Porous double-gradient bone scaffold with shape memory effect and preparation method thereof

Abstract

The invention belongs to the technical field of biological materials, and particularly discloses a porous double-gradient bone scaffold with a shape memory effect and a preparation method thereof.The porous double-gradient bone scaffold comprises a porous lattice structure which is made of a memory material and provided with a plurality of structural layers, internal pores of the porous lattice structure are communicated, and the shape memory effect of the porous lattice structure is improved. And the porosity of the porous lattice structure is in double-gradient change. The bone scaffold is extremely good in matching degree with bones, can be well matched with the porosity and the arrangement mode of cortical bones and cancellous bones of the human body, has a shape memory effect, can be compressed before being implanted into the body of a patient, effectively reduces the size of the scaffold, and is suitable for popularization and application. In the operation process, only a small wound is opened at a defect part, shape recovery occurs after the device is implanted into a human body in the operation, and the size is increased to a preset shape matched with the defect part before compression and is completely matched with the defect part.

Description

Technical Field

[0001] The present application belongs to the field of biomaterial technology, and more specifically, relates to a porous dual-gradient bone scaffold with shape memory effect and a preparation method thereof. Background Art

[0002] Bones are the main carrier of all human activities. Population aging, trauma, infection, tumors and other factors can cause bone tissue defects. Bones have a certain repair function and can repair minor trauma, but when the size of bone defects exceeds a certain value, artificial intervention is required to implant stents for repair.

[0003] In the related technology, bone tissue is mainly divided into two parts: cortical bone and cancellous bone. The cortical bone tissue is dense, has high strength and density, and bears the main load-bearing role; cancellous bone is highly porous and has a high porosity. It accommodates blood vessels, bone cells, etc., and is a transmission channel for nutrients and waste. The porosity and mechanical properties of cortical bone and cancellous bone are different. At present, the traditional artificial synthetic material scaffolds used in clinical practice, such as ceramic materials and traditional medical metal material scaffolds, are large in size and have a single structural design. During the implantation process, a large wound needs to be opened at the defect site of the human body, causing greater damage to the human body. In addition, the implanted bone scaffold does not match the bone well, and is in urgent need of improvement. Summary of the invention

[0004] In response to the defects of the prior art or the need for improvement, the present application provides a porous dual-gradient bone scaffold with shape memory effect and a preparation method thereof, aiming to solve the problems of poor matching between the existing bone scaffold and the bone and large surgical incision.

[0005] The present application provides a porous dual-gradient bone scaffold with shape memory effect, comprising a porous lattice structure with multiple structural layers made of memory material, the internal pores of the porous lattice structure are connected, and the porosity of the porous lattice structure presents a dual gradient change.

[0006] Through the above technical solutions conceived by the present application, compared with the prior art, the present bone scaffold adopts a porous lattice structure with dual gradient changes, which can well adapt to the porosity and arrangement of human cortical bone and cancellous bone, can adapt to the human body environment and ensure the transmission of human bone nutrients and the repair of defective parts, and promote the growth and repair of defective parts. In addition, the present bone scaffold has a shape memory effect, can be compressed before implantation in the patient's body, effectively reducing the size of the scaffold, and only a small wound can be opened at the defective part during the operation. After implantation in the human body during the operation, the shape is restored and the size increases to the shape of the defective part predetermined before compression, and it completely matches the defective part. This design can effectively reduce the surgical wound by utilizing the shape memory effect, and match the irregular defective part after implantation, and stress stimulates bone tissue repair.

[0007] As a further preference, the unit cell of the porous lattice structure is a five-mode superstructure composed of double cone rods, wherein the middle diameter of the double cone rods is larger than the diameters at both ends.

[0008] As a further preference, the matrix structure of the five-mode superstructure is a diamond lattice structure.

[0009] As a further preference, the diameters of both ends of the double-cone rod are 0.17mm-0.23mm, and the middle diameter is 0.25mm-0.4mm.

[0010] As a further preference, in the porous lattice structure, the double cone rods in different layers have the same diameter at both ends and different diameters in the middle.

[0011] As a further preference, the porosity of the porous lattice structure gradually increases from both ends to the middle.

[0012] As further preferred, the memory material is NiTi shape memory alloy powder.

[0013] As further preferred, the mass fraction of Ni element in the NiTi shape memory alloy powder is 55.75%, and the powder particle size is 15 μm-53 μm.

[0014] A preparation method provided in the second aspect of the present application adopts the following technical solution: A preparation method for preparing any one of the porous dual-gradient bone scaffolds with shape memory effect described in the first aspect, comprising the following steps: Based on the known characteristics of bone structure, a porous lattice structure model with interconnected internal pores and a porosity showing a double gradient change was constructed. Slice the porous lattice structure model to obtain three-dimensional slice data; Using memory material as raw material, porous dual-gradient bone scaffolds with shape memory effect are prepared by printing layer by layer based on three-dimensional slice data.

[0015] As further preferred, the step of constructing the porous lattice structure model includes: Construct a five-mode superstructure model consisting of double-conical rods; Based on the five-mode superstructure model, a porous lattice structure layer model is constructed; Based on the known bone structure characteristics, the diameters of the double cone rods in the porous lattice structure layer model are set to obtain multiple porous lattice structure layer models with different porosities; The porous lattice structure layer models with different porosities are combined to form a porous lattice structure model with a porosity showing a double gradient change.

[0016] In general, the above technical solutions conceived by this application have the following technical advantages compared with the prior art: 1. The porous double-gradient bone scaffold can imitate the porosity and arrangement of human cortical bone and cancellous bone. By adjusting the middle diameter and the diameters at both ends of the single-cell double-cone rod structure, the porosity of the porous lattice structure can be controlled. Then, a gradient pore distribution structure is set according to the internal structure of human bones. The double-gradient pore structure is constructed by overlapping the layers and the internal pores are connected. This design enables the bone scaffold to adapt to the human body environment and ensure the transmission of human bone nutrients and the repair of defective parts, thereby promoting the growth and repair of defective parts.

[0017] 2. The porous dual-gradient bone scaffold has a shape memory effect and can be compressed in a low-temperature environment in vitro, effectively reducing the size of the scaffold. During the operation, only a small incision can be made at the defect site. After being implanted in the human body during the operation, the temperature rises to the human body temperature, and a phase transition occurs inside the scaffold, so the shape is restored, and the size increases to the shape of the defect site that is predetermined before compression, and completely matches the defect site. Under this design, the surgical incision can be effectively reduced by utilizing the shape memory effect, and after implantation, it matches the irregular defect site, and stress stimulates bone tissue repair.

[0018] 3. This design controls the diameters of both ends of the double-cone rods between different layers to remain unchanged, so as to ensure the tight connection between the layers, thereby achieving structural stability and pore penetration of the porous lattice structure; and by adjusting the middle diameters of the double-cone rods in different layers, the middle diameters of the double-cone rods in each layer gradually decrease from the upper and lower layers to the middle layer, so that the porosity of the porous lattice structure presents a double gradient distribution that gradually increases from the top to the bottom to the middle. The porous double-gradient bone scaffold under this design can match the bone structure and has good biocompatibility and mechanical properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a schematic diagram of the overall structure of a porous dual-gradient bone scaffold with shape memory effect provided in an embodiment of the present application; Figure 2 This is a physical display diagram of a porous double-gradient bone scaffold provided in an embodiment of the present application; Figure 3 is a schematic diagram of a five-mode superstructure provided in an embodiment of the present application; Figure 4 This is a front view of a porous double-gradient bone scaffold provided in an embodiment of the present application; Figure 5 This is a performance diagram of a NiTi alloy for a porous double-gradient bone scaffold provided in an embodiment of the present application; Figure 6 This is a graph showing the shape recovery rate change of a porous dual-gradient bone scaffold with shape memory effect after compression provided by an embodiment of the present application; Figure 7 This is a flow chart for preparing a porous dual-gradient bone scaffold provided in an embodiment of the present application. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solution and advantages of the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0021] The following is combined with Figure 1-Figure 7 This application is described in further detail.

[0022] The present application embodiment discloses a porous dual-gradient bone scaffold with shape memory effect. Figure 1-Figure 4 The porous dual-gradient bone scaffold with shape memory effect includes a porous lattice structure with multiple structural layers made of memory material, the internal pores of the porous lattice structure are connected, and the porosity of the porous lattice structure presents a dual gradient change.

[0023] Specifically, the porous lattice structure includes a plurality of porous lattice structure layers connected layer by layer, the unit cell of the porous lattice structure layer is a five-mode superstructure composed of double cone rods, and the unit cell is preferably in the shape of a regular octahedron, wherein the middle diameter of the double cone rods is larger than the diameters at both ends.

[0024] Preferably, the matrix structure of the five-mode superstructure is preferably a diamond lattice structure. Figure 3 A schematic diagram of a five-mode superstructure consisting of double-tapered rods is shown.

[0025] Preferably, in the five-mode superstructure, the diameters of the two ends of the double-cone rod are 0.17 mm-0.23 mm, and the middle diameter is 0.25 mm-0.4 mm.

[0026] As a preferred embodiment, the length L of the double cone rod of the five-mode superstructure is mm.

[0027] Preferably, the side length of a unit cell of the porous lattice structure is 2 mm, and the size of the unit cell is 2 mm×2 mm×2 mm.

[0028] Preferably, the overall average volume fraction of the porous lattice structure is 9%-11%, which matches the cancellous bone in the human body; further preferably, the average volume fraction of the porous lattice structure is 9.19%.

[0029] Preferably, the diameters of both ends of the double cone rods between different layers of the porous lattice structure remain unchanged, while the middle diameters of the double cone rods of different layers are different and adjustable. This design can ensure tight connection between layers and adjust the porosity and relative density of the porous lattice structure layer.

[0030] Preferably, the dual gradient distribution of the porous lattice structure is that the middle diameter of the double cone rods in the upper and lower layers is the largest and the porosity is the smallest; the middle diameter of the double cone rods in the middle layer is the smallest and the porosity is the largest, and the porosity gradually increases from the top to the middle.

[0031] For ease of understanding, Figure 4 The main view of a porous double-gradient five-mode lattice bone scaffold is shown, where d represents the diameters of both ends of the double-cone rod, d is directly selected as 0.2 mm, and D represents the middle diameter of the double-cone rod, and D is selected in the range of 0.25 mm-0.40 mm.

[0032] Preferably, in the single-layer structure, the relative density of the porous lattice structure layer is 7% to 15%.

[0033] It should be noted that relative density is the ratio of the actual density of a material to its theoretical density (i.e. the density in a fully dense state).

[0034] It is clear that in other embodiments, the porosity and relative density of each layer of the porous lattice structure can be adjusted by adjusting the middle diameters of different layers of double-cone rods according to the actual required density, thereby achieving adjustment of the porous lattice structure.

[0035] Furthermore, the materials used in the porous dual-gradient bone scaffold include but are not limited to NiTi shape memory alloy powder with a nearly equiatomic ratio, wherein the mass fraction of Ni element is 55.75% and the powder particle size is 15μm-53μm. Such powder has good shape memory performance and the particle size is suitable for printing by laser powder bed fusion technology. For ease of understanding, Figure 5 The performance diagram of NiTi shape memory alloy, the raw material of the bone scaffold, is shown.

[0036] Furthermore, the shape memory effect described in this solution refers to the ability to recover to its original shape after compression at low temperature. Figure 6 shown.

[0037] Furthermore, the porous dual-gradient bone scaffold is manufactured by an additive manufacturing method, preferably by laser powder bed melting technology. The shape memory deformation temperature of the scaffold can be regulated by adjusting the parameters of the laser powder bed melting technology. As a preferred embodiment, the austenite transformation termination temperature is generally around body temperature (37°C).

[0038] Under this design, the mechanical properties of the bone scaffold are regulated through additive manufacturing to ensure matching. The bone scaffold can be compressed and directly implanted into the defective part of the human bone. After adapting to the body temperature, it will recover its shape and promote the repair and growth of the defective part of the human bone.

[0039] The present application also discloses a preparation method for preparing any of the above-mentioned porous dual-gradient bone scaffolds with shape memory effect, the preparation method comprising the following steps: S1: Based on the known characteristics of bone structure, a porous lattice structure model with interconnected internal pores and a porosity showing a double gradient change is constructed.

[0040] The specific steps of constructing the porous lattice structure model include: S11: construct a five-mode superstructure model composed of double cone rods (i.e., construct a five-mode superstructure unit cell); S12: Based on the five-mode superstructure model, construct a preliminary periodically arranged porous lattice structure layer model (i.e., construct a single-layer structure); S13: Based on the known bone structure characteristics, the diameter of the double cone rods in the porous lattice structure layer model is set according to the porosity requirement to obtain multiple porous lattice structure layer models with different porosities; S14: Combine porous lattice structure layer models with different porosities to ensure complete integration between layers and present a double gradient distribution that matches bones (such as human bones), so as to form a porous lattice structure model with a double gradient change in porosity (i.e., construct an overall model).

[0041] For ease of understanding, in some specific embodiments, the specific steps of constructing and combining porous lattice structure layers with different porosities are as follows: A double-cone rod is selected with the diameters of both ends kept constant, and the middle diameter is changed according to the distribution of porosity, and a 7×7 array is constructed in the horizontal XY direction (in other embodiments, arrays with other row and column combinations may also be used) to construct a single-layer porous lattice structure layer; The porosity of a single layer is changed by changing the size of the middle diameter of the double cone rod, and layers of different porosities are derived according to the required distribution of the double gradient; The layers are combined according to the porosity distribution to ensure that the end points of the upper surface of the lower layer and the lower surface of the upper layer completely overlap, so that the pores between the layers are connected. The porosity distribution is that the middle diameter of the upper and lower double cone rods is large and the porosity is low, and the middle layer double cone rod has a small middle diameter and a high porosity.

[0042] S2: Slice the porous lattice structure model to obtain three-dimensional slice data; S3: Using memory material as raw material, porous dual-gradient bone scaffolds with shape memory effect were prepared by layer-by-layer printing based on three-dimensional slice data.

[0043] Among them, it is preferred to use near-equiatomic ratio NiTi alloy powder with shape memory effect as raw material, and use laser powder bed melting technology to print layer by layer to manufacture a porous dual-gradient bone scaffold with shape memory effect.

[0044] The laser power of the laser powder bed fusion technology used is preferably 200-300W, and the scanning rate is preferably 900-1300mm / s. In some specific embodiments, the printing parameters of the laser powder bed fusion technology used are: laser power 250W, scanning speed 1100mm / s, and layer thickness 40μm.

[0045] For ease of understanding, Figure 7 A fabrication flow chart of a porous dual-gradient bone scaffold is shown.

[0046] Example: The COMSOL software is used to construct a five-mode superstructure unit cell. First, a trapezoid with variable parameter middle diameter and end diameter is constructed on the sketch. A double cone rod is constructed by rotation and mirroring. The double cone rod constructs the unit cell in space according to the five-mode superstructure configuration. After the unit cell is constructed, a 7×7 array is constructed in the horizontal direction. The array size can be changed according to specific usage. A single-layer five-mode superstructure lattice is constructed and exported as an igs model file.

[0047] Combined with the requirements of bone structure unit cells, according to the requirements of porosity, the size of the middle diameter is changed, and the above steps are repeated to derive the single-layer structure of other layers. After all single-layer models are built, all igs model files are imported into the COMSOL model, and the structure is arranged according to the arrangement of the dual-gradient porosity to ensure that the end diameters coincide with each other. The above single-layer model is processed by Boolean operation to obtain the intersection and construct the overall dual-gradient structure. The obtained model is repaired and sliced ​​in Magics software.

[0048] The fused deposition modeling technology is used for manufacturing, using NiTi alloy powder with a near-equiatomic ratio. The additive manufacturing equipment melts and deposits the powder layer by layer according to the three-dimensional slice data to obtain a porous dual-gradient bone scaffold with shape memory effect.

[0049] In general, under the design of this scheme, the porous double-gradient bone scaffold can imitate the porosity and arrangement of human cortical bone and cancellous bone. By adjusting the middle diameter and the diameters at both ends of the single-cell double-cone rod structure, the porosity of the porous lattice structure can be controlled. Then, the gradient pore distribution structure is set according to the internal structure of human bones, and the double-gradient pore structure is constructed by overlapping the layers, and the internal pores are connected. The porous bone scaffold can adapt to the human body environment and ensure the transmission of human bone nutrients and the repair of defective parts, promote the growth and repair of defective parts, and is particularly suitable for the treatment of lesions in cancellous bones inside the human body.

[0050] In addition, this porous dual-gradient bone scaffold uses NiTi alloy powder with shape memory effect and is manufactured by laser powder bed melting technology. It has high manufacturing precision and can customize the porous complex precision structure of the defect site. The printed scaffold has a shape memory effect and can be compressed in a low-temperature environment in vitro, effectively reducing the size of the scaffold. During the operation, only a smaller wound can be opened at the defect site. After being implanted in the human body during surgery, the temperature rises to the human body temperature, and a phase transition occurs inside the scaffold, so the shape is restored, and the size increases to the shape of the defect site predetermined before compression, and it completely matches the defect site. Therefore, under this design, the surgical wound can be effectively reduced by utilizing the shape memory effect, and after implantation, it matches the irregular defect site, and stress stimulates bone tissue repair.

[0051] It should be understood that expressions such as "include" and "may include" used in this application indicate the existence of the disclosed functions, operations or constituent elements, and do not limit one or more additional functions, operations and constituent elements. In this application, terms such as "include" and / or "have" may be interpreted as indicating specific characteristics, numbers, operations, constituent elements, components or combinations thereof, but may not be interpreted as excluding the existence or possibility of adding one or more other characteristics, numbers, operations, constituent elements, components or combinations thereof.

[0052] It should be understood that the terms "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0053] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0054] In this application, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0055] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application shall be included in the scope of protection of the present application.

Claims

1. A porous dual-gradient bone scaffold with shape memory effect, characterized in that: The invention comprises a porous lattice structure with multiple structural layers made of memory material, the internal pores of the porous lattice structure are connected, and the porosity of the porous lattice structure presents a double gradient change.

2. The porous dual-gradient bone scaffold according to claim 1, characterized in that: The unit cell of the porous lattice structure is a five-mode superstructure composed of double cone rods, wherein the middle diameter of the double cone rods is larger than the diameters at both ends.

3. The porous dual-gradient bone scaffold according to claim 2, characterized in that: The matrix structure of the five-mode superstructure is a diamond lattice structure.

4. The porous dual-gradient bone scaffold according to claim 2, characterized in that: The diameters of the two ends of the double cone rod are 0.17mm-0.23mm, and the middle diameter is 0.25mm-0.4mm.

5. The porous dual-gradient bone scaffold according to claim 2, characterized in that: In the porous lattice structure, the double cone rods in different layers have the same diameter at both ends and different diameters in the middle.

6. The porous dual-gradient bone scaffold according to any one of claims 1 to 5, characterized in that: The porosity of the porous lattice structure gradually increases from both ends to the middle.

7. The porous dual-gradient bone scaffold according to any one of claims 1 to 5, characterized in that: The memory material is NiTi shape memory alloy powder.

8. The porous dual-gradient bone scaffold according to claim 7, characterized in that: The mass fraction of Ni element in the NiTi shape memory alloy powder is 55.75%, and the powder particle size is 15 μm-53 μm.

9. A preparation method for preparing a porous dual-gradient bone scaffold with shape memory effect as claimed in any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: Based on the known characteristics of bone structure, a porous lattice structure model with interconnected internal pores and a porosity showing a double gradient change was constructed. Slice the porous lattice structure model to obtain three-dimensional slice data; Using memory material as raw material, porous dual-gradient bone scaffolds with shape memory effect are prepared by printing layer by layer based on three-dimensional slice data.

10. The preparation method according to claim 9, characterized in that: The steps of constructing the porous lattice structure model include: Construct a five-mode superstructure model consisting of double-conical rods; Based on the five-mode superstructure model, a porous lattice structure layer model is constructed; Based on the known bone structure characteristics, the diameters of the double cone rods in the porous lattice structure layer model are set to obtain multiple porous lattice structure layer models with different porosities; The porous lattice structure layer models with different porosities are combined to form a porous lattice structure model with a porosity showing a double gradient change.

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