阅读说明：本技术 一种骨组织工程梯度多孔镁基金属构件体及其制备方法 (Bone tissue engineering gradient porous magnesium-based metal component body and preparation method thereof ) 是由 刘辰 柏关顺 徐永东 朱秀荣 任政 庞松 王军 邵志文 于 2019-09-11 设计创作，主要内容包括：本发明涉及一种骨组织工程梯度多孔镁基金属构件体,其特征在于：至少包括内核预制体、位于内核预制体外围且呈环状的外层预制体及位于内核预制体和外层预制体之间且呈环状的中间层预制体,所述内核预制体、中间层预制体及外层预制体均具有孔隙,且三者的孔隙均相连通,并且所述内核预制体、中间层预制体及外层预制体的孔隙率依次减小。本发明还涉及一种制备方法。在植入人体后能满足不同时期对降解速率和力学性能之间动态匹配的不同需求。(The invention relates to a gradient porous magnesium-based metal component body for bone tissue engineering, which is characterized in that: the composite material at least comprises an inner core preform, an outer layer preform which is positioned at the periphery of the inner core preform and is annular, and an intermediate layer preform which is positioned between the inner core preform and the outer layer preform and is annular, wherein the inner core preform, the intermediate layer preform and the outer layer preform are provided with pores, the pores of the inner core preform, the pores of the intermediate layer preform and the pores of the outer layer preform are communicated, and the porosity of the inner core preform, the porosity of the intermediate layer preform and the porosity of the outer layer preform are reduced in sequence. The invention also relates to a preparation method. After being implanted into a human body, the material can meet different requirements of dynamic matching between degradation rate and mechanical property in different periods.)

1. A bone tissue engineering gradient porous magnesium-based metal component body is characterized in that: the composite material at least comprises an inner core preform, an outer layer preform which is positioned at the periphery of the inner core preform and is annular, and an intermediate layer preform which is positioned between the inner core preform and the outer layer preform and is annular, wherein the inner core preform, the intermediate layer preform and the outer layer preform are provided with pores, the pores of the inner core preform, the pores of the intermediate layer preform and the pores of the outer layer preform are communicated, and the porosity of the inner core preform, the porosity of the intermediate layer preform and the porosity of the outer layer preform are reduced in sequence.

2. The bone tissue engineering gradient porous magnesium-based metal component body of claim 1, wherein: the core preform is formed by pressing magnesium powder subjected to ball milling, and the granularity of the ball-milled magnesium powder of the core preform is 500-1000 microns.

3. The bone tissue engineering gradient porous magnesium-based metal component body of claim 2, wherein: the magnesium powder of the intermediate layer preform is a preform formed by pressing mixed powder formed by mixing ball-milled magnesium powder and gas-atomized magnesium powder, and the granularity of the ball-milled magnesium powder of the intermediate layer preform is 200-500 microns and the granularity of the gas-atomized magnesium powder is 50-200 microns.

4. The bone tissue engineering gradient porous magnesium-based metal component body of claim 3, wherein: the magnesium powder of the outer-layer prefabricated body is also a prefabricated body formed by pressing mixed powder of ball-milled magnesium powder and gas-atomized magnesium powder, the granularity of the ball-milled magnesium powder of the outer-layer prefabricated body is 100-200 mu m, and the granularity of the gas-atomized magnesium powder is 1-50 mu m.

5. A method for preparing the gradient porous magnesium-based metal component body for bone tissue engineering of claim 4, which is characterized in that: the method sequentially comprises the following steps:

(1) preparing a preform by using a cold isostatic press under constant external pressure:

pressing ball-milled magnesium powder with the granularity of 500-1000 mu m to obtain an inner core preform with higher porosity; then adding ball-milled magnesium powder with the granularity of 200-500 mu m and gas-atomized magnesium powder with the granularity of 50-200 mu m around the inner core preform, uniformly mixing, and then performing second pressing under constant external pressure to obtain an intermediate layer preform with the porosity smaller than that of the inner layer preform at the periphery of the intermediate layer preform; finally, adding ball-milled magnesium powder with the granularity of 100-200 mu m and gas-atomized magnesium powder with the granularity of 1-50 mu m around the intermediate preform, uniformly mixing, and then pressing for the third time under constant external pressure, so that an outer layer preform with the porosity smaller than that of the intermediate layer preform is prepared at the periphery of the intermediate layer preform, and at the moment, the final preform with the inner layer preform, the intermediate layer preform and the outer layer preform is prepared;

(2) and (3) carrying out vacuum sintering on the final prefabricated body to obtain the bone tissue engineering gradient porous magnesium-based metal member with the pores in gradient distribution.

6. The method of claim 5, wherein: the inner core preform, the middle layer preform and the outer layer preform are all preforms which are formed by pressing under the same constant external pressure, and the constant external pressure is 40-60 MPa.

7. The method of claim 5, wherein: before the step (1), preparing gas atomized magnesium powder and ball milled magnesium powder by taking high-purity magnesium or magnesium alloy powder as a base material:

preparing gas atomized magnesium powder by adopting a gas atomization powder preparation method: cleaning the surface of a substrate material, melting the substrate material into magnesium liquid in gas atomization powder preparation equipment, centrifugally throwing the constant-temperature and constant-speed magnesium liquid into fog drops through centrifugal atomization in a high-speed rotating manner, cooling the fog drops by circulating inert gas to form powder, and then respectively obtaining gas atomization magnesium powder with the granularity of 1-50 mu m and gas atomization magnesium powder with the granularity of 50-200 mu m through step-by-step separation;

preparing ball-milled magnesium powder by adopting a ball-milling powder preparation method: cleaning the surface of a base material, putting the base material into a ball mill, introducing argon gas to perform intermittent ball milling, naturally cooling after the ball milling is finished, and obtaining magnesium powder with the granularity of 500-1000 microns, 200-500 microns and 100-200 microns by using a screen.

8. The method of claim 6, wherein: the intermittent ball milling in the preparation process of the ball-milled magnesium powder is stopped for half an hour after half an hour of each ball milling, and the time of the intermittent ball milling is 12 to 15 hours in total.

9. The method of claim 6, wherein: in the preparation of gas atomized magnesium powder, powder formed by cooling circulating inert gas is spherical powder; and the magnesium powder prepared in the preparation of the ball-milled magnesium powder is irregular magnesium powder.

10. The method of claim 6, wherein: the alloy magnesium powder in the base material of the alloy magnesium powder is a binary magnesium alloy system, or a ternary magnesium alloy system, or a multi-element magnesium alloy system.

Technical Field

The invention relates to the technical field of medical instruments implanted in orthopedics, in particular to a bone tissue engineering gradient porous magnesium-based metal component body and a preparation method thereof.

Background

Bone defects are one of the common clinical conditions in orthopedic medicine, and bone defects of a certain size can heal by themselves, while bone defects of a larger size are generally difficult to heal automatically and need to be treated by bone grafting or replacement implantation.

The existing bone defect treatment method is a bracket material made of magnesium-based metal material, the bracket material is used as a basic component of tissue engineering bone, and the magnesium-based metal material has the characteristics of good biocompatibility, degradability and absorbability in human body and the like, and is a novel biodegradable (absorbable) metal material with great clinical application prospect. Because the magnesium-based metal has the characteristics of a metal material, the strength, the plasticity and the like of the magnesium-based metal are far superior to those of ceramic and polymer absorbable materials which are clinically applied at present, and meanwhile, the elastic modulus and the density of the magnesium-based metal are closer to those of human bone tissues, and the magnesium-based metal has the advantages of capability of promoting the generation of surrounding new bones and the like, so that the magnesium-based metal has great potential and market competitiveness when being applied as an absorbable bone implant device. The magnesium-based metal material is prepared into a porous structure, has the characteristics of low elastic modulus, proper strength, excellent biocompatibility and the like, can provide a three-dimensional growth space for cells, has biological activity, and can induce differentiation and proliferation of osteoblasts and ingrowth of blood vessels so as to fulfill the aims of repairing bone injury and bone reconstruction functions, so that the magnesium-based metal material is considered as an ideal bone tissue engineering material.

Bone defect repair can generally be divided into three stages: the first week or so is an inflammatory phase, then a repair phase, which is about 3-6 months depending on the repair site, and finally a reconstruction phase. The ideal porous magnesium metal scaffold material for bone tissue engineering should have a low degradation rate in the first two stages to maintain sufficient mechanical strength to realize the function of fixing and supporting. In the bone reconstruction stage, the mechanical property of the material is gradually reduced, the load is transferred to the bone tissue, the degradation rate is kept fast, and finally the material is completely degraded when the bone tissue is healed. Therefore, certain requirements are required for the matching relationship between the degradation rate and the mechanical property of the magnesium alloy material for the bone tissue engineering scaffold. Most of the porous magnesium scaffolds prepared by different methods at present are single-structure materials, and cannot meet different requirements of dynamic matching between degradation rate and mechanical property at different periods after the materials are implanted, so that development of a preparation method of a gradient porous magnesium metal scaffold material is of great importance.

The preparation method of the porous magnesium mainly comprises a precision casting method, a solid/gas eutectic solidification method, a seepage casting method, a laser drilling method, a powder metallurgy method and the like. The method has the problems that the prepared porous magnesium has a single structure, the gradient porous magnesium metal bracket structure is difficult to prepare, the use requirements on the performance of the porous magnesium bracket material in different periods of implantation cannot be met, and the bone repair effect is seriously influenced. The powder metallurgy method is to mix metal powder alone or metal powder and pore-forming agent (additive for generating pore structure in the material) uniformly according to a certain proportion, then to press and form under a certain pressure to obtain a green body, and then to prepare the porous metal material by sintering and removing the pore-forming agent. The method has the characteristics of good mechanical property, convenient adjustment of porosity and pore size and the like, and has potential application value in the aspect of preparing gradient porous metal materials. At present, the gradient porous magnesium metal material is prepared by a powder metallurgy method mainly by adjusting the applied pressure, the mixing ratio between metal powder and pore-forming agent and the like in the powder metallurgy process. The load and the loading mode of the external pressure need to be accurately controlled, so that the dependence on pressure equipment is high; when the gradient porous magnesium is prepared by adjusting the mixing ratio between the metal powder and the pore-forming agent, the pore-forming agent residue in the sintered product is easily caused, and the adverse effect on the growth of cells around the implant is generated.

Disclosure of Invention

The first technical problem to be solved by the invention is to provide a bone tissue engineering gradient porous magnesium-based metal component body which meets different requirements on dynamic matching between degradation rate and mechanical property in different periods aiming at the current situation of the prior art.

The second technical problem to be solved by the invention is to provide a preparation method of a bone tissue engineering gradient porous magnesium-based metal member without introducing a pore-forming agent aiming at the current situation of the prior art.

The technical scheme adopted by the invention for solving the first technical problem is as follows: a bone tissue engineering gradient porous magnesium-based metal component body is characterized in that: the composite material at least comprises an inner core preform, an outer layer preform which is positioned at the periphery of the inner core preform and is annular, and an intermediate layer preform which is positioned between the inner core preform and the outer layer preform and is annular, wherein the inner core preform, the intermediate layer preform and the outer layer preform are provided with pores, the pores of the inner core preform, the pores of the intermediate layer preform and the pores of the outer layer preform are communicated, and the porosity of the inner core preform, the porosity of the intermediate layer preform and the porosity of the outer layer preform are reduced in sequence.

In order to obtain larger porosity of the core preform, the core preform is formed by pressing magnesium powder subjected to ball milling, and the granularity of the ball-milled magnesium powder of the core preform is between 500 and 1000 microns. When the granularity of the ball-milled magnesium powder is less than 500 mu m, the porosity of the inner core preform is relatively small, when the granularity of the ball-milled magnesium powder is more than 1000 mu m, microscopic pores are difficult to obtain, and when the granularity of the ball-milled magnesium powder is between 500 mu m and 1000 mu m, the required large porosity can be easily obtained.

In order to obtain a preform with a porosity smaller than that of the core preform, preferably, the magnesium powder of the intermediate layer preform is a preform formed by pressing mixed powder obtained by mixing ball-milled magnesium powder and gas-atomized magnesium powder, and the particle size of the ball-milled magnesium powder of the intermediate layer preform is 200 μm to 500 μm and the particle size of the gas-atomized magnesium powder is 50 μm to 200 μm. In this manner, the porosity of the inner core preform is graded with the porosity of the intermediate layer preform.

In order to obtain a preform with porosity smaller than that of the intermediate layer preform, the magnesium powder of the outer layer preform is also a preform formed by pressing mixed powder of ball-milled magnesium powder and gas-atomized magnesium powder, and the granularity of the ball-milled magnesium powder of the outer layer preform is 100-200 μm and the granularity of the gas-atomized magnesium powder is 1-50 μm. In this way, the porosity of the inner core preform, the porosity of the intermediate layer preform, and the porosity of the outer layer preform form a gradient.

The technical scheme adopted by the invention for solving the second technical problem is as follows: a preparation method of a bone tissue engineering gradient porous magnesium-based metal component body is characterized by comprising the following steps: the method sequentially comprises the following steps:

(1) preparing a preform by using a cold isostatic press under constant external pressure:

pressing ball-milled magnesium powder with the granularity of 500-1000 mu m to obtain an inner core preform with higher porosity; then adding ball-milled magnesium powder with the granularity of 200-500 mu m and gas-atomized magnesium powder with the granularity of 50-200 mu m around the inner core preform, uniformly mixing, and then performing second pressing under constant external pressure to obtain an intermediate layer preform with the porosity smaller than that of the inner layer preform at the periphery of the intermediate layer preform; finally, adding ball-milled magnesium powder with the granularity of 100-200 mu m and gas-atomized magnesium powder with the granularity of 1-50 mu m around the intermediate preform, uniformly mixing, and then pressing for the third time under constant external pressure, so that an outer layer preform with the porosity smaller than that of the intermediate layer preform is prepared at the periphery of the intermediate layer preform, and at the moment, the final preform with the inner layer preform, the intermediate layer preform and the outer layer preform is prepared;

(2) and (3) carrying out vacuum sintering on the final prefabricated body to obtain the bone tissue engineering gradient porous magnesium-based metal member with the pores in gradient distribution.

In order to reduce the operation procedures and facilitate the operation, the inner core preform, the middle layer preform and the outer layer preform are all preforms which are pressed under the same constant external pressure, and the constant external pressure is 40 MPa-60 MPa. When the constant external pressure is less than 40MPa, the prefabricated body is loose, and the overall strength of the prefabricated body is low; when the constant external pressure is more than 60MPa, the degree of compaction of the preform is relatively high, and the porosity of each layer of the preform is easily damaged.

Preferably, before the step (1), the preparation of the gas atomized magnesium powder and the ball milled magnesium powder is carried out by taking high-purity magnesium or magnesium alloy powder as a base material:

preparing gas atomized magnesium powder by adopting a gas atomization powder preparation method: cleaning the surface of a substrate material, melting the substrate material into magnesium liquid in gas atomization powder preparation equipment, centrifugally throwing the constant-temperature and constant-speed magnesium liquid into fog drops through centrifugal atomization in a high-speed rotating manner, cooling the fog drops by circulating inert gas to form powder, and then respectively obtaining gas atomization magnesium powder with the granularity of 1-50 mu m and gas atomization magnesium powder with the granularity of 50-200 mu m through step-by-step separation;

preparing ball-milled magnesium powder by adopting a ball-milling powder preparation method: cleaning the surface of a base material, putting the base material into a ball mill, introducing argon gas to perform intermittent ball milling, naturally cooling the base material after the ball milling is finished, and obtaining magnesium powder with the granularity of 500-1000 microns, 200-500 microns and 100-200 microns by using a screen;

in order to reduce the sintering or sticking of the magnesium powder on the inner wall of the ball milling tank, the intermittent ball milling in the preparation process of the ball milling magnesium powder needs to be stopped for half an hour after half an hour of each ball milling, and the time of the intermittent ball milling is 12 to 15 hours in total. Because the melting point of the magnesium powder is lower, the magnesium powder can be cooled by adopting the intermittent ball milling mode, and the magnesium powder is prevented from being adhered to the inner wall of the ball milling tank.

Preferably, in the preparation of the gas atomized magnesium powder, the powder formed by cooling the circulating inert gas is spherical powder; and the magnesium powder prepared in the preparation of the ball-milled magnesium powder is irregular magnesium powder.

Preferably, the magnesium alloy powder in the magnesium alloy powder as the matrix material is a binary magnesium alloy system, or a ternary magnesium alloy system, or a multi-element magnesium alloy system.

Compared with the prior art, the invention has the advantages that: 1. the porosity of the inner core preform, the porosity of the middle layer preform and the porosity of the outer layer preform of the bone tissue engineering gradient porous magnesium-based metal component material are sequentially reduced, namely the porosity of the inner core preform is greater than the porosity of the middle layer preform, and the porosity of the middle layer preform is greater than the porosity of the outer layer preform; the three porosity factors are different, and different requirements of dynamic matching between the degradation rate and the mechanical property in different periods can be met after the three porosity factors are implanted into a human body, wherein in the two stages (an inflammation reaction stage and a bone repair stage) before bone defect repair, the region with low porosity of the outer layer is slowly degraded, the mechanical property is high, and the sufficient mechanical strength is kept in the two stages before the repair, so that the function of fixed support is realized; in the third stage of bone defect repair (bone reconstruction stage), the degradation of the region with high porosity of the inner layer is accelerated, the mechanical property of the region is gradually reduced, the load is transferred to bone tissues, the rapid degradation rate is kept, and finally, the complete degradation of the component is realized when the bone tissues are healed;

2. the preparation method of the invention is that under the premise of constant external pressure and without introducing different materials such as pore-forming agent, high-purity magnesium or magnesium alloy is used as a substrate material, a prefabricated body is prepared by adjusting the granularity of magnesium powder and the mixing ratio of magnesium powder with different granularities, and then the gradient porous magnesium-based metal member material is prepared under the condition of vacuum sintering process, so that the dependence on pressure equipment can be reduced, and the adverse effect of the residual pore-forming agent on the growth of human cells can be avoided.

Drawings

Fig. 1 is a schematic structural diagram of an embodiment of the present invention.

Detailed Description

The invention is described in further detail below with reference to the accompanying examples.