Degradable stephanoporate magnesium base composite organization engineering stent material by using in the organism
Technical field
What the present invention relates to is a kind of porous magnesium based composites of field of tissue engineering technology, specifically, is degradable stephanoporate magnesium base composite organization engineering stent material by using in a kind of organism.
Background technology
Tissue engineering is to use a small amount of histiocyte behind cultured and amplified in vitro, is adsorbed onto on the good and biomaterial (support) that can be degraded by body of a kind of biocompatibility, is inoculated into then and forms the new tissue with vitality and correlation function in the body.Bone tissue engineer is wherein a kind of, and its biggest advantage is to have formed the biological tissue with vitality.With a large amount of tissue defects of a small amount of tissue repair and can be moulding, for the reparation of tissue defect provides new thinking, new method according to prefabricated shape.Ideal bone, cartilage tissue engineered rack material or cell carrier should have following condition: excellent biological compatibility, and suitable biological degradability, effective surface activity, certain plasticity has three-dimensional porous structure.
The bone tissue engineering stent material of research and development mainly contains degradable high polymer and bioceramic etc. at present, but the mechanical performance of polymer and ceramic material is poor, and the catabolite of polymer for example lactic acid and hydroxyacetic acid etc., if the higher reduction that causes local pH of concentration, damaged tissue.In recent years, research emphasis is transferred on hydroxyapatite and ossein direct compound gradually, but the insufficient strength height of this material, and the implantation that is not suitable for load-bearing bone is replaced and is repaired.Therefore, domestic and international research concentrates in a large number and seeks suitable porous material as new implanting tissue engineering material at present.Can be degraded in vivo, finally be absorbed by body, while material itself is biologically active again, a kind of novel metal based composites that comes to this that the present invention relates to.
Magnesium is one of the abundantest element of reserves on the earth, also is second cation the abundantest in the 4th, cell in the human body, is indispensable important nutrient in the human body.Magnesium promotes the formation of bone and cell in life process, catalysis or activation body 300 plurality of enzymes system.Magnesium plays a crucial role to proteinic synthesizing by the structure of regulating rDNA and RNA in the three big metabolism in vivo.Magnesium has good medical science safety basis as bio-medical material.
Find through literature search prior art, people such as Frank Witte have reported " Biodegradablemagnesium-hydroxyapatite metal matrix composites " (biodegradable magnesium-hydroxyapatite metal-base composites) in 2007 28 volumes of " Biomaterials " (biomaterial) periodical 2163-2174 page or leaf, they strengthen magnesium alloy by cell culture experiments in vitro research hydroapatite particles and are used as bone tissue engineer biodegradable stent feasibility, the cell compatibility that found that the composite material of magnesium alloy that this contains HA enhancing body is good, osteoprogenitor cell on the sample (HBDC), the quantity of osteoblast (MG-63) and macrophage (RAW264.7) is all than matched group (organizational project plastics, TCP) many, and have adjustable machinery and corrosive nature, have good application potential.Also mention other elements such as containing the Al element in the AZ91D magnesium alloy of being studied in the document, though the biocompatibility of magnesium basis is good, but the Al element does not belong to the essential trace element of human body, be considered to have neurotoxicity, be the factor that causes presenile dementia, reduced cytoactive to a certain extent.
Summary of the invention
The present invention is directed to the deficiency of existing conventional stent material, degradable stephanoporate magnesium base composite organization engineering stent material by using in a kind of organism is provided.The present invention adopts the bone tissue engineering stent material of powder metallurgical technique preparation, utilize the chemical reaction of magnesium in aqueous medium to change magnesium ion into, magnesium ion comes adjustment by the metabolism of intravital absorption and kidney, thereby timbering material is degraded and absorbed in vivo gradually.Mg
2+Ion participates in a series of metabolic processes, comprises the formation of osteocyte, accelerated bone healing ability etc., and suitable timbering material as bone tissue engineer promotes the propagation of sticking of osteocyte to multiply, and strengthens self-repairing capability, quickens the speed of repairing from body.The porous magnesium timbering material has excellent biological compatibility and mechanical property basis, can satisfy the requirement of bone tissue engineering stent material comprehensive mechanical property and biological safe preferably.
The present invention is achieved by the following technical solutions, the present invention relates to the degradable material that is used to make porous magnesio composite tissue engineering support in a kind of organism, its component and volume percent content thereof: high-purity magnesium, high-purity Mg-Zn alloy, high-purity Mg-Zn-Ca alloy, high-purity Mg-Zn-Ca-Fe alloy, high-purity Mg-Mn alloy or high-purity Mg-Zn-Mn alloy 70%-20%, HA powder 10%-20%, carbamide 20%-70%, high-purity magnesium and magnesium alloy powder purity are more than or equal to 99.99%.
The purity of described carbamide is analytical pure;
Described HA powder, purity are analytical pure;
The porosity of described support is 20%-70%, pore size 100 μ m-800 μ m.
The present invention is the preparation method by traditional powder metallurgy, utilizes the pore creating material method that obtains hole of volatilizing in sintering process to prepare osseous tissue engineering stephanoporate stent material.Use carbamide as pore creating material, with HA powder and high-purity magnesium or magnesium alloy powder (high-purity Mg-Zn alloy, high-purity Mg-Zn-Ca alloy, high-purity Mg-Zn-Ca-Fe alloy, high-purity Mg-Mn alloy, high-purity Mg-Zn-Mn alloy, above-mentioned alloy degree of purity all is not less than 99.99%.) in varing proportions ball milling mix powder, drum's speed of rotation 100r/min, about 6-10 of ball milling time hour, 100MPa pressurize 2-3min molding.Sintering is warming up to 150-200 ℃ earlier, insulation 4-5h; Be warming up to sintering temperature 300-600 ℃ (different and different) again according to each alloying component, insulation 2-4h, stove is cold.
For obtaining suitable adjustable mechanical property and corrosive nature, high-purity magnesium of the present invention and magnesium alloy powder are following material: high-purity magnesium, high-purity Mg-Zn alloy, high-purity Mg-Zn-Ca alloy, high-purity Mg-Zn-Ca-Fe alloy, high-purity Mg-Mn alloy, high-purity Mg-Zn-Mn alloy, above-mentioned alloy degree of purity all is not less than 99.99%.The alloying element of above-mentioned magnesium and magnesium alloy materials all is the necessary nutrients of human body, and its metabolite has no side effect to human body, can be human body and absorbs.By the porous magnesium bone tissue engineering stent material that above-mentioned magnesium and magnesium alloy materials are made, its density and human body bone density are approaching, and elastic modelling quantity and yield strength are compared with other metal materials near people's bone, can avoid or alleviate stress-shielding effect.Adopt the different one-tenth of above-mentioned material to be grouped into and to obtain adjustable mechanical property and corrosive nature, satisfy the requirement that human body different parts osseous tissue is implanted.
For strengthening the performance of the porous support that obtains, add HA (hydroxyapatite) powder of content 10%-20% (percent by volume) in the original material powder body of the present invention.HA has very low dissolubility as a kind of composition of nature bone in the human body environment.Cell is adsorbed onto on the porous magnesium support behind cultured and amplified in vitro, and along with the degraded gradually of support magnesium and magnesium alloy, cell continues the breeding growth, forms the new osseous tissue with vitality and correlation function with the residual HA that can't degrade.The distribution of HA in magnesium and magnesium alloy substrate and size have been improved the mechanical performance of porous support materials greatly, adjusting by its content and distribution, can make support obtain different mechanical performances, alleviate or avoid stress-shielding effect to adapt to the different mechanical properties of organism different parts bone.On the other hand, the interpolation of HA has reduced the increase of pH, has improved the cells survival environment, has improved the corrosion resistance of magnesium in normal saline and cell solution more to a certain extent.
For obtaining appropriate porosity and pore size, the present invention selects carbamide (CO (NH
2)
2) as pore creating material, be characterized in not absorbing moisture, be difficult for decomposing in room temperature, heating process is easy to decompose and do not react with timbering material, decomposes back noresidue in matrix.The volume ratio of pore creating material is 20%-70%.In this scope, the porosity of material of the present invention is 20%-70%, and pore size is also different with the different distributions scope of porosity, and the pore size overall range is at 100 μ m-800 μ m.The bone tissue engineering scaffold aperture size could provide desirable place for growing into of osseous tissue during greater than 150 μ m; Aperture size is basic demands of bone conduction greater than 200 μ m, and 200-400 μ m helps new bone growth most.After porosity surpassed 30%, hole can be interconnected, and is convenient to growing into of new bone tissue.Porosity is high more, helps growing into of new bone more.The pore size of porous magnesium timbering material of the present invention and porosity meet the material requirements of bone tissue engineering scaffold, are beneficial to the propagation procreation of osteocyte.
The specific embodiment
Below embodiments of the invention are elaborated: present embodiment has provided detailed embodiment being to implement under the prerequisite with the technical solution of the present invention, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
Selecting granular size for use is the pure magnesium powder of 200-300 purpose (purity 〉=99.99%), volume content 70%; The HA powder (analytical pure) of granular size<80 μ m, volume content 10%; Carbamide powder (analytical pure), volume content 20%.Adopt powder metallurgy and sintering process to obtain porosity and be about 20% porous magnesium bone tissue engineering scaffold.This material hole keeps circle or approximate ellipsoidal, and most of connection of hole distributes, and pore size is about 100 μ m-200 μ m.The about 28MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.14 milligram/month.
Embodiment 2
Selecting granular size for use is the high-purity Mg-Zn-Ca alloyed powder of 200-300 purpose (purity 〉=99.99%), volume content 60%; The HA powder (analytical pure) of granular size<80 μ m, volume content 10%; Carbamide powder (analytical pure), volume content 30%.Adopt powder metallurgy and sintering process to obtain porosity and be about 30% porous magnesium bone tissue engineering scaffold.This material void shape is better, keeps circle or approximate ellipsoidal, and most of connection of hole distributes, and pore size is about 150 μ m-300 μ m.The about 19.5MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.22 milligram/month.
Embodiment 3
Adopt the granular size high-purity Mg-Mn alloyed powder of 200-300 purpose (purity 〉=99.99%) volume content 50%; The HA powder (analytical pure) of granular size<80 μ m, volume content 15%; Carbamide powder (analytical pure), volume content 35%.Adopt powder metallurgy and sintering process to obtain porosity and be about 35% porous magnesium bone tissue engineering scaffold.This material hole keeps circle or approximate ellipsoidal, and most of connection of hole distributes, and pore size is about 150 μ m-400 μ m.The about 16.2MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.25 milligram/month.
Embodiment 4
Selecting granular size for use is the high-purity Mg-Zn alloyed powder of 200-300 purpose (purity 〉=99.99%), volume content 40%; The HA powder (analytical pure) of granular size<80 μ m, volume content 10%; Carbamide powder (analytical pure), volume content 50%.Adopt powder metallurgy and sintering process to obtain porosity and be about 50% porous magnesium bone tissue engineering scaffold.This material hole is an oblong, and hole is big and be communicated with distribution, and pore size is about 200 μ m-500 μ m.The about 6.5MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.35 milligram/month.
Embodiment 5
Adopt the granular size high-purity Mg-Zn-Ca-Fe alloyed powder of 200-300 purpose (purity 〉=99.99%) volume content 20%; The HA powder (analytical pure) of granular size<80 μ m, volume content 20%; Carbamide powder (analytical pure), volume content 60%.Adopt powder metallurgy and sintering process to obtain porosity and be about 50% porous magnesium bone tissue engineering scaffold.This material hole is an oblong, and hole is big and be communicated with distribution, and pore size is about 300 μ m-600 μ m.The about 12.2MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.30 milligram/month.
Embodiment 6
Adopt the granular size high-purity Mg-Zn-Mn alloyed powder of 200-300 purpose (purity 〉=99.99%) volume content 20%; The HA powder (analytical pure) of granular size<80 μ m, volume content 10%; Carbamide powder (analytical pure), volume content 70%.Adopt powder metallurgy and sintering process to obtain porosity and be about 70% porous magnesium bone tissue engineering scaffold.This material hole is an oblong, and hole is big and be communicated with distribution, and pore size is about 600 μ m-800 μ m.The about 3.2MPa of compression yield strength, can be in biological fluid or blood environment degraded and absorbed, degradation speed is about 0.60 milligram/month.