A cellular structure, metamaterial for bone repair

Abstract

The application provides a cell structure and a metamaterial for bone repair, and relates to the technical field of metamaterials. The cell structure has a cubic profile, two opposite surfaces, four side surfaces arranged between the two surfaces, each surface has a first node at the center of the surface and four third nodes at the vertices of the cube, each side surface has a second node at the center of the side surface, and the cube has a fourth node at the center of the cube; each side surface is formed by two first beams, in the same side surface, the arch tops of the two first beams are connected to the second node, and the two ends of each first beam are connected to two third nodes of the same surface; each surface is formed by two first beams, in the same surface, the arch tops of the two first beams are connected to the first node, and the two ends of each first beam form a third node; and each second node is connected to the first node through a second beam. The metamaterial can meet the adaptation of a bone implant object with complex requirements.

Description

Technical Field

[0001] This invention relates to the field of metamaterials technology, and more particularly to a cellular structure and metamaterial for bone repair. Background Technology

[0002] Due to traffic accidents and orthopedic diseases, a large number of patients face bone defects. Simultaneously, bone aging, osteoporosis, and even necrosis inevitably lead to bone defects. When bone defects exceed a critical threshold, osteoblast repair becomes insufficient, especially in cases of severe fractures, diseases, and bone aging. In these situations, bone defects struggle to heal on their own, making bone transplantation unavoidable. Using bone implants to replace damaged or missing bone is crucial. After implantation, bone implants should not repel the body; instead, they should promote bone and blood vessel growth, thus facilitating bone defect repair.

[0003] Among related technologies, bone implants struggle to meet the complex requirements of practical applications. Summary of the Invention

[0004] The purpose of this invention is to provide a cellular structure and metamaterial for bone repair, in order to solve the technical problem that bone implants are difficult to meet the complex requirements of practical applications.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides a cell structure for bone repair, the cell structure having a cube 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.

[0007] The cell structure also includes multiple semi-circular first beams and circular second beams.

[0008] 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;

[0009] 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;

[0010] Each of the second nodes is connected to the first node via the second beam;

[0011] The second nodes of two adjacent sides are connected by the second beam;

[0012] Both the first beam and the second beam are formed by minimal curved surface structures.

[0013] According to at least one embodiment of the present invention, the arc shape of the second beam is a quarter-circle arc.

[0014] 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.

[0015] 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.

[0016] 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.

[0017] 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.

[0018] According to at least one embodiment of the present invention, the cross-section of the second beam is circular.

[0019] In a second aspect, the present invention also provides a metamaterial for bone repair, which is formed by an array of multiple cell structures, wherein the cell structure is the cell structure described in the first aspect;

[0020] In the two fitted cell structures, the two second beams corresponding to different cell structures are arranged in a semi-circular shape.

[0021] According to at least one embodiment of the present invention, the stiffness, porosity, and pore size of the metamaterial are decoupled.

[0022] 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,

[0023] The size of the Gyroid unit cell is negatively correlated with the stiffness of the metamaterial.

[0024] 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.

[0025] The cellular structure of this exemplary embodiment is an overall 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 apexes of the two first beams are connected to a second node (the center point of the face of that side surface), and the connecting segments of each first beam are respectively connected to two third nodes on the same surface. On the same surface, the arc apexes of the two first beams are connected to a first node (the center point of the face of that surface), and the two ends of each first beam respectively form a third node (the vertex 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. This cellular structure is arranged in an atomic face-centered cubic pattern and has the characteristic of high specific strength. Compared to setting the first beam and the second beam as straight rods, setting the first beam as a semi-circular arc structure and the second beam as a circular arc structure further improves the overall stiffness and strength of this cellular structure.

[0026] 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. Attached Figure Description

[0027] 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.

[0028] Figure 1 This is an isometric structural diagram of a cell structure according to an embodiment of the present invention;

[0029] Figure 2 This is a front view schematic diagram of the cell structure according to an embodiment of the present invention;

[0030] Figure 3 This is a schematic diagram illustrating the design principle of the cell structure according to an embodiment of the present invention;

[0031] Figure 4 These are stress-strain curves before and after macroscopic optimization of the cell structure according to an embodiment of the present invention;

[0032] Figure 5 These are stress-strain curves of metamaterials with different rod diameters according to embodiments of the present invention;

[0033] Figure 6 These are stress-strain curves of metamaterials with different wall thicknesses according to embodiments of the present invention;

[0034] Figure 7 These are stress-strain curves of metamaterials with different microscopic cell sizes according to embodiments of the present invention;

[0035] Figure 8 These are the stiffness values ​​of metamaterials with different geometric parameters according to embodiments of the present invention;

[0036] 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.

[0037] 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;

[0038] 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.

[0039] 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

[0040] 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.

[0041] 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.

[0042] Bone transplantation is one approach to repairing bone defects. However, existing bone implants cannot adjust the stiffness and pore size of metamaterials according to the bone modulus of the implantation site and the optimal pore size for bone cell growth, making it difficult to meet the complex requirements of actual bone transplantation.

[0043] To address the aforementioned issues, the exemplary embodiment of this invention provides a cell structure in which the macroscopic cell structure adopts a multi-biomimetic strategy combining two biomimetic structures. By improving upon the Octet lattice structure and incorporating the U-shaped arch from the tortoise shell structure, the beams forming the Octet lattice structure are formed using a biocompatible minimal curved surface structure. This allows for the decoupling of the metamaterial's stiffness, pore size, and porosity, enabling separate control to ensure the metamaterial adapts to the bone at the implantation site and possesses biocompatibility.

[0044] 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 2 As shown, in the cellular structure provided by the exemplary embodiment of the present invention, the outline of the cellular structure is a cubic frame structure. 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. In the same side 20, the arc apex 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 of the same surface 10; each surface 10 is formed by two first beams 41, and the arc apex 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.

[0045] 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.

[0046] 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.

[0047] Figure 3 This is a schematic diagram illustrating the design principle of the cell structure according to an embodiment of the present invention. Figure 3 As 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 cubic frame structure, 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.

[0048] 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.

[0049] When the second beam 42 is a quarter-circle arc rod, after the cell structure forms a metamaterial, the two adjacent cell structures are at the second node 32 on the side 20. Since the openings of the second beam 42 are all facing 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 are set in a U-shaped arch, so that the structure forming the metamaterial is a U-shaped arch structure both on the surface and inside, thereby increasing the stiffness and strength of the metamaterial.

[0050] like Figure 3 As shown, after optimizing the macroscopic scale of the cell structure, the microscopic scale of the cell structure is also optimized. For example, the beams are formed using minimal curved surface structures to give the cell structure excellent biocompatibility.

[0051] 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.

[0052] For example, in the exemplary embodiment of the present invention, the first beam 41 and the second beam 42 in the cell structure are both formed by a Gyroid three-period minimal surface structure. When this Gyroid three-period minimal surface structure is fused with the macroscopic cell, the size of the macroscopic cube and the size of the microscopic sub-cube are selected. The macroscopic cube contains multiple microscopic virtual sub-cubes, which are filled with a Gyroid lattice. The microscopic structure is then filled into the macroscopic cell structure, and an intersection operation is performed to form the cell 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.

[0053] 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 shape.

[0054] Metamaterials used for bone repair are 3D printed in one piece. The materials of metamaterials can be various alloys, such as magnesium alloys, zinc alloys, aluminum alloys, titanium alloys, stainless steel, copper alloys, cobalt-based alloys, zirconium-based alloys, etc.

[0055] 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.

[0056] For example, using a macroscopic cubic unit cell with a length L = 20 mm, various metamaterial samples were printed by changing the macroscopic geometric parameters of the rod diameter R, the microscopic geometric parameters of the Gyroid unit cell size c, and the 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.

[0057] Table 1 Metamaterial samples under different geometric parameters

[0058]

[0059] 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.

[0060] 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.

[0061] 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.

[0062] 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.

[0063] Figure 7These 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.

[0064] Figure 8 These are the stiffness values ​​of metamaterials with different geometric parameters according to embodiments of the present invention. For example... Figure 8 As 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, by separately adjusting the pore size, stiffness, and porosity within a wide range, the most suitable pore size can be provided 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.

[0065] 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.

[0066] 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.

[0067] 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.

[0068] 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.

[0069] 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.

[0070] All experiments included a control group that was cultured without the extract.

[0071] 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.

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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.

[0076] 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 cellular structure for bone repair, characterized in that, The outline of the cell structure is a cube, the cube has two opposing surfaces and four side surfaces surrounding the two surfaces, 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, and the cube also has a fourth node located at the center of the cube. The cell structure also includes multiple semi-circular first beams and circular second beams. 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 second beam has a quarter-circle arc shape; 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; The apex of the arc of each of the second beams connecting the second nodes of two adjacent sides is close to the fourth node; The cross-section of the second beam is circular.

2. A metamaterial for bone repair, characterized in that, It is formed by an array of multiple cell structures, wherein the cell structure is the cell structure described in claim 1; In the two fitted cell structures, the two second beams corresponding to different cell structures are arranged in a semi-circular shape.

3. The metamaterial according to claim 2, characterized in that, The diameter of the second beam and the wall thickness of the Gyroid unit cell are positively correlated with the stiffness of the metamaterial.

4. The metamaterial according to claim 3, characterized in that, The size of the Gyroid unit cell is negatively correlated with the stiffness of the metamaterial.

5. The metamaterial according to claim 2, characterized in that, The porosity of the metamaterial ranges from 50% to 90%.

6. The metamaterial according to claim 2, characterized in that, The diameter of the micropores in the metamaterial ranges from 150 μm to 700 μm.

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