-30 minutes, and the electric field is a direct current electric field or a time sequence electric field. When the time sequence electric field is used, the three stages of an initial stage of 5-15 V for 5-10 minutes, a strengthening stage of 20-55 V for 3-10 minutes, and a stable stage of 5-15 V for 2-5 minutes are sequentially controlled.

6. The method of claim 1, wherein the method further comprises: In the step 400, the photocuring adopts ultraviolet light with a wavelength of 365-405 nm, an irradiation power of 50-100 mW / cm², and a photocuring time of 5-15 minutes.

7. The method of claim 1, wherein the method further comprises: Further comprising a step of adding a porous scaffold to the system before forming the mixed system in the step 200; The material of the porous scaffold is selected from at least one of polyether ether ketone-based composite material, polycaprolactone-based composite material and polylactic acid-glycolic acid copolymer-based composite material.

8. A bone repair material, characterized by, The material formed by the method for preparing a cross-scale gradient structure according to any one of claims 1-7 comprises a bone implant base and a cross-scale gradient structure formed on the surface of the base; the distribution density of the bioheterojunction particles in the gradient structure shows a continuous decreasing trend from the surface of the base to the interior of the gradient material, and the particle size covers the nanoscale to the microscale.

9. An application method characterized by comprising: The application of the bone repair material according to claim 8 in hard tissue repair.

10. The method of claim 9, wherein the composition is applied to the skin of the user. In the application, the dense side of the gradient structure of the bone repair material faces the surface layer of the bone tissue to be repaired, and the loose side of the gradient structure faces the interior of the bone tissue or is combined with the pore structure of the porous scaffold.

Images