A method for manufacturing a bone repair material, a bone repair material

Abstract

The application provides a bone repair material manufacturing method and a bone repair material, and relates to the technical field of metamaterials. The bone repair material is formed by a unit cell structure, the outline of the unit cell structure is a cube, the cube has two opposite surfaces and four side surfaces enclosed between the two surfaces, and the unit cell structure is formed by a plurality of first beams and second beams. The bone repair material manufacturing method comprises the following steps: constructing a first unit cell structure model, the first beams and the second beams of the first unit cell structure are both straight rods; forming the first beams and the second beams by using a minimal surface structure to obtain a third unit cell structure model; performing spatial array on the third unit cell structure model to obtain an array structure model; and manufacturing the array structure model based on an additive manufacturing process to obtain the bone repair material. The bone repair material prepared by the bone repair material manufacturing method can be effectively matched with a bone implantation object.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of metamaterials, and particularly relates to a bone repair material manufacturing method and a bone repair material. BACKGROUND

[0002] Bone defect is one of the most common injuries in clinic, has a high rate of disability and strong destructiveness to human health. With the growth of age, human bones inevitably age, have osteoporosis or even necrosis to cause bone defects. In addition, a large number of patients also face the problem of bone defects due to traffic accidents and orthopedic diseases. When the bone defect exceeds a critical threshold, osteoblasts are insufficient for repair.

[0003] In the related art, a bone implant is used to replace the damaged or missing bone of a patient. The bone implant should generally have a similar elastic modulus to human bone to avoid stress shielding effects, and the existing bone implant lacks reusability. SUMMARY

[0004] The present application aims to provide a bone repair material manufacturing method and a bone repair material to solve the technical problem that the bone implant is difficult to reuse.

[0005] To achieve the above-mentioned purpose, the present application provides the following technical solutions.

[0006] In a first aspect, the present application provides a bone repair material manufacturing method, wherein the bone repair material is formed by a unit cell structure, the outline of the unit cell structure is a cube, the cube has two opposite surfaces and four side surfaces arranged between the two surfaces, and the unit cell structure is formed by a plurality of first beams and second beams; the manufacturing method comprises the following steps:

[0007] constructing a first unit cell structure model, wherein the first beams and the second beams of the first unit cell structure are straight rods;

[0008] forming the first beams and the second beams using a minimal surface structure to obtain a third unit cell structure model;

[0009] performing spatial array on the third unit cell structure model to obtain an array structure model;

[0010] manufacturing the bone repair material based on the array structure model using an additive manufacturing process.

[0011] According to at least one embodiment of the present application, before the first beams and the second beams are formed using a minimal surface structure to obtain a third unit cell structure model, the method further comprises the following steps:

[0012] replacing the first beams and the second beams in the first unit cell structure model with at least a semicircular arc-shaped rod to obtain a second unit cell structure model.

[0013] According to at least one embodiment of the present application, in the second cell structure model, the first beam is a semicircular first beam, and the circular arc shape of the second beam is a quarter circular arc shape.

[0014] According to at least one embodiment of the present application, the first beam and the second beam are formed using a minimal surface structure to obtain a third cell structure model, comprising:

[0015] The cell structure cube is divided into a plurality of sub-cubes, and the lattice of the minimal surface structure is filled in each sub-cube. The intersection of the lattice in each sub-cube and the first beam and the second beam of the cell structure is obtained by Boolean operation.

[0016] According to at least one embodiment of the present application, the additive manufacturing process includes a selective laser melting process.

[0017] According to at least one embodiment of the present application, the laser power of the selective laser melting process is 130W-150W, the powder layer thickness is 20μm-40μm, and the hatch spacing is 70μm-90μm.

[0018] According to at least one embodiment of the present application, the scanning speed of the selective laser melting process is negatively correlated with the austenite phase transition peak temperature of the bone repair material.

[0019] According to at least one embodiment of the present application, the austenite phase transition peak temperature of the bone repair material ranges from 36℃ to 42℃.

[0020] According to at least one embodiment of the present application, the shape memory alloy includes one of a copper-based shape memory alloy, an iron-based shape memory alloy, and a nickel-titanium-based shape memory alloy.

[0021] According to at least one embodiment of the present application, the copper-based shape memory alloy includes one of Cu-Zn, Cu-Zn-Al, Cu-Zn-Sn, Cu-Zn-Si, Cu-Zn-Ga, and Cu-Sn alloy.

[0022] According to at least one embodiment of the present application, the iron-based shape memory alloy includes one of Fe-Pt, Fe-Mn-Si, Fe-Ni-Co-Ti, Fe-Mn-Al-Ni, and Fe-C-Mn-Si-Cr-Ni alloy.

[0023] According to at least one embodiment of the present application, the nickel-titanium-based shape memory alloy includes one of Ni-Ti-Cu, Ni-Ti-Co, Ni-Ti-Fe, and Ni-Ti-Nb alloy.

[0024] According to at least one embodiment of the present invention, the stiffness and strength of the bone repair material can be adjusted based on changes in ambient temperature.

[0025] According to at least one embodiment of the present invention, when the temperature is raised to 42°C, the recovery rate of the bone repair material under cyclic static compression is at least 98%.

[0026] According to at least one embodiment of the present invention, both the first beam and the second beam are formed of a minimal curved surface structure.

[0027] According to at least one embodiment of the present invention, the cross-section of the second beam is circular.

[0028] According to at least one embodiment of the present invention, a cell structure for bone repair is provided, the cell structure having a cube-shaped outline, the cube having two opposing surfaces and four side surfaces surrounding the two surfaces, each surface having a first node located at the center of the surface and four third nodes located at the vertices of the cube, each side surface having a second node located at the center of the side surface, and the cube also having a fourth node located at the center of the cube.

[0029] The cell structure also includes multiple semi-circular first beams and circular second beams.

[0030] Each side is formed by two first beams, and in the same side, the apex of the arc of the two first beams is connected to the second node, and the two ends of each first beam are respectively connected to two third nodes on the same surface;

[0031] Each of the surfaces is formed by two first beams, and in the same surface, the apex of the arc of the two first beams is connected to the first node, and the two ends of each first beam respectively form the third node;

[0032] Each of the second nodes is connected to the first node via the second beam;

[0033] The second nodes of two adjacent sides are connected by the second beam;

[0034] Both the first beam and the second beam are formed by minimal curved surface structures.

[0035] According to at least one embodiment of the present invention, the arc shape of the second beam is a quarter-circle arc.

[0036] According to at least one embodiment of the present invention, the apex of the arc of each of the second beams connecting the first node and the second node is close to the fourth node.

[0037] According to at least one embodiment of the present invention, the apex of the arc of each of the second beams connected between the second nodes of two adjacent sides is close to the fourth node.

[0038] According to at least one embodiment of the present invention, both the first beam and the second beam are formed of a Gyroid three-period minimal surface structure.

[0039] According to at least one embodiment of the present invention, the outer contour of the unit cell of the Gyroid three-periodic minimal surface structure is located within the sub-cubic structure.

[0040] According to at least one embodiment of the present invention, the cross-section of the second beam is circular.

[0041] The metamaterial for bone repair of the present invention is formed by an array of multiple cell structures, wherein the cell structure is the cell structure described in the first aspect;

[0042] In the two fitted cell structures, the two second beams corresponding to different cell structures are arranged in a semi-circular shape.

[0043] According to at least one embodiment of the present invention, the stiffness, porosity, and pore size of the metamaterial are decoupled.

[0044] According to at least one embodiment of the present invention, the diameter of the second beam, the wall thickness of the Gyroid unit cell, and the stiffness of the metamaterial are positively correlated; and / or,

[0045] The size of the Gyroid unit cell is negatively correlated with the stiffness of the metamaterial.

[0046] In one or more technical solutions provided in the exemplary embodiments of the present invention, at least one of the following beneficial effects can be achieved.

[0047] In the bone repair material of an exemplary embodiment of the present invention, the cell structure is generally a cubic frame structure, including two opposing surfaces and four side surfaces surrounding the two surfaces. Each surface and each side surface is formed by two first beams. On the same side surface, the arc apex of the two first beams connects to a second node (the center point of the face of that side surface), and the connecting segments of each first beam connect to two third nodes on the same surface. On the same surface, the arc apex of the two first beams connects to a first node (the center point of the face of that surface), and the two ends of each first beam form third nodes (vertices of the cube). The cube also has a fourth node (the center point of the cube). Each second node is connected to the first node, and the second nodes of adjacent side surfaces are connected by second beams. The cell structure is arranged in a face-centered cubic pattern, exhibiting high specific strength. Compared to setting the first and second beams as straight rods, setting the first beams as semi-circular arc structures and the second beams as circular arc structures further improves the overall stiffness and strength of the cell structure.

[0048] Furthermore, both the first and second beams are formed using minimal curved surface structures. These minimal curved surface structures are integrated with the macroscopic cell structure, allowing the stiffness, porosity, and pore size of the cell structure to be decoupled. Through the controllability of this material, the implant used for bone repair can meet the complex needs of various implants, thereby improving the fusion effect with bone.

[0049] Furthermore, the metamaterial formed by the cell structure is made by 3D printing of shape memory alloy, and the phase transition temperature of the shape memory alloy is controlled at a preset temperature. Before implanting the bone repair material, it is compressed and shaped, and the structure is pre-programmed. After implantation, heating technology is used to raise the temperature without damaging the human body, so that the structure returns to its original shape, thus allowing the bone repair material to be implanted in a small space. Attached Figure Description

[0050] The accompanying drawings illustrate exemplary embodiments of the invention and, together with the description thereof, serve to explain the principles of the invention. These drawings are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification.

[0051] Figure 1 This is an isometric structural diagram of a cell structure according to an embodiment of the present invention;

[0052] Figure 2 This is a front view schematic diagram of the cell structure according to an embodiment of the present invention;

[0053] Figure 3 This is a schematic diagram illustrating the design principle of the cell structure according to an embodiment of the present invention;

[0054] Figure 4These are stress-strain curves before and after macroscopic optimization of the cell structure according to an embodiment of the present invention;

[0055] Figure 5 These are stress-strain curves of metamaterials with different rod diameters according to embodiments of the present invention;

[0056] Figure 6 These are stress-strain curves of metamaterials with different wall thicknesses according to embodiments of the present invention;

[0057] Figure 7 These are stress-strain curves of metamaterials with different microscopic cell sizes according to embodiments of the present invention;

[0058] Figure 8 These are the stiffness values ​​of metamaterials with different geometric parameters according to embodiments of the present invention;

[0059] Figure 9 This is a CCK-8 count of human bone marrow mesenchymal stem cells under different extraction liquid fractions according to an embodiment of the present invention.

[0060] Figure 10 This is a diagram showing the results of an alizarin red staining experiment on osteoblasts using metamaterials according to an embodiment of the present invention;

[0061] Figure 11 The figure shows the experimental results of vascular endothelial cell migration and invasion of the metamaterial according to an embodiment of the present invention, where (a) is the migration rate and (b) is the invasion rate.

[0062] Figure 12 These are differential thermal scanning analysis curves of metamaterials according to embodiments of the present invention;

[0063] Figure 13 This is the metamaterial recovery rate-time curve at 42°C according to an embodiment of the present invention;

[0064] Figure 14 These are stress-strain curves of metamaterials under cyclic compression according to embodiments of the present invention;

[0065] Figure 15 These are stress-strain curves of the metamaterial at different temperatures according to embodiments of the present invention.

[0066] Figure 16 The figures show the experimental results of (a) osteogenic gene ALP and (b) RUNX2 gene expression of metamaterials according to embodiments of the present invention.

[0067] Figure 17 This is a schematic diagram of a bone repair material manufacturing method according to an embodiment of the present invention;

[0068] Figure 18 This is a diagram showing the results of a vascular endothelial cell scratch test on a bone repair material according to an embodiment of the present invention.

[0069] Figure 19 This is an experimental result diagram of vascular endothelial cell lumen formation of the bone repair material according to an embodiment of the present invention.

[0070] Reference numerals: 10, surface; 20, side; 31, first node; 32, second node; 33, third node; 34, fourth node; 41, first beam; 42, second beam. Detailed Implementation

[0071] To make the technical problems to be solved, the technical solutions, and the beneficial effects of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0072] Bone defects are one of the most common injuries in clinical practice, with a high rate of disability and significant damage to human health. With age, bone aging, osteoporosis, and even necrosis inevitably occur, leading to bone defects. Furthermore, a large number of patients also face bone defects due to traffic accidents and orthopedic diseases. When bone defects exceed a critical threshold, osteoblast repair becomes insufficient.

[0073] Bone grafting is one approach to repairing bone defects, but existing bone implants are difficult to use in confined spaces and are difficult to implant.

[0074] To address the aforementioned issues, the bone repair material manufacturing method provided by the exemplary embodiment of this invention employs a multi-biomimetic strategy combining two biomimetic structures in the cell structure during model construction. By improving upon the Octet lattice structure and incorporating the U-shaped arch from a tortoise shell structure, the beams forming the Octet lattice structure are formed using a biocompatible minimal curved surface structure. This decouples the stiffness, pore size, and porosity of the metamaterial, allowing for individual control of the metamaterial's adaptation to the bone at the implantation site. Furthermore, the metamaterial formed by the cell structure is made of shape memory alloy, with the phase transition temperature of the shape memory alloy controlled at a preset temperature. Before implantation, the bone repair material is compressed and shaped, and its structure is pre-programmed. After implantation, heating technology is used to raise the temperature without damaging the human body, causing the structure to return to its original shape, thus enabling the bone repair material to be implanted into a confined space.

[0075] Figure 1 This is an isometric structural diagram of a cell structure according to an embodiment of the present invention; Figure 2 This is a front view schematic diagram of the cell structure according to an embodiment of the present invention. Figure 1 and Figure 2As shown, in the cellular structure provided by the exemplary embodiment of the present invention, the outline of the cellular structure is a cube. The cube has two opposing surfaces 10 and four side surfaces 20 surrounding the two surfaces 10. Each surface 10 has a first node 31 located at the center of the surface 10 and four third nodes 33 located at the vertices of the cube. Each side surface 20 has a second node 32 located at the center of the side surface 20. The cube also has a fourth node 34 located at the center of the cube. The cellular structure also includes a plurality of semi-circular first beams 41 and circular second beams 42. Each side surface 20 is formed by two first beams 41. On the same side 20, the apex of the arc of the two first beams 41 is connected to the second node 32, and the two ends of each first beam 41 are respectively connected to the two third nodes 33 on the same surface 10; each surface 10 is formed by two first beams 41, and on the same surface 10, the apex of the arc of the two first beams 41 is connected to the first node 31, and the two ends of each first beam 41 respectively form the third node 33; each second node 32 is connected to the first node 31 by a second beam 42; the second nodes 32 of two adjacent sides 20 are connected by a second beam 42; both the first beam 41 and the second beam 42 are formed by minimal curved surface structures.

[0076] For example, the two first beams 41 on side 20 are arranged with their openings facing away from each other, that is, the opening of each first beam 41 faces the adjacent surface 10, and its two ends are respectively connected to two third nodes 33 on the adjacent surface 10. The two first beams 41 on surface 10 are also arranged with their openings facing away from each other, and the four ends of the two first beams 41 on the same surface 10 are respectively connected to four third nodes 33 on the surface 10. The arrangement of the first beams 41 on the two surfaces 10 can be the same or different. When the arrangement is different, the ends of the first beams 41 on one surface 10 are respectively connected to the third nodes 33 on two opposite side 20, and the ends of the first beams 41 on the other surface 10 are respectively connected to the third nodes 33 on two other opposite side 20.

[0077] For example, the first node 31 is connected to the second node 32 by the second beams 42, and the openings of the eight second beams 42 all face the periphery of the macro cube. For example, adjacent second nodes 32 are connected by the second beams 42, and the openings of the four second beams 42 all face the periphery of the macro cube.

[0078] Figure 3 This is a schematic diagram illustrating the design principle of the cell structure according to an embodiment of the present invention. Figure 3As shown, the design concept of the cell structure provided by the exemplary embodiment of the present invention is as follows: the lattice includes macroscopic cells, the general outline of which is a cube, and the crystal structure is generally a face-centered cubic arrangement of metal atoms, which has the characteristic of high specific strength. The macroscopic cell includes eight vertices of a virtual cube, namely eight third nodes 33, six face center points, namely two first nodes 31 on the two surfaces 10 and four second nodes 32 on the four sides 20, and a fourth node located at the center of the virtual cube. Before macroscopic optimization, the first beam 41 and the second beam 42 between the nodes are straight rods, based on the U-shaped arch in the tortoise shell structure. After macroscopic optimization, they are curved rods, wherein the first beam 41 is a semi-circular arc rod, and the second beam 42 is a rod smaller than a semi-circular arc, for example, the second beam 42 is a quarter-circular arc rod.

[0079] Figure 4 The stress-strain curves of the cell structure before and after macroscopic optimization according to an embodiment of the present invention are shown. (Refer to...) Figure 4 As shown, the above-mentioned macroscopic size optimization can further improve the stiffness and strength of the crystal structure.

[0080] When the second beam 42 is a quarter-circle arc rod, after the cell structure forms a metamaterial, the two adjacent cell structures at the second node 32 on the side 20, since the openings of the second beam 42 all face the outer periphery of the macroscopic cube, when the two cell structures are spliced ​​together, the corresponding second beam 42 in the two different cell structures presents a U-shaped arch setting, so that the metamaterial structure is a U-shaped arch structure both on the cube surface and inside, thereby increasing the stiffness and strength of the metamaterial.

[0081] Figure 17 This is a schematic diagram of a bone repair material manufacturing method according to an embodiment of the present invention. Figure 17 As shown, the manufacturing method includes the following steps:

[0082] Step 101: Construct the first cell structure model. The first beam 41 and the second beam 42 of the first cell structure are both straight rods.

[0083] For example, the first cell structure is a macroscopic cubic frame structure, constructed based on the Octet lattice structure. Then, based on the U-shaped arch in the tortoise shell structure, the first beam 41 and the second beam 42 are structurally optimized. For example, the first beam 41 is a semi-circular arc rod, and the second beam 42 is a quarter-circular arc rod, thus obtaining the second cell structure model.

[0084] Step 102: The first beam 41 and the second beam 42 are formed using minimal surface structures to obtain the third cell structure model.

[0085] like Figure 3As shown, after optimizing the macroscopic scale of the cell structure, further optimization is performed at the microscopic scale, for example, by using minimal curved surface structures to form individual beams, so that the cell structure has excellent biocompatibility.

[0086] Minimal surfaces are surfaces with an average curvature of zero. There are various forms of minimal surface structures, such as Costa series minimal surfaces - single-cycle, Cobogo House minimal surfaces - double-cycle, FRD(r)Surface - triple-cycle, etc.

[0087] For example, in the cellular structure provided by the exemplary embodiment of the present invention, the first beam 41 and the second beam 42 are both formed by a Gyroid three-period minimal surface structure. When this Gyroid three-period minimal surface structure is integrated with the macroscopic cellular structure, the size of the macroscopic cube and the size of the microscopic cube are selected, wherein the macroscopic cube contains multiple microscopic virtual sub-cubes, and the microscopic virtual cubes are filled with a Gyroid lattice, thus filling the macroscopic cellular structure with the microscopic structure, thereby forming the cellular structure of a dual-scale lattice metamaterial. Figure 3 As shown, in the macroscopic structural parameters of the cell structure, the unit cell length is L, which is the edge length of the macroscopic virtual cube; the diameter of the second beam 42 is R, meaning that the virtual cross-sections of both the second beam 42 and the first beam 41 are circular, with R being the diameter of the circle. In the microscopic structural parameters, the unit cell length of the Gyroid lattice is c, and the wall thickness is h. It should be noted that after the macroscopic cell structures are bonded together to form a metamaterial, the cross-section of the first beam 41 is also circular.

[0088] Step 103: Spatial array the third cell structure model to obtain the array structure model.

[0089] An exemplary embodiment of the present invention also provides a metamaterial for bone repair, which is formed by an array of multiple cell structures, the cell structure being the cell structure in the above embodiment; in two attached cell structures, the two corresponding second beams 42 in different cell structures are arranged in a semi-circular manner, that is, each cell structure is attached to each other to form an array structure of the metamaterial.

[0090] Step 104: Based on the array structure model, the bone repair material is produced using additive manufacturing technology.

[0091] Metamaterials for bone repair are 3D printed in a single piece. The metamaterials can be made of various alloys, such as magnesium alloys, zinc alloys, aluminum alloys, titanium alloys, stainless steel, copper alloys, cobalt-based alloys, zirconium-based alloys, etc. For example, selective laser melting (SLM) is used for fabrication.

[0092] For example, the deformable bone repair material can be one of copper-based shape memory alloys, iron-based shape memory alloys, or nickel-titanium-based shape memory alloys.

[0093] For example, copper-based shape memory alloys include one of Cu-Zn, Cu-Zn-Al, Cu-Zn-Sn, Cu-Zn-Si, Cu-Zn-Ga, and Cu-Sn alloys; iron-based shape memory alloys include one of Fe-Pt, Fe-Mn-Si, Fe-Ni-Co-Ti, Fe-Mn-Al-Ni, and Fe-C-Mn-Si-Cr-Ni alloys; and nickel-titanium-based shape memory alloys include one of Ni-Ti-Cu, Ni-Ti-Co, Ni-Ti-Fe, and Ni-Ti-Nb alloys.

[0094] Figure 12 These are differential thermal scanning analysis curves of metamaterials according to embodiments of the present invention. For example... Figure 12 As shown, the sample was prepared using SLM 3D printing technology with nickel-titanium alloy as the substrate. The laser power was 140W, the powder layer thickness was 30μm, the hatch scanning spacing was 80μm, the scanning speed was 1000~1100mm / s, and the peak temperature of the austenitic phase transformation of the prepared sample was Ap.

[0095] For example, the peak temperature Ap of the austenitic phase transformation of the nickel-titanium alloy substrate is controlled according to the scanning speed s, and the relationship between the two satisfies Equation 1:

[0096]

[0097] The SLM nickel-titanium alloy 3D printing process parameters include a laser power of 140W, a powder layer thickness of 30μm, a hatch scanning spacing of 80μm, a scanning speed range from 1000mm / s to 1100mm / s, and a controlled austenitic phase transformation peak temperature of 36℃~42℃.

[0098] Figure 13 This is the metamaterial recovery rate-time curve at 42°C for a metamaterial according to an embodiment of the present invention. Figure 13 As shown, the bone repair material was subjected to quasi-static compression at room temperature and then shaped. After shaping, a recovery experiment was conducted at 42°C. The shape recovery rate reached approximately 98% after heating to 42°C. This indicates that the bone repair material has high reliability in the "implantation-recovery" process.

[0099] Figure 14 This is the stress-strain curve of the metamaterial under cyclic compression according to an embodiment of the present invention. Figure 14As shown, the bone repair material was subjected to ten cycles of quasi-static compression. The bone repair material was compressed at room temperature until it fractured. After unloading, it was heated to above the peak temperature of the austenitic phase transformation of the nickel-titanium alloy, for example, 42°C. This compression operation was repeated ten times. This shows that the bone repair material has strong mechanical stability and high recovery rate under cyclic compression, and has good reusability.

[0100] In practical applications, bone repair materials are compressed and shaped, and their structure is pre-programmed. After implantation, they are slowly heated to 42°C using nickel-based ferromagnetic eddy current induction. This heating process, which does not damage the human body, allows the structure to return to its original shape, thus enabling the implantation of bone repair materials in confined spaces.

[0101] Figure 15 These are stress-strain curves of the metamaterial according to an embodiment of the present invention at different temperatures. Compression experiments were conducted on the metamaterial at different temperatures, such as... Figure 15 As shown, the metallographic structure of nickel-titanium alloys can be adjusted by temperature to obtain different stiffness and strength. When the temperature reaches near the peak temperature of austenite transformation, the higher the temperature, the greater the volume fraction of austenite, and the greater the stiffness of the bone repair material.

[0102] The following experiments will use nickel-titanium alloy as an example and should not be construed as limiting the material of the metamaterial of this invention.

[0103] For example, with a macroscopic cubic unit cell length L = 20 mm, various metamaterial samples were printed by changing the macroscopic geometric parameters of the rod diameter R and the microscopic geometric parameters of the Gyroid unit cell size c and Gyroid wall thickness h. The sample name represents the numerical value of the geometric parameters. Taking sample number 1 as an example, the geometric parameters of sample R36c30h80 are: R = 3.6 mm, c = 3.0 mm, h = 0.8 mm. The porosity and pore size of the prepared samples are shown in Table 1.

[0104] Table 1 Metamaterial samples under different geometric parameters

[0105]

[0106] As shown in Table 1, a comparison of the data of sample 1 with samples 5, 6, and 8 reveals that the porosity and pore size are decoupled through the dual-scale (macro-scale and micro-scale) geometric parameter control of the cell structure in the exemplary embodiment of this invention.

[0107] Since the porosity of human bone cancellous tissue is between 50% and 90%, and the pore size required for cell growth is between 300 μm and 600 μm, as shown in Table 1, the porosity of the metamaterial can be adjusted between 50% and 90% by separately controlling the geometric parameters of the cell structure. This porosity range facilitates the transport and sufficient flow of nutrients within the bone. Simultaneously, the diameter of the micropores can also be adjusted between 150 μm and 700 μm. When the diameter of the micropores is within the range of 300 μm to 600 μm, it allows human bone cells to easily adhere, proliferate, and differentiate on this material. Therefore, when the metamaterial of the exemplary embodiment of this invention is used for bone defect repair, both porosity and pore size can be controlled separately to adapt to bone implantation requirements, which is more conducive to the growth needs of cells at different implantation sites.

[0108] Figure 5 These are stress-strain curves of metamaterials with different rod diameters according to embodiments of the present invention. Figure 5 As shown, compression tests were conducted on samples made of metamaterials. As the rod diameter R increased, both stiffness and strength increased.

[0109] Figure 6 These are stress-strain curves of metamaterials with different wall thicknesses according to embodiments of the present invention. Figure 6 As shown, compression experiments were conducted on samples made of metamaterials. As the wall thickness h of the Gyroid structure increased, both the stiffness and strength increased.

[0110] Figure 7 These are stress-strain curves of metamaterials with different microscopic cell sizes according to embodiments of the present invention. For example... Figure 7 As shown, compression experiments were conducted on samples fabricated from metamaterials. As the unit cell size *c* of the Gyroid structure decreased, both stiffness and strength increased. Compared to the rod diameter *R* and the wall thickness *h* of the Gyroid structure, the unit cell size *c* has a more significant impact on the stiffness and strength of the metamaterial.

[0111] Figure 8 These are the stiffness values ​​of metamaterials with different geometric parameters according to embodiments of the present invention. For example... Figure 8As shown, by varying different geometric parameters—rod diameter R, Gyroid structure wall thickness h, and Gyroid structure unit cell size c—samples 1 to 10 can smoothly transition from approximately 100 MPa to over 1000 MPa. This not only provides a wide adjustment range but also allows for high-precision customization of the stiffness value within that range. Since the porosity of human bone cancellous tissue is 50%–90%, the pore size required for cell growth is 300 μm–600 μm, and the elastic modulus is 50 MPa–800 MPa, the metamaterial of this exemplary embodiment can be adapted to the implantation site in terms of stiffness, porosity, and pore size. This achieves decoupling of stiffness, porosity, and pore size. Stiffness can also be adapted while meeting porosity requirements, avoiding stress shielding effects. In other words, pore size, stiffness, and porosity can be controlled separately within a wide range. This allows for the provision of the most suitable pore size for cell adhesion, growth, and nutrient transport in the implanted object, while adapting to the stiffness and strength of the implanted object and avoiding stress shielding.

[0112] Stress shielding effect refers to the phenomenon where, after fracture fixation, the use of high-stiffness and-strength bone plates for fixation is clinically recommended. This method provides a stable mechanical environment for the fractured tissue in the short term, preventing further injury and providing solid support, which is beneficial for patients to perform normal activities during rehabilitation. However, because the stiffness of the bone plate is much greater than that of the bone tissue, the bone tissue remains at a low stress level for an extended period. In the later stages of fracture rehabilitation, the bone tissue may develop osteoporosis due to insufficient mechanical stimulation. Refracture is also common after the bone plate is removed. Generally, the longer the fixation time, the worse the mechanical properties of the bone.

[0113] To further illustrate the biocompatibility of the metamaterials in the exemplary embodiments of the present invention, an example sample named R40c30h80 was selected for testing. The porosity, pore size, and elastic modulus of this sample are compatible with human vertebrae. Cell culture extracts were prepared using this sample for cell culture and observation.

[0114] The testing process is as follows: The 3D printed metamaterial sample (R40c30h80) was disinfected by soaking in 75% alcohol for 1 hour, and then extracted for 72 hours according to ISO 10993 Part 12 at an extraction ratio of 0.1 g / ml and then added to the cell culture medium.

[0115] Human BMSCs were cultured in a special medium and in a constant temperature incubator at 5% CO2, 37°C and saturated humidity with the lid loose. The medium was changed every 1-2 days. When the cells reached 80% confluence, they were digested and passaged.

[0116] HUVEC cells were cultured in a dedicated complete culture medium and cultured in a constant temperature incubator at 5% CO2, 37°C and saturated humidity with the lid loose. The medium was changed every 1-2 days. When the cells reached 80% confluence, they were digested and passaged.

[0117] All experiments included a control group that was cultured without the extract.

[0118] The culture medium was stained and observed under a microscope to observe and analyze the biological behavior and activity of human BMSC cells and their differentiated osteoblasts, as well as HUVEC cells.

[0119] Figure 9 This is a CCK-8 count map of human bone marrow mesenchymal stem cells under different extraction liquid fractions according to an embodiment of the present invention. Figure 9 As shown, the changes in cell viability of human BMSCs on days 1, 3, and 7 were detected using CCK-8 assay.

[0120] Specifically, metamaterial extracts at concentrations of 10%, 20%, 50%, and 100% were added to human BMSC cells for 1, 3, and 7 days. CCK8 staining and counting buffer was added to each well, and the absorbance at 450 nm was measured using a microplate reader. Higher absorbance indicated a greater number of cells, meaning more significant cell proliferation and higher cell viability. The test results are as follows: Figure 9 As shown, the metamaterial of the present invention, which can be used for bone repair, has high compatibility with human BMSC cells in its extract and has no significant effect on the cell activity and proliferation behavior.

[0121] Figure 10 This is a diagram showing the results of an alizarin red staining experiment on osteoblasts using metamaterials according to an embodiment of the present invention. The absorbance of differentiated, cultured, and alizarin red-stained osteoblasts was measured, and the test results are as follows. Figure 10 As shown, the absorbance of alizarin red staining in osteoblasts increased after the addition of metamaterial extract, indicating that the metamaterial extract increased the number of calcium nodules in osteoblasts, meaning that metamaterials have a promoting effect on osteoblast growth.

[0122] Figure 11 This is a diagram showing the experimental results of vascular endothelial cell migration and invasion using a metamaterial according to an embodiment of the present invention. HUVEC cells were cultured to a certain quantity and then placed in one of two separate chambers separated by a thin membrane, allowing cells to shuttle through. After 72 hours of culture, the total number of cells that had shuttled through the other chamber was counted. Figure 11 As shown, the total number of cells in the other chamber of the HUVEC cell migration and invasion assay increased after the addition of metamaterial extract. This indicates that metamaterials promote the activity and proliferation of HUVEC cells.

[0123] Figure 16 The figures show the experimental results of (a) osteogenic gene ALP and (b) RUNX2 gene expression in metamaterials according to embodiments of the present invention. Figure 16 As shown, differentiated and cultured osteoblasts underwent RNA extraction and reverse transcription, followed by quantitative polymerase chain reaction (PCR) to detect the expression levels of osteoblast genes ALP and RUNX2. The addition of the metamaterial extract significantly increased the expression levels of ALP and RUNX2 genes in osteoblasts. Therefore, the exemplary bone repair material of this invention promotes osteoblast growth.

[0124] Figure 18 This image shows the results of a scratch assay on vascular endothelial cells of the bone repair material according to an embodiment of the present invention. HUVEC cells were cultured to a certain quantity, scratched on a cell plate, and then cultured further. After 72 hours of culture, the growth of cells across the scratches was observed. Figure 18 It is evident that cells cultured in the metamaterial extract exhibited a larger growth area and density on the scratches compared to the control group, and also demonstrated a higher migration rate. Therefore, the bone repair metamaterial of this invention promotes the activity and proliferation of HUVEC cells.

[0125] Figure 19 This image shows the experimental results of vascular endothelial cell lumen formation using a bone repair material according to an embodiment of the present invention. HUVEC cells were digested and seeded on a specific culture medium, and after 6 hours of adding the material extract, the formation of tubular structures by endothelial cells was observed using an inverted microscope. Figure 19 As shown, the number of tubules formed by cells cultured in the metamaterial extract was greater than that in the control group. Therefore, the bone repair metamaterial of the present invention promotes the activity and proliferation behavior of HUVEC cells.

[0126] Those skilled in the art should understand that the above embodiments are merely for illustrating the present invention and are not intended to limit the scope of the invention. Those skilled in the art can make other changes or modifications based on the above disclosure, and these changes or modifications still fall within the scope of the present invention.

Claims

1. A method for manufacturing a bone repair material, characterized in that, The bone repair material is formed by a cell structure, the outline of which is a cube. The cube has two opposing surfaces and four side surfaces surrounding the two surfaces. The cell structure is formed by a plurality of first beams and second beams. Each surface has a first node located at the center of the surface and four third nodes located at the vertices of the cube. Each side surface has a second node located at the center of the side surface. The cube also has a fourth node located at the center of the cube. Each side is formed by two first beams, and in the same side, the apex of the arc of the two first beams is connected to the second node, and the two ends of each first beam are respectively connected to two third nodes on the same surface; Each of the surfaces is formed by two first beams, and in the same surface, the apex of the arc of the two first beams is connected to the first node, and the two ends of each first beam respectively form the third node; Each of the second nodes is connected to the first node via the second beam; The second nodes of two adjacent sides are connected by the second beam; The manufacturing method includes: Construct a first cell structure model, in which the first beam and the second beam of the first cell structure are both straight rods; The first beam and the second beam in the first cell structure model are replaced with at least a semi-circular arc rod to obtain the second cell structure model; in the second cell structure model, the first beam is a semi-circular arc first beam, and the arc of the second beam is a quarter-circular arc; The first beam and the second beam are formed using minimal surface structures to obtain the third cell structure model; The third cell structure model is spatially arrayed to obtain an array structure model; Based on the array structure model, an additive manufacturing process is used to produce bone repair materials.

2. The method for manufacturing bone repair material according to claim 1, characterized in that, The first beam and the second beam are formed using minimal surface structures to obtain the third cell structure model, including: The cube of the cell structure is divided into multiple sub-cubes, and each sub-cube is filled with a lattice of a minimal curved surface structure. The intersection of the lattice in each sub-cube with the first beam and the second beam of the cell structure is taken using Boolean operations.

3. The method for manufacturing bone repair material according to claim 2, characterized in that, The additive manufacturing process includes selective laser melting.

4. The method for manufacturing bone repair material according to claim 3, characterized in that, The selective laser melting process has a laser power of 130 W to 150 W, a powder layer thickness of 20 μm to 40 μm, and a hatch scanning spacing of 70 μm to 90 μm.

5. The method for manufacturing bone repair material according to claim 3, characterized in that, The scanning speed of the selective laser melting process is negatively correlated with the peak temperature of the austenitic phase transformation of the bone repair material.

6. The method for manufacturing bone repair material according to claim 3, characterized in that, The substrate for the selective laser melting process is a shape memory alloy.

7. The method for manufacturing bone repair material according to claim 6, characterized in that, The shape memory alloy includes one of copper-based shape memory alloys, iron-based shape memory alloys, and nickel-titanium-based shape memory alloys.

8. A bone repair material, characterized in that, It is prepared by the bone repair material manufacturing method according to any one of claims 1-7.

Images