CN113143550B - Fusion device with multi-layer bionic active fusion function and preparation method thereof - Google Patents

Abstract

The invention discloses a fusion device with a multi-level bionic active fusion function and a preparation method thereof, wherein the fusion device combines a reverse engineering technology and a 3D printing technology, a macroscopic appearance and a double-scale bone-like porous structure of the fusion device are customized by utilizing a laser selective fusion technology, a nano-scale bioactive coating of the fusion device is constructed by utilizing alkaline heating, sintering and electrodeposition technologies, and the fusion device with the multi-level bionic active fusion function, which is constructed by compounding the millimeter-scale macroscopic appearance, the micro-scale bone-like porous, the micro-nano-scale secondary porous and the nano-scale bioactive coating, is obtained. Can effectively solve the problems of single configuration on the macro scale, poor matching effect, unsatisfied use requirement on the aperture scale on the micro scale, easy falling off and sinking and no biological function of active fusion of bone tissues existing in the prior fusion device.

Description

Fusion device with multi-layer bionic active fusion function and preparation method thereof

Technical Field

The invention relates to the technical field of biomedical materials, in particular to a multi-layer bionic active fusion device and a preparation method thereof.

Background

The spine is the axial skeleton of the human body and is the pillar of the body. The spine has the important functions of supporting the human body, maintaining stability, conducting load, sports, protecting spinal cord and the like, and is one of the sources of human health. However, in middle-aged and elderly people in China, 90% of the people suffering from spinal diseases and more than 40% of the people under 40 years old suffer from spinal diseases with different degrees, and due to social development and popularization of remote offices, the working intensity of middle-aged and young people is increased, the working time is prolonged, the low-head group and the sedentary group are generated, and the incidence rate of spinal diseases rises year by year and is in a younger trend.

Spinal fusion is one of the most widely used surgical techniques for spinal surgery, and is mainly promoted by establishing immediate stabilization of the spinal column and osteogenesis, osteoinduction and bone conduction actions of implants, and has been recognized as having better curative effects on such diseases. In the process of selecting implant materials, because of few sources of autologous bone, increased trauma of patients and irregular appearance, the allogenic bone can generate immune rejection reaction with hosts, at present, the realization of intervertebral fusion by using an intervertebral fusion device has become a main means for treating spinal diseases, the appearance of the implant materials can be designed, the sources are wide, no secondary damage exists, the height of intervertebral space can be maintained, the support of a middle column before recovery is realized, the capacity of intervertebral foramen is increased, nerve root compression is relieved, and the intervertebral space collapse and the formation of false joints are prevented.

The titanium alloy interbody fusion cage which is mature in the market depends on import, is high in price and has various problems. On a macroscopic scale, the configuration is limited, accurate matching with the most common patients cannot be realized, the method is more fashionable when the method is used for repairing the grade of difficult and complicated diseases, the matching effect is poor, and the treatment effect is also poor; in microscopic scale, only a simple sub-millimeter porous structure design is realized, innovation is not performed at the level of tens of micrometers, and no bionic is performed, so that the operation effect is poor; on a microscopic scale, biological performance is not improved, and dynamic regulation and control processes such as active materials and the like are lacked, so that bone fusion is slow, postoperative recovery is difficult, and survival quality of patients is low. These problems increase the physical, psychological and economic burden of the patient.

Disclosure of Invention

Aiming at the defects, the invention aims to provide a fusion device with a multi-layer bionic active fusion function and a preparation method thereof. Can effectively solve the problems of single configuration on the macro scale, poor matching effect, unsatisfied use requirement on the aperture scale on the micro scale, easy falling off and sinking and no biological function of active fusion of bone tissues existing in the prior fusion device.

In order to achieve the above purpose, the invention adopts the following technical scheme:

the invention provides a fusion device with a multi-layer bionic active fusion function, which comprises a four-layer bionic structure, wherein the first-layer bionic structure is a macroscopic appearance structure of the fusion device, the second-layer bionic structure is a structural unit body of the first-layer bionic structure, the structural unit body is a macroscopic porous structure, the third-layer bionic structure is a morphology regulation structure of the second-layer bionic structure, the morphology regulation structure is a micro-nano topological structure, and the fourth-layer bionic structure is a biological activation coating on the surface of the third-layer bionic structure.

Further, the macro-topography comprises a bone grafting region and a caudal fixation interface.

Further, the bone grafting area is provided with an upper oval opening and a lower oval opening.

Further, the front portion of the macro-profile structure is narrower than the rear portion.

Further, the structural unit bodies are connected in a space array arrangement mode, specifically, the structural unit bodies are respectively arranged in three directions of a space X axis, a space Y axis and a space Z axis, and the unit bodies are tangent to each other.

Further, the scale of the first-level biomimetic structure is a millimeter scale.

Further, the second-level bionic structure has a micrometer scale, a porosity of 70% -90% and a pore diameter of 600-900 μm.

Further, the third-level bionic structure has a micro-nano scale and a pore diameter of 20-200 μm.

Further, the fourth-level bionic structure has a nano-scale and a pore diameter of 10-1000nm.

Further, the structural unit body is a diamond structural unit body, and specifically a diamond cubic crystal structure.

Further, the micro-nano topological structure is a regularly arranged porous structure or a randomly distributed topological structure.

Further, the topology structure is a star structure, a ring structure, a tree structure or a net structure.

Further, the bioactive coating is a sodium titanate crystal layer or a hydroxyapatite coating.

Further, the raw material of the fusion device is titanium alloy.

The first-level bionic structure is a macroscopic appearance structure of the fusion device, the configuration of the first-level bionic structure is not particularly limited, modeling can be carried out according to the geometric characteristics of an applicable individual, and the macroscopic appearance structure of the fusion device can be manufactured in a personalized way, so that high-precision matching with adjacent upper and lower vertebral bodies of the applicable individual is realized; the second-level bionic structure of the fusion device is a macroscopic bionic mechanical porous structure constructed on a micrometer-scale bone-like trabecular structure, so that the mechanical performance is bionic, and further precision matching of the fusion device and an applicable individual is realized; the third-level bionic structure of the fusion device has a micro-topological morphology structure with the aperture of 20-200 mu m on a micro-nano scale, so that a structure with higher precision and better bone conduction capability are realized; the fourth-level bionic structure of the fusion device has a biological activation coating with the aperture of 10-1000nm on the nanometer scale, so that the biological functions of actively inducing bone tissue regeneration and promoting active fusion between vertebrae are realized.

The invention also provides a preparation method of the fusion device with the multi-layer bionic active fusion function, which comprises the following steps:

step 1, constructing a fusion device model with a first-level bionic structure and a second-level bionic structure;

step 2, constructing a third-level bionic structure of the fusion device according to the fusion device model obtained in the step 1, and obtaining the fusion device with the third-level bionic structure;

and 3, biologically activating the fusion device with the three-level bionic structure obtained in the step 2, and constructing a fourth-level bionic structure of the fusion device to obtain the fusion device with the multi-level bionic active fusion function.

Further, the specific process of the step 1 is as follows:

step 1.1, reconstructing a focus model;

step 1.2, constructing a first-level bionic structure of the fusion device according to the focus model obtained in the step 1.1;

and 1.3, simulating the real stress of the upper cone and the lower cone of the implantation area of the fusion device through finite element analysis and algorithm calculation, and constructing a second-level bionic structure of the fusion device.

Further, the specific process of reconstructing the focus model in step 1.1 is as follows: patient-individuated lesion CT data is acquired, and a lesion model is identified and reconstructed using MIMICS software.

Further, the specific process of the step 2 is as follows: and (3) introducing the fusion device model with the first-level bionic structure and the second-level bionic structure obtained in the step (1) into a 3D printer, and constructing a third-level bionic structure of the fusion device by a laser selective fusion technology and controlling and adjusting the technological parameters of the fusion device model to obtain the fusion device with the third-level bionic structure.

Further, the third-level bionic structure of the fusion cage constructed in the step 2 comprises the following steps:

step 2.1, regulating and setting process parameters of a 3D printer; comprises laser power of 10-100W, scanning speed of 200-2000 mm/s, printing interval of 0.1-0.5 mm and powder spreading layer thickness of 25-100 mu m; the micro-nano topological structure with finer precision than the highest printable model can be a regularly arranged porous structure or a randomly distributed topological structure; the minimum dimension of the structure can reach 20 mu m, and is 100 mu m lower than the minimum printable morphology dimension limited by the laser spot diameter;

step 2.2, slicing the model with the parameter ratio set in the step 2.1, and printing by using a laser selective area melting technology; in the printing process, the laser accumulates a target model layer by layer according to a set path, and a printed sample has a micro-nano morphology structure with smaller dimension, so that the third-level bionic structure is established.

Further, the biological activation process in the step 3 is as follows:

step 3.1, placing the fusion device in an alkaline solution, and reacting for 1-3 hours at the temperature of 55-75 ℃ to generate sodium titanate hydrogel;

and 3.2, drying the sodium titanate hydrogel obtained in the step 3.1, performing sintering heat treatment, preserving heat at 500-700 ℃ for 1-3 hours, and cooling along with a furnace at a heating rate of 4-7 ℃/min, and dehydrating the hydrogel to obtain sodium titanate crystals, thereby obtaining a sodium titanate crystal layer.

Further, the sodium titanate crystal layer in the step 3.2 can be converted into a hydroxyapatite coating on the surface of the fusion device by an electrochemical deposition method; specific working parameters of the electrochemical deposition method are as follows: (1) The sample, the platinum plate and the saturated calomel electrode are respectively used as a cathode, an anode and a reference electrode; (2) the temperature of the electrolyte is 75-90 ℃; (3) CaCl (CaCl) ₂ ·6H ₂ O、NH ₄ H ₂ PO ₄ The molar ratio of NaCl to NaCl is 20-30:10-20:1-3; (4) washing with clear water and drying at room temperature.

Further, caCl ₂ ·6H ₂ O、NH ₄ H ₂ PO ₄ And NaCl at a molar ratio of 25:15:1.5, the temperature of the electrolyte was 85 ℃.

The invention has the following advantages:

1. the invention provides a fusion device with a multi-layer bionic active fusion function, which is compositely constructed by a millimeter-scale macroscopic appearance, a micrometer-scale bone-like porous, a micro-nano-scale secondary porous, a nanometer-scale sodium titanate crystalline layer or a hydroxyapatite coating; the appearance personalized design and the bone-like porous structure construction are realized on a macroscopic scale, the micro-nano topological structure and the surface biological activity nano coating are realized on a microscopic scale, the appearance characteristics, the mechanical property and the biological activity of the fusion device are obviously optimized, the bone regeneration can be actively induced, and the bone active fusion function is realized.

2. The invention provides a preparation method of a multi-layer bionic active fusion device, which aims at an individual lesion information construction model of each patient, and adopts a metal 3D printing advanced technology to carry out individual customization of products, so that the precision is high, the quality is excellent, the manufacturing cost is reduced by 20% -40%, the production period is shortened by 80%, and the individual adaptation rate is more than 95%.

3. The invention provides a preparation method of a multi-layer bionic active fusion device, which is characterized in that stress environments of a bionic natural spinal system are analyzed through finite elements, the intervertebral fusion device with different mechanical requirements is constructed by utilizing the mechanical differences of porous structures, parameters such as unit body configuration, rod diameter, aperture, porosity and the like are regulated, stress shielding is reduced, and a space is reserved for growth of cell colonies, blood vessels and new bone tissues.

4. The invention provides a preparation method of a multi-layer bionic active fusion device, which breaks through the highest printable precision of a machine by combining original technological parameters, can prepare a micro-topology structure of <100 micrometers, is close to the size of osteoblasts, is beneficial to cell proliferation and adhesion, and accelerates new bone ingrowth.

5. The invention provides a preparation method of a multi-layer bionic active fusion device, which constructs a bioactive coating on the surface of a titanium alloy through alkali heat treatment and electrochemical deposition, realizes that the interfacial bioactivity of the titanium alloy is free from organic matters, and realizes organic osseous combination of organisms and implants, thereby remarkably improving the bone conductivity.

Drawings

Fig. 1 is a physical outline view and a multi-level SEM view of the fusion cage with multi-level bionic active fusion function obtained in example 1; wherein fig. 1 (a) is a first-level millimeter-scale macroscopic structure object diagram of the fusion device in the embodiment; FIG. 1 (b) is a schematic SEM topographic map of a second-level microscale macrostructure and a third-level microscale surface topology of the cage of the example, resulting in a macrostructure of diamond structural unit combinations with a unit cell width (i.e., rod diameter) of 400 μm, a pore size of 660 μm, and a porosity of 61.3%; FIG. 1 (c) is an SEM topography of the third level micro-nano scale surface topology of the cage in the example, resulting in a regularly arranged porous structure with micro-nano scale topography, specifically 70-85 μm in size; FIG. 1 (d) is an SEM topography of the fourth level nanoscale surface topology of the cage of the example, resulting in 10-100nm size nanoscale sodium titanate crystals on the surface of the titanium alloy.

Fig. 2 is a second and third level SEM images of the fusion cage with the multi-level biomimetic active fusion function obtained in example 4. Fig. 2 (a) is a SEM topographic map of a second-level microscale macroscopic porous structure of the cage and a third-level micro-nano-scale surface topology of the cage according to the embodiment, and the parameters of the second-level are the same as those of embodiment 1. Fig. 2 (b) is an SEM topography of a third-level micro-nano-scale surface topology of the fusion device in the embodiment, and the obtained topography of micro-nano scale is specifically a topology of <100 μm scale irregular arrangement.

Fig. 3 is a micrometer-scale SEM image of a cage having only first and second-level biomimetic structures obtained in comparative example 2, the cage surface being free of a third-level micro-nano-scale structured micro-topology.

Fig. 4 is a nanoscale SEM image of a cage having only first, second, and third hierarchical biomimetic structures obtained in comparative example 3, the cage surface being free of a fourth hierarchical nanoscale sodium titanate crystalline topology and its capillary micropores.

FIG. 5 is a schematic diagram of the structure and relationship of the multiple layers of the fusion device with the bionic active fusion function; 1, a first-level bionic structure; 1-1, a bone grafting area; 1-2, a tail fixing interface; 2. a second hierarchical biomimetic structure; 3. a third level biomimetic structure; 4. fourth level biomimetic structure.

Fig. 6 is a physical outline view and a multi-level SEM view of the fusion cage with multi-level bionic active fusion function obtained in example 8 of the present invention.

Detailed Description

The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the particular embodiments described herein are illustrative only and are not intended to limit the invention, i.e., the embodiments described are merely some, but not all, of the embodiments of the invention. The components of the embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.

Thus, the following detailed description of the embodiments of the invention, as presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be made by a person skilled in the art without making any inventive effort, are intended to be within the scope of the present invention.

It is noted that relational terms such as "first" and "second", and the like, are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.

Example 1

The invention relates to a fusion device with a multi-layer bionic active fusion function, which comprises a four-layer bionic structure, wherein the first-layer bionic structure is a macroscopic appearance structure of the fusion device, the macroscopic appearance structure comprises a bone grafting area and a tail fixing interface, the bone grafting area is provided with an upper oval opening and a lower oval opening, the front part of the macroscopic appearance structure is narrower than the rear part, the second-layer bionic structure is a structural unit body of the first-layer bionic structure, the structural unit bodies are connected in a space array manner, the structural unit bodies are particularly respectively arrayed in three directions of a space XYZ axis, the unit bodies are tangent to each other, the third-layer bionic structure is a appearance regulating structure of the second-layer bionic structure, and the fourth-layer bionic structure is a biological activating coating on the surface of the third-layer bionic structure; the hierarchical structure and the relationship are shown in fig. 5, and fig. 5 is only a schematic diagram, but the specific shape structure of each hierarchical layer is not limited to the one shown in fig. 5.

The fusion device with the multi-layer bionic active fusion function is constructed by taking goat neck 3-4 segments as objects. The preparation method comprises the following specific steps:

(1) Constructing a first-level bionic structure of the fusion device;

collecting neck CT data of a goat, reconstructing a goat neck 3-4 segment model by using MIICS software, calculating and extracting geometric features by using data processing software, and designing a macroscopic appearance structure of a fusion device;

(2) Constructing a second-level bionic structure of the fusion device;

the average CT value of 10 planar cancellous bones of the cervical 4 vertebral body is cut, and the elastic modulus is estimated through a formula. Simulating the real stress of the upper cone and the lower cone of the goat neck 3-4 segment after the implantation of the fusion cage through finite element analysis, and constructing a bone trabecula macro-porous structure of the fusion cage; mechanical property test is carried out on the fusion device, and the elastic modulus and the yield strength of the fusion device with different porous structures are tested; the macro-scale porous structure adopts a diamond structural unit body, the unit body has a width (namely a rod diameter) of 400 mu m, a pore diameter of 660 mu m, a designed porosity of 70.1%, an actual measurement porosity of 61.3%, a yield strength of 180.28MPa and an elastic modulus of 6.71GPa;

(3) Constructing a third-level bionic structure of the fusion device;

slicing the fusion device model, then guiding the sliced fusion device model into a printer, regulating and controlling the technological parameters of the printer, wherein the laser power is 100W, the scanning speed is 900mm/s, the printing interval is 190 mu m, and the powder spreading layer thickness is 25 mu m. The printed fusion device sample has a micro-nano-scale morphology structure, in particular an orderly arranged orthogonal porous structure with the size of 70-85 mu m;

(4) Constructing a fourth-level bionic structure of the fusion device;

preparing a NaOH solution with the concentration of 5mol/L, implanting a titanium alloy interbody fusion cage sample into the solution, reacting for 1 hour under the heat preservation condition of 60 ℃, washing and drying, performing sintering heat treatment, preserving heat for 1 hour at 600 ℃, and cooling along with a furnace at the heating rate of 5 ℃/min to generate 10-100 nm-sized nano sodium titanate crystals on the surface of the titanium alloy;

(5) The titanium alloy fusion cage obtained through the steps has a four-level bionic structure, particularly a diamond structure unit body mechanical bionic porous structure with millimeter scale personalized customized appearance and micrometer scale actual measurement porosity of 61.3%, a regularly arranged orthogonal porous structure with micrometer-nanometer scale 70-85 μm size, and nanometer-scale 10-100 nm-size sodium titanate crystals, wherein details are shown in figure 1.

Example 2

The diamond structure with 300 μm of unit edge width (namely the rod diameter) and 760 μm of pore diameter and 81.6% of designed porosity is selected as the unit body of the macroscopic porous structure. According to the method of example 1, the customization of the first-level millimeter-scale personalized macro-outline structure is firstly performed, then the design of the second-level macro-porous structure is performed, then the construction of the third-level micro-nano-scale surface topology structure is performed, finally the construction of the fourth-level nano-scale surface sodium titanate crystal bioactive coating is performed, and the other parameters are selected and the preparation process is the same as that of example 1, except that the example adjusts the parameters of the rod diameter, the pore diameter and the porosity of the second-level micro-scale macro-porous structure. Finally, the second-level bionic structure of the fusion device is a macroscopic porous structure of a diamond structure unit combination with the micrometer scale measured porosity of 74.4%, the mechanical property of the fusion device is changed, and compared with the embodiment 1, the yield strength is reduced by 48.8%, and the elastic modulus is reduced by 48.6%.

Example 3

According to the method of example 1, a multi-layer bionic active fusion cage was prepared, and the other parameters were selected and the preparation process was the same as in example 1, except that in this example, the parameters of the rod diameter, pore diameter, porosity of the second-layer microscale macroscopic porous structure were adjusted. Finally, the second-level bionic structure of the fusion device is a macroscopic porous structure of a diamond structure unit combination with a micrometer scale unit body width (namely a rod diameter) of 200 micrometers, a pore diameter of 860 micrometers, a designed porosity of 91.0 percent and an actual measured porosity of 87.3 percent, the mechanical property of the fusion device is changed, and compared with the embodiment 1, the yield strength is reduced by 80.1 percent, and the elastic modulus is reduced by 83.8 percent. .

Example 4

According to the method of example 1, a multi-level bionic active fusion cage was prepared, and the rest of the parameters were selected and the preparation process was the same as in example 1, except that in this example the printing process parameters of the third-level micro-nano scale surface topology were adjusted. The laser power was set at 40W, the scanning speed at 900mm/s, the printing interval at 190 μm, and the thickness of the powder layer at 25. Mu.m. The printed fusion device sample has a micro-nano-scale morphology structure, particularly a topological structure with an irregular arrangement of <100 mu m scale, the biological performance of the fusion device is changed, and compared with the fusion device in the embodiment 1, the cell proliferation rate is reduced, the cell distribution form is more irregular, and the detail is shown in the figure 2.

Example 5

According to the method of example 1, a multi-level bionic active fusion cage was prepared, and the rest of the parameters were selected and the preparation process was the same as in example 1, except that in this example the printing process parameters of the third-level micro-nano scale surface topology were adjusted. The laser power was set at 100W, the scanning speed at 900mm/s, the printing interval at 170 μm, and the thickness of the powder layer at 25. Mu.m. The printed fusion cage sample has a micro-nano-scale morphology structure, particularly a regularly arranged orthogonal porous structure with the size of 50-65 mu m, so that the biological performance of the fusion cage is changed, and compared with the fusion cage in the embodiment 1, the cell proliferation rate is increased, and the cell distribution form is more regular.

Example 6

According to the method of example 1, a multi-level bionic active fusion cage was prepared, and the rest of the parameters were selected and the preparation process was the same as in example 1, except that in this example the printing process parameters of the third-level micro-nano scale surface topology were adjusted. The laser power was set at 100W, the scanning speed at 900mm/s, the printing interval at 210 μm, and the thickness of the powder layer at 25. Mu.m. The printed fusion cage sample has a micro-nano-scale morphology structure, particularly a regular-arrangement orthogonal porous structure with the size of 90-105 mu m, so that the biological performance of the fusion cage is changed, and compared with the fusion cage in the embodiment 1, the cell proliferation rate is reduced, and the cell distribution morphology is more irregular.

Example 7

According to the method of example 1, a multi-level bionic active fusion cage was prepared, and the rest of the parameters were selected and the preparation process was the same as in example 1, except that in this example the printing process parameters of the third-level micro-nano scale surface topology were adjusted. The laser power was set at 100W, the scanning speed at 900mm/s, the printing interval at 190 μm, and the powder spreading layer thickness at 100. Mu.m. The printed fusion cage sample has a micro-nano-scale morphology structure, particularly a pore structure with irregular arrangement of 100-200 mu m scale, so that the biological performance of the fusion cage is changed, and compared with the fusion cage of the embodiment 1, the cell proliferation rate is reduced, and the cell distribution form is more irregular.

Example 8

This example differs from example 1 only in that: depositing a biological activated coating-100-1000 nm hydroxyapatite coating on the surface of the fusion device by the sodium titanate crystal layer obtained in the step (4) through an electrochemical deposition method, wherein the working parameters of the electrochemical deposition method are as follows: (1) The sample, the platinum plate and the saturated calomel electrode are respectively used as a cathode, an anode and a reference electrode; (2) the temperature of the electrolyte is 85 ℃; (3) CaCl (CaCl) ₂ ·6H ₂ O、NH ₄ H ₂ PO ₄ And NaCl in a molar ratio of 25:15:1.5; (4) washing with clear water and drying at room temperature; the specific operation process of electrochemical deposition is as follows: specific parameters and steps: after the alkaline heat treatment, electrodeposition (paramt 2273,Princeton Applied Research,USA) is performed at an electrochemical workstation; the processed sample is placed in a container, and air is pumped into a negative pressure state through a vacuum pump; then adding 2.5mM CaCl into the container ₂ 6H ₂ O、1.5mM NH ₄ H ₂ PO ₄ And an electrolyte of 0.15M NaCl; adopting a pulse current method and a three-electrode method; the sample, the platinum plate and the saturated calomel electrode are respectively used as a cathode, an anode and a reference electrode; the temperature of the electrolyte is 85 ℃; after deposition, the samples were washed with distilled water and dried at room temperature; the hydroxyapatite coating can be obtained to promote bone conductivity and bone inducibility; the rest steps and parameters are the same;see fig. 6 for details.

Comparative example 1

In this example, only the first hierarchical biomimetic structure of the cage is constructed. According to the method of embodiment 1, the neck CT data of the goat is firstly collected, the MIICS software is used for reconstructing a 3-4 segment model of the goat neck, geometric features are calculated and extracted through data processing software, a macroscopic appearance structure of the fusion cage is designed, and the parameter selection and construction method is the same as that of embodiment 1, except that the construction of a second, third and fourth-level bionic structure is not carried out in the embodiment. In this example, the obtained fusion device can only obtain the macroscopic appearance structure of the customized fusion device on the millimeter scale of the first level, and cannot obtain the macroscopic bionic mechanical porous structure constructed by the second-level micrometer scale bone-like trabecular structure, the microscopic topological structure constructed by the third-level micrometer-nanometer scale, the fourth-level nanometer-scale sodium titanate crystal topological structure and capillary micropores thereof. Therefore, the fusion device of the embodiment has compact structure and extremely high elastic modulus, is easy to cause stress shielding after implantation, causes adjacent bone fracture and bone absorption, and displacement, sinking and the like of the fusion device, and simultaneously does not reserve space for growth of cell colonies, blood vessels and new bone tissues, so that new bone cannot grow in, and bone fusion is difficult to realize. The fusion device has no surface micro-topological structure and bioactive coating, has poor biological performance, weak cell proliferation and adhesion capability, poor osteogenic differentiation capability, difficult generation of new bone, difficult formation of organic osseous combination between the body and the implant, low bone conductivity and low bone fusion rate.

Comparative example 2

In the embodiment, only the first-level bionic structure and the second-level bionic structure of the fusion device are constructed. The first and second hierarchical biomimetic structures of the fusion cage were constructed according to the method of example 1, and the parameter selection and construction method was the same as that of example 1, except that the third and fourth hierarchical biomimetic structures were not constructed in this example. In this example, the obtained fusion device can only obtain a macroscopic appearance structure of the customized fusion device on the millimeter scale of the first level, and a macroscopic bionic mechanical porous structure constructed by the second-level micrometer-scale bone-like trabecular structure, and cannot obtain a microscopic topological structure constructed by the third-level micrometer-nanometer scale, a fourth-level nanometer-scale sodium titanate crystal topological structure and capillary micropores thereof. Therefore, the fusion device of the embodiment has no surface micro-topological structure and bioactive coating, has poor biological performance, does not provide larger surface area for adsorbing protein and cells, has poor permeability of a bracket, is difficult to induce new bone formation, is difficult to form organic bone bonding between an organism and an implant, has low bone conductivity and low bone fusion rate, and is shown in the detail of figure 3.

Comparative example 3

In the embodiment, only the first, second and third-level bionic structures of the fusion device are constructed. The first, second, and third hierarchical biomimetic structures of the fusion cage were constructed according to the method of example 1, and the parameter selection and construction method was the same as example 1, except that the fourth hierarchical biomimetic structure was not constructed in this example. In the embodiment, the obtained fusion device can only obtain a macroscopic appearance structure of the customized fusion device on the millimeter scale of the first level, a macroscopic bionic mechanical porous structure constructed by a second-level micrometer-scale bone-like trabecular structure, and a microscopic topological structure constructed by the third-level micrometer-nanometer scale, and can not obtain a fourth-level nanometer-scale sodium titanate crystal topological structure and capillary micropores thereof. Therefore, the fusion device of the embodiment has no surface bioactive coating, poor biological performance and no hydroxyapatite coating to induce the rapid generation of new bone, the organic bone combination formed between the body and the implant is slower, the quality is poorer, the bone fusion rate is lower, the speed is slower, and the detail is shown in figure 4.

The features and capabilities of the present invention are described in further detail below in connection with the examples. The foregoing is merely illustrative and explanatory of the invention as it is claimed, as modifications and additions may be made to, or similar to, the particular embodiments described, without the benefit of the inventors' inventive effort, and as alternatives to those of skill in the art, which remain within the scope of this patent.

Claims (8)

1. The fusion device with the multi-layer bionic active fusion function is characterized by comprising a four-layer bionic structure, wherein the first-layer bionic structure is a macroscopic appearance structure of the fusion device, the second-layer bionic structure is a structural unit body of the first-layer bionic structure, the structural unit body is a macroscopic porous structure, the third-layer bionic structure is a morphology regulation structure of the second-layer bionic structure, the morphology regulation structure is a micro-nano topological structure, and the fourth-layer bionic structure is a biological activation coating on the surface of the third-layer bionic structure;

the fusion device with the multi-layer bionic active fusion function is prepared by the following method:

step 1, constructing a fusion device model with a first-level bionic structure and a second-level bionic structure, wherein the specific process is as follows:

step 1.1, reconstructing a focus model;

step 1.2, constructing a first-level bionic structure of the fusion device according to the focus model obtained in the step 1.1;

step 1.3, calculating upper and lower cone stress of an implantation area of the fusion device through finite element analysis and algorithm, and simulating to construct a second-level bionic structure of the fusion device;

step 2, constructing a third-level bionic structure of the fusion device according to the fusion device model obtained in the step 1, and obtaining the fusion device with the third-level bionic structure;

and 3, biologically activating the fusion device with the three-level bionic structure obtained in the step 2, and constructing a fourth-level bionic structure of the fusion device to obtain the fusion device with the multi-level bionic active fusion function.

2. The fusion cage of multi-level biomimetic active fusion functions of claim 1, wherein the dimensions of the first-level biomimetic structure are millimeter dimensions.

3. The multi-level bionic active fusion cage according to claim 1, wherein the second-level bionic structure has a micrometer scale, a porosity of 70% -90% and a pore size of 600-900 μm.

4. The fusion device of claim 1, wherein the third level biomimetic structure has a micro-nano scale and a pore size of 20-200 μm.

5. The fusion device of claim 1, wherein the fourth-level biomimetic structure has a nanoscale pore size of 10-1000nm.

6. The fusion device with the multi-level bionic active fusion function according to claim 1, wherein the specific process of reconstructing the lesion model in step 1.1 is as follows: patient lesion CT data was acquired and the lesion model was identified and reconstructed using MIMICS software.

7. The fusion device with the multi-level bionic active fusion function according to claim 1, wherein the specific process of the step 2 is as follows: and (3) introducing the fusion device model with the first-level bionic structure and the second-level bionic structure obtained in the step (1) into a 3D printer, and constructing a third-level bionic structure of the fusion device through a laser selective fusion technology to obtain the fusion device with the third-level bionic structure.

8. The fusion device with the multi-level bionic active fusion function according to claim 1, wherein the process of biological activation in the step 3 is as follows:

step 3.1, placing the fusion device in an alkaline solution, and reacting for 1-3 hours at the temperature of 55-75 ℃ to generate sodium titanate hydrogel;

and 3.2, drying the sodium titanate hydrogel obtained in the step 3.1, performing sintering heat treatment, preserving heat at 500-700 ℃ for 1-3 hours, and cooling along with a furnace at a heating rate of 4-7 ℃/min, and dehydrating the hydrogel to obtain sodium titanate crystals, thereby obtaining a sodium titanate crystal layer.

Images