CN104353124B - A kind of 3D of composite magnetic nano material prints porous metals support and preparation method thereof - Google Patents
A kind of 3D of composite magnetic nano material prints porous metals support and preparation method thereof Download PDFInfo
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Abstract
The 3D that the invention discloses a kind of composite magnetic nano material prints porous metals support and preparation method thereof.This compound porous metal rack is by porous metals support and be positioned at the three-dimensional micro rack that its inside is prepared from by magnetic particle and natural macromolecular material, bioceramic and form.Magnetic particle, natural macromolecular material, bioceramic are injected porous metals brace aperture after being prepared into coagulant liquid by the present invention, and the 3D being prepared into composite magnetic nano material by freeze drying process prints porous metals support.The 3D of composite magnetic nano material of the present invention prints reparation and treatment that porous metals support may be used for the Cranial defect of bulk weight bearing area clinically.
Description
Technical field
The invention belongs to field of biomedical materials, the 3D relating to a kind of composite magnetic nano material prints porous metals support and preparation method thereof, is specifically related to a kind ofly be compounded with porous metals support of the three-dimensional micro rack be made up of bioceramic material, natural macromolecular material, magnetic particle and preparation method thereof.
Background technology
The Cranial defect caused due to disease and wound is commonly encountered diseases clinically, is also one of global problem of orthopaedics therapy, drastically influence the quality of life of patient.At present, the method for the treatment of Cranial defect has autologous bone and allogenic bone transplantation, degradable biomaterial and medical metal material to transplant, and tissue engineering technique etc.Though autologous bone is good, limited source, and unnecessary secondary insult can be brought to patient; There is again immunogenicity and the shortcoming such as pathogenic in allograph bone; Degradable biomaterial there has been clinically apply more widely because having good biocompatibility, but owing to lacking enough mechanical strengths, can only be applied among a small circle, the treatment of non-weight bearing area Cranial defect; On a large scale, the treatment of weight bearing area bone, articular defect can only adopt the transplanting of metal material clinically, although medical metal material has good biocompatibility, but shortage biological activity, and the elastic modelling quantity of metal material is far above body bone tissue, therefore, postoperatively occurred various complication, therapeutic effect is not ideal enough.Although tissue engineering technique is more advanced, and start to apply gradually clinically, the bone repair that at present tissue engineering technique builds still lacks enough mechanical strengths, is not suitable on a large scale, the reparation of weight bearing area Cranial defect.Therefore, research and develop a kind of new type bone repair materials, make the elastic modelling quantity that it had both had desirable mechanical strength and had matched with body bone tissue, possess again the superior bio performance of degradable biomaterial, for improving on a large scale, the late result of weight bearing area bone defect healing has important scientific meaning and practical value.
At present, rapid shaping technique 3 D-printing is widely used in the preparation of personalized bone renovating bracket material, is the product of the multi-crossed disciplines development such as biomedicine, material science and Modern Manufacturing Technology, can meets the urgent needs of clinical treatment.The brute force of 3 D-printing bone tissue engineering scaffold is comparatively large, closer to the mechanical property of nature bone.The method shortens the construction cycle effectively, reduces R & D Cost, and it accurately customizes can meet the difform bone defect healing of different parts, has unique advantage in prepared by the bone support of complex character.The bone tissue engineering scaffold of arbitrary shape size can be prepared fast according to the requirement of patient's personalization.But existing 3 D-printing bone tissue engineering scaffold is due to the restriction of printing technique, its structure yardstick meticulousr again cannot imitate the structure of nature bone, and aperture size is excessive cannot provide necessary attachment sites to make tissue be difficult to internal stent of growing into.
Summary of the invention
In order to solve deficiency of the prior art, a kind of 3D of composite magnetic nano material is the object of the present invention is to provide to print porous metals support.The 3D printing porous metals support of described composite magnetic nano material had both overcome porous metals support and had lacked bioactive defect, overcame Biodegradable material mechanical strength simultaneously and caused the defect that range of application is little not.The 3D printing porous metals support of composite magnetic nano material of the present invention can be used for reparation and the treatment of the large segmental bone defect of weight bearing area clinically.In addition, the 3D that the present invention also aims to provide a kind of above-mentioned composite magnetic nano material prints the preparation method of porous metals support.
To achieve these goals, present invention employs following technical scheme:
The 3D that the invention provides a kind of composite magnetic nano material prints porous metals supports, and described compound porous metal rack is by porous metals support and be positioned at the three-dimensional micro rack that described porous metals internal stent is made up of magnetic particle, natural macromolecular material, bioceramic and form.It is 50-100 μm that the 3D of composite magnetic nano material of the present invention prints porous metals support average pore size.
Preferably, the mass ratio of described magnetic particle and natural macromolecular material is 1-20:1.5-20; More preferably, the mass ratio of described magnetic particle and natural macromolecular material is 5:3-5.
Preferably, the mass ratio of described natural macromolecular material and bioceramic is 4:1-4.
Further, porous metals support of the present invention can be porous titanium alloy support, porous pure titanium support, porous stainless steel bracket, porous cobalt alloy support.In specific embodiment of the invention scheme, described porous metals support is porous titanium alloy support.
Further, the natural macromolecular material that the present invention uses can be one or more in collagen, gelatin, fibroin albumen, zein, alginate, chitosan, hyaluronate sodium, sodium alginate, dextran sulfate, heparin sodium, chondroitin sulfate or keratan sulfate.In specific embodiment of the invention scheme, described natural macromolecular material is gelatin.
Further, the bioceramic that the present invention uses can be one or more in nanometer hydroxyapatite, tricalcium phosphate or calcium phosphate.In specific embodiment of the present invention, described bioceramic is nanometer hydroxyapatite.Preferably, the diameter of described nanometer hydroxyapatite is 20nm.
Further, the magnetic particle that the present invention uses is γ-Fe
2o
3or Fe
3o
4.
The 3D that present invention also offers a kind of composite magnetic nano material prints the preparation method of porous metals support, and described preparation method comprises the following steps:
(1) porous metals support is prepared;
(2) mixed liquor of magnetic particle, natural macromolecular material, bioceramic is prepared;
(3) in the porous metals support mixed liquor implantation step (1) that step (2) obtains obtained;
(4) the porous metals support that step (3) obtains is immersed in mixed liquor prepared by step (2), places 4 DEG C of refrigerators freezing;
(5) take out above-mentioned freezing rear gel piece, strike off the unnecessary gel of porous metals rack surface, add in 0.1mol/L glycine solution and soak, then soak with deionized water, clean;
(6) take out the handled thing of step (5), put into vacuum freeze drier, lyophilization, namely obtain compound porous metal rack according to claim 1.
The technology that can be used for preparing porous metals support in prior art comprises Selective Laser Sintering (SLS), selective laser fusion technology (SLM), electron beam melting technology (EBM), porous metals support aperture prepared by above-mentioned technology is 100 μm-2000 μm, and elastic modelling quantity is less than 10GPa.The technology preparing porous metals also comprises the 3D printing technique of the present invention's use.The appearance that 3D prints can make full use of intensity and the plasticity of metal, by the process of the scan-datas such as CT, is built by Computer Design, and the personalized porous that metallic print can be become meet demand is communicated with labyrinth.Not only provide space to Bone Ingrowth, also because loose structure reduces the elastic modelling quantity of metal material, achieve and the mating of normal bone tissues elastic modelling quantity.
In specific embodiment of the invention scheme, the concrete operations of step (1) are as follows:
A, CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 100-1000 μm, aperture is 300-3000 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model;
B, employing EOSM280 metal material 3D printer, print porous metals support according to designing a model.
Preferably, the average Kong Zhuwei 300 μm of the 3-D view of targeted bony tissue, aperture are 1000 μm.
In specific embodiment of the invention scheme, the concrete operation step of step (2) is as follows:
A, natural macromolecular material being added in deionized water, make its final concentration be 1.5-20%w/v, under 37 DEG C of conditions, using magnetic stirring apparatus 300r/min to stir 2h to thoroughly dissolving; Preferably, the final concentration of natural macromolecular material is 3-5%w/v;
B, bioceramic and magnetic particle are joined in natural macromolecular material solution, wherein, the mass ratio of bioceramic and natural macromolecular material is 1-4:4, the mass ratio of magnetic particle and natural macromolecular material is 1-20:1.5-20, uses nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
Preferably, in above-mentioned steps b, the mass ratio of magnetic particle and natural macromolecular material is 5:3-5.
In specific embodiment of the invention scheme, the concrete operation step of step (3) is as follows: joined by cross-linking agent in mixed liquor prepared by step (2), stir, in the porous metals support that the mixed liquor implantation step (1) adding cross-linking agent is prepared.
Preferably, in above-mentioned mixed liquor, the final concentration of cross-linking agent is 0.1-1%v/v; More preferably, in above-mentioned mixed liquor, the final concentration of cross-linking agent is 0.65%v/v.
The cross-linking agent that the present invention uses can be one or more in 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride/N-hydroxy-succinamide, genipin, ethanol, glutaraldehyde.In specific embodiment of the invention scheme, cross-linking agent selects concentration to be glutaraldehyde solution or 1-(3-the dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride/N-hydroxy-succinamide solution of 25%v/v.
Preferably, described in step (4), 4 DEG C of refrigerator freezing times are 12h.
In specific embodiment of the invention scheme, the detailed step of step (5) is as follows: take out gel piece prepared by step (4), strike off the unnecessary gel of porous metals rack surface, add in 0.1mol/L glycine solution and soak 2h, soak with deionized water, clean 3 times again, need 4h altogether.
In specific embodiment of the invention scheme, the detailed step of step (6) is as follows: the handled thing taking out step (5), put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining composite magnetic nano material of the present invention prints porous metals support.
Alternatively, the 3D of composite magnetic nano material step (6) prepared prints porous metals supports and puts into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
In specific embodiment of the invention scheme, the porous metals support prepared in above-mentioned preparation method take titanium alloy as porous titanium alloy support prepared by raw material.
Preferably, the described bioceramic used in above-mentioned preparation method is nanometer hydroxyapatite.
Preferably, the described natural macromolecular material used in above-mentioned preparation method is gelatin.
Preferably, the described magnetic particle used in above-mentioned preparation method is γ-Fe
2o
3or Fe
3o
4.
Magnetic effect has been proved has obvious regulating and controlling effect to mescenchymal stem cell and osteoblast differentiation, significantly can strengthen the secretion of bone matrix and accelerate the process of skeletonization.On this basis, superparamagnetic nanoparticle is introduced 3D and is printed in micro rack inner between porous metals by the present invention, preparation has the bioactive bracket of superparamagnetic response, and exogenous magnetostatic field or low frequency pulsed magnetic fields are applied to it, increase its bone-forming effect, thus realize the life of inactive support.Effectively avoid various bioactie agent, the ectopic ossification that such as BMP (bone morphogenetic protein(BMP)) easily causes, the dissolving of excessive concentrations bone, antimicrobial activity forfeiture, slow release are difficult to demand problems such as mating.
In actual applications, externally-applied magnetic field can select magnetostatic field, and (intensity is at 0.5mT-3T, intermediate value is at 200-400mT), (its intensity is generally at 10-100mT can also to use low frequency pulsed magnetic fields, frequency is at 1-100Hz, intermediate value is 30mT, 15Hz) etc., intervene around fracture or Cranial defect.
Advantage of the present invention and beneficial effect:
(1) 3D of composite magnetic nano material of the present invention prints porous metals support and can provide optimal cell growth environment, the design having abandoned metal rack in traditional view must meet the restriction in the most applicable Growth of Cells aperture, be prepared into macroscopic void and high porosity structure as far as possible, thus achieved the maximization of the minimized of metal and Bone Ingrowth amount; Interior three-dimensional micro rack is then no longer by the restriction first meeting mechanical strength, adopt the material being beneficial to osteogenesis most as far as possible, build short texture, there is cell recognition site, be applicable to the three-dimensional bionic micro rack that cell seeks connections with growth, for cell offers the best growth microenvironment, thus the mutual supplement with each other's advantages both realizing.
(2) 3D of composite magnetic nano material of the present invention prints porous metals supports and provides and a kind ofly both had the bone renovating material that strong mechanical strength has strong biological activity simultaneously, this bone renovating material not only may be used for the injury repairing of cartilage but also can be used for reparation and the treatment of weight bearing area large segmental bone defect, extends the range of application of the bone renovating material existed in prior art.
(3) the invention using magnetic particle as composite, magnetic nano-particle has magnetic responsiveness and superparamagnetism, can assemble and locate, electromagnetic wave absorption heat production under alternating magnetic field under stationary magnetic field.Because magnetic nano-particle has the ability combined with cell surface, this just makes under the condition of externally-applied magnetic field, control and regulate the function of cell to become possibility.Under the effect of externally-applied magnetic field, magnetic nano-particle significantly can promote the propagation of mesenchymal stem cells MSCs.And human mesenchymal stem cell has and is divided into osteoblast, the ability of adipose cell and chondrocyte under the effect of magnetic nano-particle and externally-applied magnetic field, magnetic nano-particle and magnetic field synergy can promote Bone Defect Repari.
Accompanying drawing explanation
Fig. 1 shows porous and is communicated with three-dimensional digital model;
Fig. 2 shows the porous titanium alloy support that 3D prints;
Fig. 3 shows the electron-microscope scanning picture of the 3D printing porous metals support of composite magnetic nano material.
Concrete embodiment
Below in conjunction with specific embodiment, setting forth the present invention further, only for explaining the present invention, and can not limitation of the present invention be interpreted as.
The experimental technique of unreceipted actual conditions in the following example, the usually conveniently conditioned disjunction condition examinations of advising according to manufacturer.
The reagent in unreceipted source in the following example, all can obtain from commercial routes.
The 3D of embodiment 1 composite magnetic nano material prints the preparation of porous metals support
1, the preparation of porous titanium alloy support
(1) CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 100 μm, aperture are 300 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model (as shown in Figure 1).
(2) adopting EOSM280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) for raw material, printing porous titanium alloy support (as shown in Figure 2) according to designing a model.
2, the preparation of the mixed liquor of magnetic particle, natural macromolecular material, bioceramic
(1) gelatin particle of 1.5%w/v is added in deionized water soak 2h, simultaneously at 37 DEG C, under the magnetic stirring apparatus effect of 300r/min, be stirred to thorough dissolving.
(2) by nanometer hydroxyapatite powder nHA (diameter 20nm) and γ-Fe
2o
3join in gelatin solution, wherein the mass ratio of nHA and gelatin is 1:4, γ-Fe
2o
3be 1.5:1 with the mass ratio of gelatin, use nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
3, be that the glutaraldehyde solution of 25%v/v adds in above-mentioned mixed liquor as cross-linking agent with concentration, glutaraldehyde final concentration is 0.1%v/v, after stirring 15s, entering with syringe vasopressing injection the 3D prepared prints in porous titanium alloy support, and porous titanium alloy support is immersed in mixed liquor, place 4 DEG C of refrigerator 12h.
4, take out above-mentioned freezing rear gel piece, strike off POROUS TITANIUM excess surface gel, add in 0.1mol/L glycine solution and soak 2h, simultaneously under 37 DEG C of conditions, use the magnetic stirrer of 300r/min, same to method, soak with deionized water, clean 3 times again, about need 4h.
5, above-mentioned handled thing is put into container, adding deionized water to not having porous titanium alloy rack upper surface, putting into-80 DEG C of refrigerator freezing 4h.
6, take out frozen thing, put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining having bionic three-dimensional micro rack prints porous titanium alloy support (as shown in Figure 3).
7, above-mentioned support is put into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
The 3D of embodiment 2 composite magnetic nano material prints the preparation of porous metals support
1, the preparation of porous titanium alloy support
(1) CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 300 μm, aperture are 1000 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model (as shown in Figure 1).
(2) adopting EOSM280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) for raw material, printing POROUS TITANIUM support (as shown in Figure 2) according to designing a model.
2, the preparation of the mixed liquor of magnetic particle, natural macromolecular material, bioceramic
(1) gelatin particle of 3%w/v is added in deionized water soak 2h, simultaneously at 37 DEG C, under the magnetic stirring apparatus effect of 300r/min, be stirred to thorough dissolving.
(2) by nanometer hydroxyapatite powder nHA (diameter 20nm) and γ-Fe
2o
3join in gelatin solution, wherein the mass ratio of nHA and gelatin is 1:2, γ-Fe
2o
3be 3:5 with the mass ratio of gelatin, use nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
3, be that the glutaraldehyde solution of 25%v/v adds in above-mentioned mixed liquor as cross-linking agent with concentration, glutaraldehyde final concentration is 0.65%v/v, after stirring 15s, entering with syringe vasopressing injection the 3D prepared prints in porous titanium alloy support, and porous titanium alloy support is immersed in mixed liquor, place 4 DEG C of refrigerator 12h.
4, take out above-mentioned freezing rear gel piece, strike off POROUS TITANIUM excess surface gel, add in 0.1mol/L glycine solution and soak 2h, simultaneously under 37 DEG C of conditions, use the magnetic stirrer of 300r/min, same to method, soak with deionized water, clean 3 times again, about need 4h.
5, above-mentioned handled thing is put into container, adding deionized water to not having porous titanium alloy rack upper surface, putting into-80 DEG C of refrigerator freezing 4h.
6, take out frozen thing, put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining having bionic three-dimensional micro rack prints porous titanium alloy support (as shown in Figure 3).
7, above-mentioned support is put into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
The 3D of embodiment 3 composite magnetic nano material prints the preparation of porous metals support
1, the preparation of porous titanium alloy support
(1) CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 1000 μm, aperture are 3000 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model (as shown in Figure 1).
(2) adopting EOSM280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) for raw material, printing POROUS TITANIUM support (as shown in Figure 2) according to designing a model.
2, the preparation of the mixed liquor of magnetic particle, natural macromolecular material, bioceramic
(1) gelatin particle of 5%w/v is added in deionized water soak 2h, simultaneously at 37 DEG C, under the magnetic stirring apparatus effect of 300r/min, be stirred to thorough dissolving.
(2) by nanometer hydroxyapatite powder nHA (diameter 20nm) and γ-Fe
2o
3join in gelatin solution, wherein the mass ratio of nHA and gelatin is 1:2, γ-Fe
2o
3be 1:1 with the mass ratio of gelatin, use nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
3, be that the glutaraldehyde solution of 25%v/v adds in above-mentioned mixed liquor as cross-linking agent with concentration, glutaraldehyde final concentration is 0.65%v/v, after stirring 15s, entering with syringe vasopressing injection the 3D prepared prints in porous titanium alloy support, and porous titanium alloy support is immersed in mixed liquor, place 4 DEG C of refrigerator 12h.
4, take out above-mentioned freezing rear gel piece, strike off POROUS TITANIUM excess surface gel, add in 0.1mol/L glycine solution and soak 2h, simultaneously under 37 DEG C of conditions, use the magnetic stirrer of 300r/min, same to method, soak with deionized water, clean 3 times again, about need 4h.
5, above-mentioned handled thing is put into container, adding deionized water to not having porous titanium alloy rack upper surface, putting into-80 DEG C of refrigerator freezing 4h.
6, take out frozen thing, put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining having bionic three-dimensional micro rack prints porous titanium alloy support (as shown in Figure 3).
7, above-mentioned support is put into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
The 3D of embodiment 4 composite magnetic nano material prints the preparation of porous metals support
1, the preparation of porous titanium alloy support
(1) CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 100 μm, aperture are 300 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model (as shown in Figure 1).
(2) adopting EOSM280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) for raw material, printing POROUS TITANIUM support (as shown in Figure 2) according to designing a model.
2, the preparation of the mixed liquor of magnetic particle, natural macromolecular material, bioceramic
(1) gelatin particle of 20%w/v is added deionized water, at 37 DEG C, in the magnetic stirring apparatus of 300r/min, 2h is to thoroughly dissolving.
(2) by nanometer hydroxyapatite powder nHA (diameter 20nm) and Fe
3o
4join in gelatin solution, wherein the mass ratio of nHA and gelatin is 1:1, Fe
3o
4be 1:1 with the mass ratio of gelatin, use nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
3, be that the glutaraldehyde solution of 25%v/v adds in above-mentioned mixed liquor as cross-linking agent with concentration, glutaraldehyde final concentration is 1%v/v, after stirring 15s, entering with syringe vasopressing injection the 3D prepared prints in porous titanium alloy support, and porous titanium alloy support is immersed in mixed liquor, place 4 DEG C of refrigerator 12h.
4, take out above-mentioned freezing rear gel piece, strike off POROUS TITANIUM excess surface gel, add in 0.1mol/L glycine solution and soak 2h under 37 DEG C of magnetic stirring apparatus 300r/min effect, same to method, then soak with deionized water, clean 3 times, about need 4h.
5, above-mentioned handled thing is put into container, adding deionized water to not having porous titanium alloy rack upper surface, putting into-80 DEG C of refrigerator freezing 4h.
6, take out frozen thing, put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining having bionic three-dimensional micro rack prints porous titanium alloy support (as shown in Figure 3).
7, above-mentioned support is put into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
The 3D of embodiment 5 composite magnetic nano material prints the preparation of porous metals support
1, the preparation of porous titanium alloy support
(1) CT image is imported the three-dimensional imaging software such as Mimics or CAD, obtain the 3-D view of targeted bony tissue, average Kong Zhuwei 100 μm, aperture are 300 μm, with regular hexahedron, the filling of regular dodecahedron structural units, expand this image, obtain personalized porous and be communicated with three-dimensional digital model (as shown in Figure 1).
(2) adopting EOSM280 metal material 3D printer, with titanium alloy (Ti-6Al-4V) for raw material, printing POROUS TITANIUM support (as shown in Figure 2) according to designing a model.
2, the preparation of the mixed liquor of magnetic particle, natural macromolecular material, bioceramic
(1) gelatin particle of 20%w/v is added deionized water, at 37 DEG C, in the magnetic stirring apparatus of 300r/min, 2h is to thoroughly dissolving.
(2) by nanometer hydroxyapatite powder nHA (diameter 20nm) and Fe
3o
4join in gelatin solution, wherein the mass ratio of nHA and gelatin is 1:1, Fe
3o
4be 1:1 with the mass ratio of gelatin, use nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
3, be that 1-(3-the dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride/N-hydroxy-succinamide solution of 25%v/v adds in above-mentioned mixed liquor as cross-linking agent with concentration, 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride/N-hydroxy-succinamide final concentration is 1%v/v, after stirring 15s, entering with syringe vasopressing injection the 3D prepared prints in porous titanium alloy support, and porous titanium alloy support is immersed in mixed liquor, place 4 DEG C of refrigerator 12h.
4, take out above-mentioned freezing rear gel piece, strike off POROUS TITANIUM excess surface gel, add in 0.1mol/L glycine solution and soak 2h under 37 DEG C of magnetic stirring apparatus 300r/min effect, same to method, then soak with deionized water, clean 3 times, about need 4h.
5, above-mentioned handled thing is put into container, adding deionized water to not having porous titanium alloy rack upper surface, putting into-80 DEG C of refrigerator freezing 4h.
6, take out frozen thing, put into vacuum freeze drier ,-46 DEG C of lyophilization 48h, the 3D namely obtaining composite magnetic nano material prints porous metals support (as shown in Figure 3).
7, above-mentioned support is put into Epoxyethane sterilizing box and carry out sterilizing, independent subpackage process.
Those having ordinary skill in the art will appreciate that: can carry out multiple change, amendment, replacement and modification to these embodiments when not departing from principle of the present invention and aim, scope of the present invention is by claim and equivalents thereof.
Claims (15)
1. the 3D of a composite magnetic nano material prints porous metals support, it is characterized in that, the 3D of described composite magnetic nano material prints porous metals support by porous metals support be positioned at the three-dimensional micro rack that described porous metals internal stent is made up of magnetic particle, natural macromolecular material, bioceramic and form; The mass ratio of described magnetic particle and natural macromolecular material is 1-20:1.5-20; The mass ratio of described natural macromolecular material and bioceramic is 4:1-4.
2. the 3D of composite magnetic nano material according to claim 1 prints porous metals support, and it is characterized in that, described porous metals support is porous titanium alloy support.
3. the 3D of composite magnetic nano material according to claim 1 prints porous metals support, and it is characterized in that, described natural macromolecular material is gelatin.
4. the 3D of composite magnetic nano material according to claim 1 prints porous metals support, and it is characterized in that, described bioceramic is nanometer hydroxyapatite.
5. the 3D of composite magnetic nano material according to claim 1 prints porous metals support, and it is characterized in that, described magnetic particle is γ-Fe
2o
3or Fe
3o
4.
6. the 3D of the composite magnetic nano material according to any one of claim 1-5 prints the preparation method of porous metals support, and it is characterized in that, described preparation method comprises the following steps:
(1) porous metals support is prepared;
(2) mixed liquor of magnetic particle, natural macromolecular material, bioceramic is prepared;
(3) in the porous metals support mixed liquor implantation step (1) that step (2) obtains obtained;
(4) the porous metals support that step (3) obtains is immersed in mixed liquor prepared by step (2), places 4 DEG C of freezing 12h of refrigerator;
(5) take out above-mentioned freezing rear gel piece, strike off the unnecessary gel of porous metals rack surface, add in 0.1mol/L glycine solution and soak, then soak with deionized water, clean;
(6) take out the handled thing of step (5), put into vacuum freeze drier, lyophilization, the 3D namely obtaining described composite magnetic nano material prints porous metals support.
7. preparation method according to claim 6, is characterized in that, the concrete operation step of step (2) is as follows:
(1) natural macromolecular material being added in deionized water, make its final concentration be 1.5-20%w/v, under 37 DEG C of conditions, using magnetic stirring apparatus 300r/min to stir 2h to thoroughly dissolving;
(2) bioceramic and magnetic particle are joined in natural macromolecular material solution, wherein, the mass ratio of bioceramic and natural macromolecular material is 1-4:4, the mass ratio of magnetic particle and natural macromolecular material is 1-20:1.5-20, uses nanometer ultrasonic cell disruptor to break up mixture to homogenizing state.
8. preparation method according to claim 6, it is characterized in that, the concrete operation step of step (3) is as follows: added by cross-linking agent in mixed liquor prepared by step (2), stir, in the porous metals support that the mixed liquor implantation step (1) adding cross-linking agent is prepared.
9. preparation method according to claim 6, it is characterized in that, the detailed step of step (5) is as follows: take out gel piece prepared by step (4), strike off the unnecessary gel of porous metals rack surface, add in 0.1mol/L glycine solution and soak 2h; Soak with deionized water, clean 3 times again, need 4h altogether.
10. preparation method according to claim 6, it is characterized in that, the detailed step of step (6) is as follows: the handled thing taking out step (5), put into vacuum freeze drier,-46 DEG C of lyophilization 48h, the 3D namely obtaining described composite magnetic nano material prints porous metals support.
11. preparation methoies according to any one of claim 6-10, it is characterized in that, described porous metals support is porous titanium alloy support.
12. preparation methoies according to any one of claim 6-10, it is characterized in that, described bioceramic is nanometer hydroxyapatite.
13. preparation methoies according to any one of claim 6-10, it is characterized in that, described natural macromolecular material is gelatin.
14. preparation methoies according to any one of claim 6-10, it is characterized in that, described magnetic particle is γ-Fe
2o
3or Fe
3o
4.
The 3D of the composite magnetic nano material according to any one of 15. claim 1-5 prints porous metals support and is preparing the application in tissue engineering bone renovation material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
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| CN105288752A (en) * | 2015-10-29 | 2016-02-03 | 深圳市第二人民医院 | Magnetic nanometer compound biological interface material and preparation method thereof |
| CN107233619A (en) * | 2017-07-14 | 2017-10-10 | 中国人民解放军第四军医大学 | A kind of Porous titanium bone implant material of functionalization and preparation method thereof |
| CN107715182A (en) * | 2017-09-18 | 2018-02-23 | 中国医学科学院北京协和医院 | A kind of preparation method and applications of 3D printing composite magnetic metallic support |
| CN107596453A (en) * | 2017-10-25 | 2018-01-19 | 中国医学科学院北京协和医院 | A kind of 3D printing composite magnetic metallic support and its application |
| CN107854726A (en) * | 2017-11-22 | 2018-03-30 | 中国医学科学院北京协和医院 | A kind of compound rest and its preparation method and application |
| CN114504681A (en) * | 2020-10-23 | 2022-05-17 | 中国医学科学院北京协和医院 | Metal bracket filled with magnetic composite material and preparation method thereof |
| CN114405501A (en) * | 2021-03-30 | 2022-04-29 | 南昌大学 | Batch preparation method and application of magnetic-drive self-stirring micro catalyst |
| CN114085097B (en) * | 2021-11-23 | 2022-12-02 | 华中科技大学 | Magnetoelectric coupling bracket for bone tumor treatment and preparation method thereof |
| CN115044092A (en) * | 2022-07-25 | 2022-09-13 | 深圳市第二人民医院(深圳市转化医学研究院) | Three-dimensional porous magnetic nano hydrogel and preparation method and application thereof |
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