A porous bone scaffold

Abstract

The application discloses a porous bone support which can improve the combination speed of the bone support and bone. The porous bone support comprises a basic support and a fixed support; the fixed support is connected in the basic support, and the bone connecting surface of the fixed support is flush with the bone connecting surface of the basic support.

Description

TECHNICAL FIELD

[0001] The present application relates to a porous bone scaffold. BACKGROUND

[0002] Bone defects caused by trauma, inflammation, tumors, etc. are one of the important reasons for causing functional loss and decline in quality of life in patients in clinic. Traditional treatment methods use bone grafting technology. Bone grafting technology has many defects, such as limited bone grafting from autologous bone, increased pain in the donor site, allogeneic bone grafting, slow bone healing, and immune rejection. Bone tissue engineering using porous bone scaffolds as a replacement has gradually developed.

[0003] The emergence of 3D printing technology provides a new method for the design and manufacture of tissue engineering artificial bone scaffolds. Compared with other bone tissue engineering scaffold preparation methods, 3D printing technology has the advantages of high precision, fast construction speed, and high spatial structure complexity, and can realize personalized design and preparation of the scaffold structure. In recent years, 3D printing technology has been widely used in the production of tissue engineering scaffolds, prosthetic implants, etc.

[0004] However, the 3D printed scaffolds currently used in clinical applications have a single pore structure, often simple repetition of the same pore size and channel structure, which can cause slow bone ingrowth in the later stage. In addition, the existing 3D printed porous scaffolds have a pore size of about 300-2000 μm, which is generally large, which can easily cause insufficient bone deposition and insufficient connection strength at the scaffold / bone interface, resulting in scaffold loosening. Therefore, the structure of the porous scaffold should be designed to fully utilize the advantage of 3D printing technology that can accurately control the internal structure to achieve better bone ingrowth effect. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a porous bone scaffold that can improve the bonding speed of the bone scaffold and the bone.

[0006] To solve the above technical problems, the embodiments of the present application adopt the following technical solutions:

[0007] A porous bone scaffold, comprising a base scaffold and a fixed scaffold; the fixed scaffold is connected inside the base scaffold, and the bone connecting surface of the fixed scaffold is flush with the bone connecting surface of the base scaffold.

[0008] As a preferred example, the base scaffold is a connected pore structure.

[0009] As a preferred example, the fixed scaffold is a connected pore structure.

[0010] As a preferred example, the equivalent diffusion coefficient of the base scaffold is greater than the equivalent diffusion coefficient of the fixed scaffold.

[0011] As a preferred example, the ratio of the equivalent diffusion coefficient of the base stent to the bulk diffusion coefficient of the liquid is greater than or equal to 0.3.

[0012] As a preferred example, the ratio of the equivalent diffusion coefficient of the fixed stent to the bulk diffusion coefficient of the liquid is less than or equal to 0.3.

[0013] As a preferred example, in the direction of bone ingrowth, the depth of the fixed stent is less than the depth of the base stent.

[0014] As a preferred example, the cross-sectional area of the fixed stent accounts for 10% to 80% of the total stent cross-sectional area.

[0015] As a preferred example, the cross-sectional area ratio of the fixed stent to the base stent is 10 to 50%.

[0016] As a preferred example, the fixed stent has a wall around it.

[0017] Compared with the prior art, the embodiments of the present application have the following beneficial effects:

[0018] 1. The combined pore structure porous metal stent of the present application changes the current situation of single 3D printing stent pore structure, can fully utilize the advantages of 3D printing technology, designs the internal pore structure of the stent according to the tissue engineering model, and provides the most ideal environment for growth factor transportation and cell migration and differentiation.

[0019] 2. The combined pore structure porous metal stent of the present application is provided with a stent structure with a complex diffusion field and a small equivalent diffusion coefficient at the stent connection, many in-vivo experiments have proved that cells are more likely to migrate inward and have a higher ingrowth depth in a stent with a smaller bending degree. The pore with a higher bending degree has a complex diffusion field, which can promote cell deposition at the pipe opening. Therefore, the design of the bending pore at the front section of the base stent is helpful for rapid bone tissue ingrowth and fixation in the early stage, and avoids stent loosening caused by insufficient connection strength.

[0020] 3. The combined pore structure porous metal stent of the present application adopts a structure with a large porosity in both main components, which can ensure that the overall stent has a large porosity, is conducive to the inward migration of stem cells and endothelial cells, promotes angiogenesis in the stent, and improves the bone ingrowth depth and deposition amount in the stent. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 is a structural schematic diagram of the embodiment of the present application;

[0022] Figure 2 is a partial sectional view of the embodiment of the present application;

[0023] Figure 3 is a simulation process flowchart for testing the embodiment of the present application;

[0024] Figure 4 Figure 1 is a schematic diagram of a method for measuring the equivalent diffusion coefficient of a porous bone scaffold according to an embodiment of the present application;

[0025] Figures 5(a) to 5(c) Figures 2(a) to 2(c) are three schematic diagrams of a fixed scaffold with an S-shaped structure according to an embodiment of the present application;

[0026] Figures 6(a) to 6(f) Figures 3(a) to 3(f) are six schematic diagrams of a fixed scaffold with a diamond structure according to an embodiment of the present application;

[0027] Figure 7(a) is a schematic diagram of the basic structure of a diamond cubic cell used in a fixed scaffold according to an embodiment of the present application;

[0028] Figure 7(b) is a schematic diagram of the basic structure of a diamond cubic cell in another direction according to an embodiment of the present application;

[0029] Figure 8 Figure 8 is a schematic diagram of one embodiment of a base scaffold with a truss structure according to an embodiment of the present application;

[0030] Figure 9(a) is a first schematic diagram of a base scaffold with a square hole structure according to an embodiment of the present application;

[0031] Figure 9(b) is a second schematic diagram of a base scaffold with a square hole structure according to an embodiment of the present application;

[0032] Figure 9(c) is a third schematic diagram of a base scaffold with a square hole structure according to an embodiment of the present application;

[0033] Figure 10 Figure 10 is a schematic diagram of another embodiment of a porous bone scaffold according to an embodiment of the present application;

[0034] Figure 11 Figure 11 is a graph of the percentage of bone deposition of a scaffold according to an embodiment of the present application and a conventional truss structure scaffold;

[0035] Figure 12 Figure 12 is a schematic diagram of a conventional truss structure bone scaffold;

[0036] Figure 13 Figure 13 is a schematic diagram of a wall-faced composite structure according to an embodiment of the present application;

[0037] Figure 14 Figure 14 is a schematic diagram of a wall-free composite structure according to an embodiment of the present application. DETAILED DESCRIPTION

[0038] Embodiments of the present application will be described in detail below with reference to the accompanying drawings. Here, only partial embodiments of the scaffold are given. It should be noted that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0039] As Figure 1 and Figure 2 shown, a porous bone scaffold of an embodiment of the present application comprises a base scaffold 1 and a fixation scaffold 2. The number of fixation scaffolds 2 can be multiple or one. The fixation scaffold 2 is connected inside the base scaffold 1. The bone connecting surface of the fixation scaffold 2 is flush with the bone connecting surface of the base scaffold 1. That is, the bone connecting surface of the fixation scaffold 2 and the bone connecting surface of the base scaffold 1 are on the same plane.

[0040] In the above porous bone scaffold, the size of the base scaffold 1 and the fixation scaffold 2 can be changed according to the requirements of the implantation site. The porous bone scaffold can be made of metal, bioceramics, polymer materials, composite materials, etc. In the porous bone scaffold of the above embodiment, the base scaffold 1 constitutes the main structure of the porous bone scaffold and plays a supporting role. The function of the fixation scaffold 2 is to make the bone grow in quickly and be fixed, avoiding the loosening of the bone scaffold.

[0041] When using the porous bone scaffold of the above embodiment, there are two parts of the fixation scaffold 2 and the base scaffold 1 on the bone ingrowth surface. The fixation scaffold 2 has a small equivalent diffusion coefficient. This structure makes the stem cells that have migrated into the fixation scaffold differentiate and mature faster and deposit into bone. At the same time, the base scaffold 1 ensures that the cells continue to migrate inward without being blocked at the bone connecting surface.

[0042] To realize the growth of bone in the porous bone scaffold, the base scaffold 1 is a connected pore structure.

[0043] The fixation scaffold 2 is a connected pore structure. The connected pore structure can have various forms, such as a truss structure, or a connected pore structure formed by periodically expanding structure units such as tetrahedron, hexahedron, dodecahedron, etc. The connected pore structure has good connectivity, which is beneficial to angiogenesis and nutrient transport, thereby achieving better bone ingrowth effect.

[0044] As a preferred example, the equivalent diffusion coefficient of the base scaffold 1 is greater than that of the fixation scaffold 2. The structure with a large equivalent diffusion coefficient is conducive to the inward migration of cells, and the base scaffold 1 adopts this structure to meet the requirement of continuous bone ingrowth of the scaffold. The fixation scaffold 2 adopts a structure with a small equivalent diffusion coefficient. When the cells migrate from outside the scaffold into the fixation scaffold 2, they can quickly differentiate and deposit, achieving the effect of early and rapid fixation.

[0045] Figure 4A schematic diagram of a method for measuring the equivalent diffusion coefficient of a porous bone scaffold is shown. For a three-dimensional porous scaffold with a height of L and the bone ingrowth direction being the vertical direction, it is assumed that the temperature and pressure remain unchanged, there is no flow of liquid in the scaffold, there is no source term, only solute diffusion is carried out, and the liquid in the scaffold only exchanges with the outside on the upper and lower two sides, and the vertical wall around the scaffold is a solid boundary. A solution with a certain concentration is loaded on the upper and lower boundaries of the scaffold, and the initial concentration of the upper boundary is C1 and the initial concentration of the lower boundary is C2. Due to the concentration difference, the solute in the pores of the scaffold will diffuse until a steady state is reached, i.e. the concentration of the solution at each point no longer changes. The equivalent diffusion coefficient D e As shown in equation (1):

[0046]

[0047] where N A represents the stable diffusion amount per unit area when diffusion reaches a steady state, with a unit of mol / (m 2 ·s); L represents the height of the bone scaffold, with a unit of m; ΔC represents the concentration difference of the solution loaded on both sides of the bone scaffold before the diffusion begins, with a unit of mol / m 3 .

[0048] Definition: The ratio of the equivalent diffusion coefficient D e of the liquid to the bulk diffusion coefficient D of the liquid is the specific diffusion coefficient k:

[0049]

[0050] As a preferred example, the ratio of the equivalent diffusion coefficient of the base scaffold 1 to the bulk diffusion coefficient of the liquid is greater than or equal to 0.3, i.e. the specific diffusion coefficient is greater than or equal to 0.3. The equivalent diffusion coefficient is the diffusion coefficient of a solute in a certain liquid and a scaffold composite medium. The value of the equivalent diffusion coefficient is related to the bulk diffusion coefficient and also related to the scaffold structure. However, in this embodiment, a parameter related only to the scaffold structure is needed, so the equivalent diffusion coefficient is divided by the bulk diffusion coefficient of the liquid to ensure that the ratio obtained is not affected by the type of liquid used in the measurement. Therefore, the liquid refers to the solution used to measure the equivalent diffusion coefficient, and the type of solution can be arbitrarily selected.

[0051] As a preferred example, the ratio of the equivalent diffusion coefficient of the fixed scaffold 2 to the bulk diffusion coefficient of the liquid is less than or equal to 0.3. As described above, the liquid refers to the solution used to measure the equivalent diffusion coefficient, and the type of solution can be arbitrarily selected.

[0052] As an embodiment, the fixed support 2 has a wall around it. In this way, in the direction perpendicular to the bone ingrowth direction, the base support 1 and the fixed support 2 do not communicate with each other, so that the two parts of the support have independent diffusion fields respectively, and the continuous wall can play a good fixing and connecting role. Of course, the fixed support 2 can also not be provided with a wall around it. In the direction perpendicular to the bone ingrowth direction, the base support 1 and the fixed support 2 communicate with each other. Whether or not to provide a wall, compared with the original single structure support, it is helpful for early rapid fixation. At the same time, compared with the wall-free, the early fixation effect is better. The bone deposition tests are carried out on the composite structure with wall (i.e. the combination of the fixed support and the base support), the composite structure without wall, and the truss structure of the bone support. The detailed parameters of the three kinds of bone supports are introduced in the following models. The bone deposition is tested at the 12th week, and the test results are shown in Figure 11 It can be seen from Figure 11 that the bone deposition effect of the structure with wall is better.

[0053] As a preferred example, in the bone ingrowth direction, the depth of the fixed support 2 is smaller than the depth of the base support 1. Because the bone is easy to deposit in the shallow position of the fixed support 2, the bone ingrowth depth in the fixed support 2 is very small, so if the fixed support 2 is too deep, the bone cannot grow full, which will cause internal cavities. The purpose of the fixed support 2 itself is early fixation, so the depth is a little smaller than that of the base support 1.

[0054] As a preferred example, on the end surface of the porous bone support in contact with the bone, the cross-sectional area of the fixed support 2 accounts for 10% to 80% of the cross-sectional area of the whole support, such as 10%, 25%, 40%, 50%, 75%, 80%, etc. The function of the fixed support 2 is to implant early fixation. If the cross-sectional area of the fixed support 2 is too large, it is easy to cause blockage, which is not conducive to the ingrowth of cells and blood vessels. If the cross-sectional area of the fixed support 2 is too small, the fixation effect is not obvious.

[0055] As a preferred example, the cross-sectional area ratio of the fixed support 2 to the base support 1 is 10% to 50%, such as 10%, 15%, 26%, 33%, 46%, 50%, etc.

[0056] In the above embodiment, the hole structure in the base support 1 has a small bending degree and a large equivalent diffusion coefficient, which provides main support in the outer layer and provides sufficient space for bone ingrowth. The hole structure in the fixed support 2 has a large bending degree and a small equivalent diffusion coefficient. In the direction perpendicular to the bone ingrowth direction, the two parts are connected by a tubular wall. Figure 2 It is a schematic view of the internal structure of the bone support. Figure 2 In order to clearly show the overall structure, Figure 2 the porosity of the support is appropriately increased.

[0057] The porous bone scaffold of the above embodiment overcomes the problems of slow scaffold / bone interface fixation and insufficient long-term ingrowth after implantation caused by the single pore structure of the existing 3D printed porous scaffold. The single pore structure is a structure composed of periodically arranged pores of the same shape and size. The bone scaffold of the embodiment includes a base scaffold 1 having a pore structure with a large equivalent diffusion coefficient and a fixation scaffold 2 having a pore structure with a small equivalent diffusion coefficient. The fixation scaffold 2 is located at the connection between the scaffold and the bone, and has a large bending degree of the pore structure, which can realize rapid bone tissue ingrowth and fixation in the early stage of implantation; the pores in the base scaffold 1 have a small degree of tortuosity, which is beneficial to angiogenesis and nutrient transport, and realizes a high bone ingrowth depth, thereby achieving a good bone healing effect.

[0058] The following simulation experiment verifies the excellent performance of the bone scaffold of the embodiment of the application.

[0059] The process of the simulation experiment is as follows:

[0060] S10 establishes a three-dimensional geometric model to determine the calculation region of the simulation model; imports a porous scaffold three-dimensional structure into the three-dimensional geometric model, and sets the scaffold region and the pore region for simulation calculation;

[0061] S20 calculates an immune regulation model based on the porous scaffold three-dimensional structure;

[0062] S30 sets simulation initial parameters; the initial parameters include simulation time;

[0063] S40 calculates a cytokine and growth factor model; calculates a cell life activity model; calculates a blood vessel growth model; and calculates an oxygen diffusion model;

[0064] S50 determines whether the simulation time end point is reached, if not, returns to step S40; if the simulation time end point is reached, the simulation is ended, and the simulation result is obtained.

[0065] In the above embodiment, the simulation model applied by the simulation method includes an immune regulation model, a cytokine and growth factor model, a cell life activity model, a blood vessel growth model, and an oxygen diffusion model.

[0066] In the simulation method of the above embodiment, each model is modeled and simulated from the mechanism of bone regeneration, and basically covers the main physiological processes of the bone ingrowth process. For example, the existing simulation method cannot explain the induction factors and principles of cells migrating from the outside into the scaffold and finally inducing bone formation, while the immune regulation model used by the application uses a basic mathematical form to represent this process. In addition, the application improves the calculation of the diffusion equation, so that the calculation results of the cytokine and growth factor model and the oxygen diffusion model are more accurate.

[0067] In the step S10, the porous scaffold three-dimensional structure includes a scaffold region and a pore region, the calculation region is divided into a plurality of unit cubes with equal edge length by grid division, the edge length of the unit cube is denoted as Δx, and the unit is μm; a three-dimensional rectangular coordinate system is established, and the position of each unit cube in the calculation region is represented by three-dimensional coordinates (x, y, z), wherein x, y and z represent the coordinates of the center point of the unit cube on the three-dimensional rectangular coordinate system. According to the scaffold structure, each unit cube in the calculation region is marked as a pore or a scaffold. This process uses a discretization method, on the one hand, the computer program itself needs to be discretized when calculating the continuous diffusion equation, on the other hand, the discrete grid model can better reflect the interaction between cells and microenvironment and accurately describe the complex biological process by simulating cell activity and angiogenesis.

[0068] In the step S20, the immune regulation model (1) is established according to formula (1):

[0069] G0=k·d formula (1)

[0070] Wherein, G0=G0(d), G0 represents the cytokine concentration at the initial moment, the distance between the scaffold surface and the connecting surface of the scaffold and the bone is d, k represents the proportion coefficient, and d represents the distance from the connecting surface of the scaffold and the bone.

[0071] The migration of cells into the scaffold is induced by the concentration gradient formed by the release of cytokines by immune cells. After the occurrence of bone defects, due to inflammatory reactions, immune cells such as neutrophils and macrophages gather at the wound site. The rough surface of the scaffold helps to promote the polarization of M2 macrophages, and M2 macrophages will adhere to the inner surface of the scaffold and secrete cytokines such as BMP2. On the inner surface of the scaffold, the number of M2 macrophages is proportional to the distance from each position to the connecting surface. The release amount of cytokines is proportional to the number of macrophages. This part describes the principle of immune regulation with a simple mathematical model, which is simple to calculate and can well reflect the process of immune regulation.

[0072] In the step S30, the initial parameters further include: the initial oxygen concentration of the pore region, the number of stem cells and endothelial cells at the edge of the scaffold, the oxygen diffusion coefficient of the pore region, the growth factor diffusion coefficient of the pore region, and the time step.

[0073] In the step S40, the cytokine and growth factor model (2) is shown in formula (2):

[0074]

[0075] Wherein, G=G(x, y, z, t), G represents the growth factor concentration at (x, y, z) in the three-dimensional rectangular coordinate system at t, D G represents the diffusion coefficient of the growth factor, dG represents the degradation rate of growth factors, f = f(x, y, z, t), f represents the generation amount at (x, y, z) in the three-dimensional rectangular coordinate system at t. f has various forms according to the source of growth factors in the scaffold. For example, if a growth factor coating is coated on the inner wall of the scaffold and is released at a constant rate, f can be represented as a constant; if the release amount of growth factors decreases over time, f can be represented as a function of t, such as f = ae 1 / bt (a, b are constants greater than 0).

[0076] The calculation region of the above diffusion equation is the pore region, and does not include the solid scaffold region, and the calculation region is relatively accurate.

[0077] In the step S40, the cell life activity model includes cell migration, proliferation, differentiation, apoptosis, and secretion of hypoxia-inducible factors.

[0078] The migration probability of the cell in a certain direction is shown in formula (3):

[0079]

[0080] wherein, represents the probability of cell migration in the i direction, [O2] represents the oxygen concentration, [G] represents the growth factor concentration, represents the six direction vectors of up, down, left, right, front, and back, n represents the proportion factor of growth factors and oxygen to the guided cell migration, n is a positive integer; the migration probability of the cell at rest is defined as the average of the migration probabilities in all directions.

[0081] The cell proliferation rate and differentiation rate are related to the cell type, and for the same cell, the differentiation rate and proliferation rate are constants. A mesenchymal stem cell will gradually differentiate into a pre-osteoblast and a mature osteoblast over time, and the mature osteoblast will synthesize and secrete bone organic matter within q1 days (for example, 4 days), and will bury itself in the bone organic matter to become a bone cell. The newly formed organic matter is then combined with inorganic calcium, phosphorus, and other ions to deposit and mineralize, and after q2 days, for example, 30-60 days, new bone is formed. The newly formed bone is loose bone, and capillaries can grow into it.

[0082] The apoptosis model of the cell is shown in formula:

[0083]

[0084] wherein, p apop represents the average apoptosis probability of mesenchymal stem cells, pre-osteoblasts, and mature osteoblasts, [O2] represents the oxygen concentration, [O2] ave represents the average oxygen concentration of the interstitial fluid; represents a correction coefficient.

[0085] When the oxygen concentration of the environment where the cell is located is less than the oxygen threshold value, the cell directly undergoes apoptosis; when the oxygen concentration of the environment where the cell is located is relatively low but not less than the oxygen threshold value, the cell secretes hypoxia-inducible factor HIF-1 to promote the generation of vascular endothelial growth factor VEGF, induces the growth of blood vessels and provides oxygen, and the model is shown in formula (5):

[0086]

[0087] wherein [VEGF] represents the VEGF concentration, [HIF1-dimer N ] represents the HIF-1 dimer concentration, and vm represents the reaction rate of the HIF-1 dimer activating the generation of VEGF, and kp represents a regulation coefficient.

[0088] In the step S40, the blood vessel growth model includes migration, branching, fusion and sprouting.

[0089] Based on the chemotaxis of endothelial cells to the concentration gradient of vascular endothelial growth factor, the migration model of vascular endothelial cells is shown in formula (6):

[0090]

[0091] wherein [V] represents the VEGF concentration, represents the six directions of up, down, left, right, front and back; when the endothelial cell remains stationary, the probability of the endothelial cell when stationary is defined as the average of the probabilities of migration in each direction.

[0092] The blood vessels have a probability of branching; the blood vessel sprouts mature to a certain extent, and there is enough space around the blood vessel sprouts, so that branching can occur; it is assumed that the blood vessel branching only occurs at the top endothelial cell.

[0093] In the model, the blood vessel sprouts on different blood vessels randomly move and have a probability of collision; when two blood vessels collide, blood vessel fusion occurs; when two blood vessel sprouts collide, the two blood vessels are combined into one to continue growing. When a blood vessel sprout collides with an existing blood vessel network, the blood vessel sprout stops growing.

[0094] Sprouting refers to the fact that when capillary blood vessels are induced by vascular endothelial growth factor VEGF, there is a probability that new sprouts will be generated from the existing capillary network, and the new sprouts, like other blood vessel sprouts, guide the formation of a new blood vessel.

[0095] As an example, the migration speed of the blood vessel sprout is about 20 μm / h, so in each day of simulation, all activities of the blood vessel sprout are performed 20*24 / Δx times. Δx represents the edge length of the unit cube.

[0096] Compared with the continuous model, the embodiment simulates the angiogenesis by using the discrete grid model, can obtain a more real capillary grid, and can reflect the fusion, branching and other behaviors in the capillary growth process.

[0097] The oxygen diffusion model is shown as formula (7):

[0098]

[0099] O2 = O2 (x, y, z, t) represents the oxygen concentration at (x, y, z) in a three-dimensional rectangular coordinate system at t time, represents the oxygen diffusion coefficient, represents the oxygen permeability of blood vessels, represents the blood oxygen concentration, represents the cell oxygen consumption rate; when there is a blood vessel at (x, y, z) at t time, χ ves = χ ves (x, y, z, t) = 1, otherwise χ ves = χ ves (x, y, z, t) = 0. represents the cell oxygen consumption rate; when there is a cell at (x, y, z) at t time, χ cell = χ cell (x, y, z, t) = 1, otherwise χ cell = χ cell (x, y, z, t) = 0.

[0100] The calculation area of the diffusion equation is the hole area, and the scaffold area is not included, and the calculation area is accurate.

[0101] The above calculation model describes the processes of immune cell regulation, cell activity, growth factor diffusion, angiogenesis and oxygen transport in bone reconstruction, and the simulation results are consistent with the animal experiment results.

[0102] The bone scaffold of the embodiment and the existing single-hole structure scaffold are input into the above model for simulation calculation. In this experiment, the bone scaffold A is the existing single-hole structure scaffold, and the bone scaffold B and the bone scaffold C are the bone scaffolds with the structure of the embodiment.

[0103] The overall shape of the bone scaffold A, the bone scaffold B and the bone scaffold C is a cylindrical shape with a bottom diameter of 1.5mm and a height of 3mm. Among them,

[0104] The bone scaffold A adopts a truss structure, as shown in Figure 12 The truss structure is periodically repeated by octahedral units, the support rod of the bone scaffold is about 90μm in diameter, the hole diameter is about 600μm, and the specific diffusion coefficient is 0.92 (the same as the structure shown in FIG. 9).

[0105] The basic scaffold structure of the bone scaffold B and the bone scaffold C is the same as that of the bone scaffold A, and the fixed scaffold is located at the center of the upper surface of the basic scaffold. The fixed scaffold of the bone scaffold B and the bone scaffold C has a cylindrical shape with a bottom diameter of 600 μm and a height of 600 μm, and has a diamond cubic crystal structure, in which the distance between the vertices of the regular tetrahedron is about 156 μm, the diameter of the support rod is about 110 μm, and the pore size is about 200 μm. The diffusion coefficient is 0.22 (the same as the structure shown in Figure 6f ).

[0106] The bone scaffold B has a bone scaffold structure in which a wall surface is arranged around the fixed scaffold, as shown in Figure 13 . The bone scaffold C has a bone scaffold structure in which no wall surface is arranged around the fixed scaffold, as shown in Figure 14 . The basic scaffold and the fixed scaffold of the bone scaffold B and the bone scaffold C have the same size and structure, and the only difference is whether the basic scaffold and the fixed scaffold have a connecting wall surface in the direction perpendicular to the bone ingrowth.

[0107] The results of the model calculation are shown in Figure 11 . As can be seen from Figure 11 , compared with the single-hole structure scaffold, the bone scaffold of the embodiment of the present application has a larger deposition amount at the pipe opening in the early stage of implantation, and a deeper ingrowth depth in the later stage. This shows that the bone scaffold with the composite structure of the embodiment has the effect of rapid fixation, and has a better bone healing effect.

[0108] The following is an example of the bone scaffold structure of the embodiment of the present application.

[0109] Example 1: Three embodiments of the fixed scaffold with an S-shaped structure, as shown in Figures 5(a)-5(c) . In the figure, the gray part is a hole, and the remaining blank part is a scaffold. The total pore size (the maximum pore size in the ingrowth direction) of the three scaffolds is 600 μm. The minimum pore size in the ingrowth direction of the scaffold shown in Fig. 5(a) is 60 μm, and the diffusion coefficient is 0.03. The minimum pore size in the ingrowth direction of the scaffold shown in Fig. 5(b) is 240 μm, and the diffusion coefficient is 0.07. The minimum pore size in the ingrowth direction of the scaffold shown in Fig. 5(c) is 360 μm, and the diffusion coefficient is 0.34.

[0110] Example 2: Six embodiments of the fixed scaffold with a diamond structure, as shown in Figures 6(a)-6(f) . In the figure, the gray part is a scaffold, and the remaining blank part is a hole. Figures 6(a)-6(c) The basic structures are the same as those of Figures 6(d)-6(f) , and the directions are different by 45°. Figure 6(a) and 6(d)The distance between the vertices of the regular tetrahedron is about 208 μm, the diameter of the support rod of the scaffold is about 60 μm, and the aperture is about 340 μm. The specific diffusion coefficient of the structure in Fig. 6(a) is 0.86, and the specific diffusion coefficient of the structure in Fig. 6(d) is 0.89. The distance between the vertices of the regular tetrahedron in Fig. 6(b) and Fig. 6(e) is about 156 μm, the diameter of the support rod of the scaffold is about 60 μm, and the aperture is about 240 μm. The specific diffusion coefficient of the structure in Fig. 6(b) is 0.65, and the specific diffusion coefficient of the structure in Fig. 6(e) is 0.70. The distance between the vertices of the regular tetrahedron in Fig. 6(c) and Fig. 6(f) is about 156 μm, the diameter of the support rod of the scaffold is about 110 μm, and the aperture is about 200 μm. The specific diffusion coefficient of the structure in Fig. 6(c) is 0.11, and the specific diffusion coefficient of the structure in Fig. 6(f) is 0.22.

[0111] The basic structure of the diamond cell structure is shown in Fig. 7. Fig. 7(a) is the same as Fig. 7(b), and Fig. 7(a) is rotated by 45° in the vertical direction to obtain the structure of Fig. 7(b). Each vertex in the diamond cell structure is connected to four support rods, and the four vertices adjacent to the vertex form a regular tetrahedron, so the angle between the two support rods passing through any vertex is 109.5°.

[0112] Example 4: Figure 8 is an embodiment of the basic scaffold described in the present application as a truss structure. The gray part is the scaffold, and the remaining blank part is the hole. The truss structure is periodically repeated by octahedral units, the diameter of the support rod is about 90 μm, the aperture is about 600 μm, and the specific diffusion coefficient is 0.92.

[0113] Example 5: Figures 9(a)-9(c) is three embodiments of the basic scaffold described in the present application as a square hole structure. The gray part is the scaffold, and the remaining blank part is the hole. The scaffold hole diameter of Fig. 9(a) is 300 μm, the scaffold diameter is 120 μm, the minimum hole diameter is 180 μm, and the specific diffusion coefficient is 1.23. The scaffold hole diameter of Fig. 9(b) is 300 μm, the scaffold diameter is 60 μm, the minimum hole diameter is 240 μm, and the specific diffusion coefficient is 1.33. The scaffold hole diameter of Fig. 9(c) is 450 μm, the scaffold diameter is 120 μm, the minimum hole diameter is 330 μm, and the specific diffusion coefficient is 1.29.

[0114] In the above embodiments, examples 1, 2 and 3 are fixed scaffolds, and examples 4 and 5 are basic scaffolds. The three fixed scaffolds and two basic scaffolds can be combined in any way as long as the fixed scaffold 2 is connected inside the basic scaffold 1, and the bone connecting surface of the fixed scaffold 2 is flush with the bone connecting surface of the basic scaffold 1.

[0115] Figure 10Another structure of the embodiment of the present application is shown. In this holder, the base holder 1 is cuboid in shape, in which four fixed holders 2 are inlaid, respectively located on the four corners of the upper surface of the base holder 1. This structure can be used for the implantation site with higher fixation requirement in the early stage.

[0116] The above shows and describes the basic principles, main features and advantages of the present application. It should be understood by those skilled in the art that the present application is not limited by the above specific embodiments, and the above specific embodiments and the description in the specification are only for further illustration of the principles of the present application. Without departing from the spirit and scope of the present application, various changes and improvements can be made to the present application, and these changes and improvements all fall within the scope of the claimed present application. The scope of the present application is defined by the claims and their equivalents.

Claims

1. A porous bone scaffold, characterized in that, The base support (1) and the fixed support (2) are included; the fixed support (2) is connected inside the base support (1), and the bone connecting surface of the fixed support (2) is flush with the bone connecting surface of the base support (1); the equivalent diffusion coefficient of the base support (1) is greater than the equivalent diffusion coefficient of the fixed support (2); The method for measuring the equivalent diffusion coefficient of a porous bone scaffold comprises: for a three-dimensional porous scaffold with a height of L and a bone ingrowth direction being a vertical direction, assuming that temperature and pressure remain unchanged, liquid does not flow in the scaffold, there is no source term, only solute diffusion is performed, and liquid in the scaffold only exchanges substances with the outside at the upper and lower two surfaces, and the vertical wall surface around the scaffold is a solid boundary; a solution with a certain concentration is loaded at the upper and lower boundaries of the scaffold, and the initial concentration of the upper boundary is C1, and the initial concentration of the lower boundary is C2; due to the concentration difference, the solute in the pores in the scaffold will diffuse until a stable state is reached, that is, the solution concentration at each place no longer changes; the equivalent diffusion coefficient D e As shown in formula (1): where N A represents the steady-state diffusion amount per unit area, unit: mol / (m 2 ·s); L represents the height of the bone scaffold, unit: m; ΔC represents the concentration difference of the solution loaded on both sides of the bone scaffold before the diffusion begins, unit: mol / m 3 ; the equivalent diffusion coefficient is the diffusion coefficient of the solute in the composite medium of the liquid and the scaffold.

2. The porous bone scaffold of claim 1, wherein, The base support (1) is a communicating hole structure.

3. The porous bone scaffold of claim 1 or 2, wherein, The fixed support (2) is a communicating hole structure.

4. The porous bone scaffold of claim 1, wherein, The ratio of the equivalent diffusion coefficient of the base support (1) to the bulk diffusion coefficient of the liquid is greater than or equal to 0.

3.

5. The porous bone scaffold of claim 1, wherein, The ratio of the equivalent diffusion coefficient of the fixed support (2) to the bulk diffusion coefficient of the liquid is less than or equal to 0.

3.

6. The porous bone scaffold of claim 1, wherein, In the direction of bone ingrowth, the depth of the fixed support (2) is less than the depth of the base support (1).

7. The porous bone scaffold of claim 1, wherein, The cross-sectional area of the fixed support (2) accounts for 10-80% of the cross-sectional area of the whole support.

8. The porous bone scaffold of claim 7, wherein, The cross-sectional area ratio of the fixed support (2) to the base support (1) is 10-50%.

9. The porous bone scaffold of claim 1, wherein, The fixed support (2) has a wall surface around it.

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