CN-122005921-A - Multi-layer degradable porous bone scaffold for bone repair and preparation method thereof

CN122005921ACN 122005921 ACN122005921 ACN 122005921ACN-122005921-A

Abstract

The invention provides a multi-layer degradable porous bone scaffold for bone repair and a preparation method thereof, which are novel porous bone scaffold structures based on three-period minimum curved surfaces, and the porous bone scaffold comprises an outer layer, a middle transition layer and an inner layer, wherein each layer is of a porous structure, the porosity is sequentially reduced from the inner layer to the outer layer so as to simulate the gradient pore structure and the gradient mechanical property of human bones, the thickness of the outer layer is set according to the thickness of bone compact at a used part, the thickness of the inner layer is set according to the thickness of bone compact at the used part, and the middle transition layer is used for smooth connection of the pore structures and the mechanical properties of the inner layer and the outer layer. The invention can simulate the gradient pore structure of human bones through the design of the multi-layer gradient structure, realize the high fitting with the real bone structure of the human body, improve the bone ingrowth efficiency, promote the bone repair effect, and simultaneously have good mechanical support performance and controllable degradation performance.

Inventors

LI JINGYI
ZHANG JUNSONG
MENG JUAN
ZHANG SHENJUN
FU YUE
BAI XIANGNAN
LIU YAOXIN
WANG JING

Assignees

大连医科大学

Dates

Publication Date: 20260512
Application Date: 20251230

Claims (10)

1. A multi-layer degradable porous bone scaffold for bone repair is characterized by comprising an outer layer, a middle transition layer and an inner layer, wherein each layer is of a porous structure, the porosity is sequentially reduced from the inner layer to the outer layer so as to simulate the gradient pore structure and the gradient mechanical property of human bones, the thickness of the outer layer is set according to the thickness of bone compact at a used part, the thickness of the inner layer is set according to the thickness of bone compact at the used part, the middle transition layer is used for smooth connection of the pore structure and the mechanical property of the inner layer, the outer shape of the bone scaffold is determined according to the actual defect shape of a damaged part of a bone, each layer is constructed based on a TPMS curved surface, and each layer of unit cell structure is determined according to the required porosity.
2. The multi-layered degradable porous bone scaffold for bone repair of claim 1, wherein the bone scaffold is generally cylindrical and the inner layer is generally cylindrical, and the outer column is sequentially wrapped with an intermediate transition layer and an outer layer for bone repair of long bones, wherein the outer radius ratio of the outer layer to the intermediate transition layer to the inner layer is 13:9.15:6.44-16.6:11.7:8.24.
3. The multi-layer degradable porous bone scaffold for bone repair according to claim 1, wherein the bone scaffold is of a flat structure, the inner layer is of a sheet shape, and the two sides of the inner layer are sequentially provided with a middle transition layer and an outer layer for flat bone repair, wherein the thickness ratio of the outer layer to the middle transition layer to the inner layer is (7-11): 1:2.
4. A multi-layered degradable porous bone scaffold for bone repair according to any one of claims 1-3, wherein the porosity of the bone scaffold is constant after continuously increasing from the outer periphery of the outer layer to the outer periphery of the inner layer, wherein the inner layer has a porosity of 30% -80% and the outer layer has a minimum porosity of 20% -40%.
5. The multi-layer degradable porous bone scaffold for bone repair according to claim 4, wherein the outer layer of the bone scaffold adopts a D-type, F-RD-type or I-WP-type TPMS structure, the middle transition layer adopts an F-RD-type, G-type or F-KS-type TPMS structure, the inner layer adopts a P-type, F-KS-type or N-type TPMS structure, the unit cell structures of all layers adopt a cube structure, and the unit cell size is (0.1-2) x (0.1-2) mm.
6. The multi-layered degradable porous bone scaffold for bone repair of claim 1, wherein the bone scaffold is made of biodegradable medical materials including one or more of polylactic acid, polycaprolactone-tricalcium phosphate, hydroxyapatite, medical metals and alloys thereof.
7. A multi-layered degradable porous bone scaffold for bone repair according to any one of claims 1, characterized in that the scaffold is made of degradable zinc-iron alloy and the mass ratio of zinc to iron is 5:5-8:2.
8. A method of preparing a degradable porous bone scaffold for bone repair according to any one of claims 1-6, comprising: S1, detecting appearance and bone property parameters of a damaged part, and determining bone scaffold parameters, wherein the bone property parameters comprise bone density, thickness of each layer, porosity gradient, strength gradient and permeability, and the bone scaffold parameters comprise material types, content proportion, thickness of each layer of a bone scaffold, porosity change gradient of each layer of the bone scaffold, unit cell type and unit cell size of each layer of the bone scaffold; s2, designing a three-dimensional model of the bone scaffold by using Python; S3, preparing the required bone scaffold by adopting a 3D printing method based on the three-dimensional model designed by the S2.
9. The method for preparing a multi-layered degradable porous bone scaffold for bone repair according to claim 8, wherein in S1, the method for determining the bone scaffold parameters comprises the steps of constructing a bone scaffold parameter model by using a machine learning technology, specifically: S1.1, constructing a data set, namely collecting sample data, extracting key characteristics, wherein the key characteristics comprise bone type, bone density, bone compact thickness, porosity gradient, strength gradient, permeability, material type, content proportion of each component of the material, thickness of each layer of a bone support, porosity change gradient of each layer of the bone support, unit cell type and unit cell size of each layer of the bone support; S1.2, based on a random forest algorithm, adopting a fusion strategy of a classification and regression dual-task framework, and respectively utilizing a multi-output classifier and a multi-output regression to package classification and regression sub-models to construct and obtain a bone scaffold parameter model; setting input characteristics and output characteristics, wherein the input characteristics comprise pretreated bone type, bone density, bone compact thickness, bone spongy thickness, porosity gradient, strength gradient and permeability; the set output characteristics comprise material types, content proportion of each component of the material, thickness of each layer of the bone scaffold, porosity gradient of each layer of the bone scaffold, unit cell type and unit cell size of each layer of the bone scaffold; s1.3, setting a constraint range for the bone scaffold parameter model, and training the bone scaffold parameter model by using the sample set data in the S1.1; s1.4, inputting the detected bone property parameters of the damaged part into a bone scaffold parameter model to obtain bone scaffold parameters.
10. The method for preparing a multi-layered degradable porous bone scaffold for bone repair according to claim 8, wherein the S2 specifically comprises: S2.1, establishing a coordinate system by using Python and taking a center point of the lower surface of the model as an origin of a coordinate axis, establishing a basic model according to the overall dimension of the damaged part obtained in the S1 and the bone type of the damaged part, taking the origin of the coordinate axis as a vertical axis towards interfaces of all layers, defining a layer closest to the origin as a first layer, and then, taking a second layer and so on; S2.2, constructing a modeling equation set: 1) Constructing a single cell structural equation of each layer through a TPMS general formula: (1) Wherein, the As the structural equation of the i-th layer, Is the kth element vector in a certain layer space, K is the total number of element vectors in the corresponding layer space, Is the magnitude factor of the kth element vector, Is a position vector of the european space, Is the phase offset of the kth element vector, Is a function of the unit cell size, wherein, The four value methods are as follows: (2) (3) (4) (5) In the formula, In order to control the offset function of the porosity, the formula (2) represents a volume-free curved surface, the formula (3) represents a value to the outer side of the curved surface on the basis of the volume-free curved surface, the formula (4) represents a value to the inner side of the curved surface on the basis of the volume-free curved surface, and the formula (5) represents a value to the inner side of the curved surface on the basis of the volume-free curved surface of-0.8 to -Taking a value in the range of 0.8 towards the inner side and the outer side of the curved surface; 2) Constructing a multi-layer hybrid model, comprising: The multi-layer function is adopted: (6) Wherein, the Is a multi-layer function, n is the total layer number of the bone scaffold, Is the ith layer and Sigmoid activation function of layer boundary surface and its setting , , wherein, The formula is as follows: (7) (8) In the formula, As a function of the boundary(s), Is the coefficient of variation of the coefficient of variation, Is the sum of the thicknesses of the 1 st layer and the i th layer, and ; 3) Constructing a gradient change function of each layer structure: (9) (10) (11) In the formula, 、 As a coefficient of the amount of offset, 、 Is a periodic coefficient; Substituting the formula (11) into the formula (10), and expanding the formula (1) by combining the bone scaffold parameters determined in the step S1 to obtain structural equations of all layers, substituting the formula (11) into the formula (9), adding the structural equations of the corresponding layers to obtain model equations of all layers, substituting the formula (8) into the formula (7), and substituting the model equations of all layers into the formula (6) simultaneously to obtain a final model total equation; S2.3, based on a final model total equation, utilizing Python to manufacture a three-dimensional model of the required bone scaffold.

Description

Multi-layer degradable porous bone scaffold for bone repair and preparation method thereof Technical Field The invention belongs to the technical field of biomedical materials and bone tissue engineering, and particularly relates to a multi-layer degradable porous bone scaffold for bone repair and a preparation method thereof. Background There are many fracture prone sites in the human body such as the femoral neck, femoral shaft, radius, skull, ribs, etc. In order to ensure the mechanical strength of fracture parts, currently, bone repair materials such as titanium alloy, stainless steel and the like are commonly used, but the materials are often not degradable, and if complications such as pain, infection or abnormal positions and the like occur, the materials are often required to be taken out through secondary operation, so that the pain and the risk of patients are increased. In recent years, degradable materials such as zinc-based alloys and iron-based alloys have received attention because of their good biocompatibility and controllable degradation properties. However, the existing degradable bone scaffold is single in structure, uniform in porosity distribution, and quite different from the gradient structure of human bones, so that the problems of poor mechanical properties and matching effect with bone tissues, insufficient bone ingrowth or the like are easy to occur, and ideal osseointegration effect is difficult to realize. Disclosure of Invention The invention provides a multi-layer degradable porous bone scaffold for bone repair and a preparation method thereof, which are novel porous bone scaffold structures based on three-period minimum curved surfaces (TPMS), and can simulate the gradient pore structure of human bones through multi-layer gradient structure design, realize high fitting with the real bone structure of the human body, improve bone ingrowth efficiency, promote bone repair effect, and simultaneously have good mechanical supporting performance and controllable degradation performance. In order to achieve the above object, the present application provides the following solutions: The multi-layer degradable porous bone scaffold for bone repair comprises an outer layer, an intermediate transition layer and an inner layer, wherein each layer is of a porous structure, the porosity is sequentially reduced from the inner layer to the outer layer so as to simulate the gradient pore structure and the gradient mechanical property of human bones, the thickness of the outer layer is set according to the thickness of bone compact of a used part and is used for realizing mechanical support, the thickness of the inner layer is set according to the thickness of bone compact of the used part and is used for providing sufficient space for migration, adhesion and proliferation of cells, meanwhile, permeation of nutrients and discharge of metabolic wastes are facilitated, infiltration and fixation of bone cells and growth of new bone tissues are promoted, the intermediate transition layer is arranged between the outer layer and the inner layer and is used for smooth connection of the pore structure and the mechanical property of the inner layer, the appearance of the bone scaffold is determined according to the actual defect shape of a broken bone part, each layer is constructed based on a TPMS curved surface and ensures connectivity and mechanical anisotropy, and each layer of cell structure is determined according to the required porosity. In some embodiments, the bone scaffold is entirely column-like, the inner layer is column-like, and the outer column body thereof sequentially wraps the intermediate transition layer and the outer layer for long bone repair. As a preferred mode, the outer circle radius ratio of the outer layer, the middle transition layer and the inner layer of the bone scaffold is 13:9.15:6.44-16.6:11.7:8.24. In some embodiments, the bone scaffold is in a flat structure, the inner layer is in a sheet shape, and the two sides of the bone scaffold are sequentially provided with a middle transition layer and an outer layer for repairing the flat bone. As a preferable mode, the thickness ratio of the outer layer, the intermediate transition layer and the inner layer is (7-11): 1:2. In some embodiments, the porosity of the bone scaffold is constant after continuously increasing from the outer periphery of the outer layer to the outer periphery of the inner layer, wherein the inner layer has a porosity of 30% -80% and the outer layer has a minimum porosity of 20% -40%. In some embodiments, the outer layer of the bone scaffold adopts a D-type, F-RD-type or I-WP-type TPMS structure, the middle transition layer adopts a F-RD-type, G-type or F-KS-type TPMS structure, the inner layer adopts a P-type, F-KS-type or N-type TPMS structure, the unit cell structures of all the layers adopt a cube structure, and the unit cell size is (0.1-2) x (0.1-2) mm. As a preferable mode, the outer layer of