CN100453124C - Tissue scaffold material with porous, layered, three-dimensional space multilevel structure and preparation method thereof - Google Patents
Tissue scaffold material with porous, layered, three-dimensional space multilevel structure and preparation method thereof Download PDFInfo
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- CN100453124C CN100453124C CNB2006100189625A CN200610018962A CN100453124C CN 100453124 C CN100453124 C CN 100453124C CN B2006100189625 A CNB2006100189625 A CN B2006100189625A CN 200610018962 A CN200610018962 A CN 200610018962A CN 100453124 C CN100453124 C CN 100453124C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及多孔、分层、三维空间多级结构组织支架材料及其制备方法。利用生物可吸收聚乳酸、聚乙醇酸及其共聚物、聚己内酯等和壳聚糖、硫酸软骨素、胶原、硫酸肝素、海藻酸钠、透明质酸等作为基体原料。制备方法是采用纳米自组装技术将壳聚糖、硫酸软骨素等具有正或负电荷的医用高分子材料组装到特定圆柱芯材表面，经真空干燥、冷冻干燥制成一种结构、尺寸、形状可调的高度仿生人体管状组织的支架材料。
The invention relates to a porous, layered, three-dimensional space multi-level structure tissue support material and a preparation method thereof. Bioabsorbable polylactic acid, polyglycolic acid and its copolymers, polycaprolactone, etc., and chitosan, chondroitin sulfate, collagen, heparan sulfate, sodium alginate, hyaluronic acid, etc. are used as matrix materials. The preparation method is to use nanometer self-assembly technology to assemble chitosan, chondroitin sulfate and other medical polymer materials with positive or negative charges on the surface of specific cylindrical core materials, and then vacuum-dry and freeze-dry to make a structure, size and shape. A height-adjustable biomimetic scaffold material for human tubular tissue.
Description
Technical field
The present invention relates to the tissue stent material of a kind of porous, layering, tri-dimensional multiple-grade structure based on the preparation of nanometer self-assembling technique.Be particularly related to and select to have good biocompatibility, biodegradability and biotic induce, widely used at home and abroad bio-medical material is prepared into porous, the layering of bionical human body tubular tissue, the organization bracket and the preparation method of tri-dimensional multiple-grade structure.
Background technology
Tissue engineering (tissue engineering) is that goalkeeper's cytobiology and materialogy combine and carry out new branch of science external or construct in vitro tissue or organ.When the seed cell with specific function (seed cell) and degradable biomaterial (biodegradable polymer) mix be incorporated in In vitro culture a period of time or implant after, along with degraded gradually, the absorption of the continuous propagation of seed cell, extracellular matrix secretion and biomaterial, final particular organization or the organ that form with normal configuration and function.The generation of tissue engineering technique is an innovation of surgical repair technology, its deep development might change the treatment pattern of tradition " with the repair in trauma wound ", surgical wound is transplanted from histoorgan with the sick treatment of decreasing moved towards the histoorgan manufacturing, realize a major transformation in surgical intervention field.
Tissue (as tissues such as nerve, blood vessel, esophagus, trachea, anuses) damage and damagedly clinically see that up to now, its therapeutic effect still can not be satisfactory more.It is important topic anxious to be researched and solved at present that excellent performance, the bionical artificial material of structure height are provided.The surface chemical structure and the configuration of surface structure that experimental results show that any material all can be used as bio signal, this class signal can be regulated the expression of human body attached cell functioning gene, the Stability Analysis of Structures of messenger ribonucleic acid, the synthetic and function of gene outcome effectively and specifically on molecular level, thereby produces " the inductivity biological effect of material " effectively.This type of biological effect has not only determined the safety of biomaterial, has also determined biomaterial to be used to rebuild the specificity of human body physiological function.This class material surface signal is that function is specific and extremely responsive to the regulating action of human body cell, i.e. appearance in can contact with material at cell in effective adjusting of gene level several hours.The research and development that is found to be biomaterial of this phenomenon has proposed brand-new requirement.
Ideal tissue stent material has bionical characteristics, be constituent should with extracellular matrix (the extracellular matrix of neurocyte synthesis secretion, ECM) composition is approaching to greatest extent, and its structure should be similar to human tissue structure, the regeneration that helps organizing.
Ideal tissue stent material should possess following condition: the 1. interior spatial structure micropore that should have orientation, be arranged in parallel.2. degradation in vivo and absorbed by body in time, promptly the degradation speed of material and metabolism infiltration rate should be complementary with the speed of regeneration and restoration, 3. have ideal structure: promptly have the hierarchical classification loose structure.4. should guarantee the nutrition supply that tissue repair is required: the somatomedin that the required growth of the adjusting played seed cell, differentiation and promotion tissue repair and tissue regeneration of damaged tissues regeneration promptly is provided.
Summary of the invention
The object of the present invention is to provide adjustable composite high-molecular tissue stent material of composition, aperture and size, the shape of porous, layering, tri-dimensional multiple-grade structure and preparation method thereof.
To achieve these goals, technical scheme of the present invention is: biology can be absorbed polylactic acid, chitosan, chondroitin sulfate, collagen, heparin sulfate, sodium alginate and hyaluronic acid as matrix material, utilize nanometer self-assembling technique, lyophilization and particular manufacturing craft to prepare the tissue stent material of porous, layering, tri-dimensional multiple-grade structure.
Major part is core and assembled material, and wherein comprise can be by aminating degradable medical macromolecular material and material modified for core: polylactic acid, polyglycolic acid (PGA) and copolymer (PLGA), polycaprolactone (PCL) etc.That assembled material comprises is natural, synthetic have good biocompatibility, degradable medical macromolecular materials with plus or minus electric charge: chitosan, chondroitin sulfate, collagen, heparin sulfate, sodium alginate and hyaluronic acid.
Its construction features is porous, layering, multi-polar structure, and each layer is distributed with hole, macropore or the micropore of even connection, and its structure and aperture are adjustable.
For realizing said structure, the present invention utilizes organic amine compound-diamine compound that core is carried out aminolysis reaction and makes the surperficial amino that has positive charge of introducing of core, carry out acidify with suitable acid solution then, just will have again, the assembled material of the anti-electric charge of negative is assembling in layer in order alternately, after finishing, assembling adopt different cryogenic temperatures to carry out freezing, or adopt cross-linking agent to carry out crosslinkedly can obtaining porous, layering, multi-polar structure, each layer is distributed with the hole of uniform connection, macropore or micropore, in core and assembled material, add the mould of porogen and the drilling of use energy, make its structure and aperture adjustable.
Concrete scheme of the present invention is as follows
A kind of tissue stent material comprises the outer assembled material of porous support core and core, is porous, layering, tri-dimensional multiple-grade structure, and each layer is distributed with the hole of even connection.
The core of this tissue stent material comprises and can be absorbed macromolecular material and material modified by the aminating biology of organic diamine chemical compound: polylactic acid, polyglycolic acid and copolymer thereof, polycaprolactone; That assembled material comprises is natural, synthetic have good biocompatibility, degradable medical macromolecular materials with plus or minus electric charge: chitosan, collagen, chondroitin sulfate, heparin sulfate, sodium alginate and hyaluronic acid.
Tissue stent material of the present invention, its assembling number of plies is 5～5000 layers, every layer thickness 1～100 nanometer; The aperture is 100～600 microns a macropore.
Tissue stent material of the present invention, its assembling number of plies is 5～5000 layers, every layer thickness 1～100 nanometer, the aperture is 1～100 micron a aperture.
Tissue stent material of the present invention, its assembling number of plies is 5～5000 layers, every layer thickness 1～100 nanometer, the aperture is the micropore of 1 nanometer～1000 nanometers.
The preparation method of tissue stent material of the present invention: earlier make porous support with core material polylactic acid or polyglycolic acid and copolymer thereof or polycaprolactone, then with the chitosan or the collagen that have positive charge, replace self assembly in layer in order at porous support core skin with chondroitin sulfate that has negative charge or heparin sulfate assembled material, repeat the assembling number of plies of self assembly step up to design, then quick freezing and vacuum freezing promptly obtain the tissue stent material of porous, layering, tri-dimensional multiple-grade structure.
The preparation process of tissue stent material of the present invention is:
The preparation of step 1, core: core material polylactic acid or polyglycolic acid and copolymer thereof or polycaprolactone are dissolved in organic solvent ethyl acetate or acetone or chloroform or 1, in the 4-dioxane, injection has the spininess mould, in drying at room temperature to constant weight, remove mould, change vacuum drying oven over to and be dried to constant weight, immerse ethanol and water volume ratio and be removal oils and fats and impurity in 1: 1 solution, the abundant rinsing of water;
Step 2, aminating reaction: the core of step 1 preparation is immersed hexamethylene diamine-isopropyl alcohol, or ethylenediamine-isopropyl alcohol, or butanediamine-isopropyl alcohol, hexamethylene diamine-normal propyl alcohol, or ethylenediamine-normal propyl alcohol, or in butanediamine-normal propyl alcohol, carry out aminolysis reaction, remove unreacted hexamethylene diamine, ethylenediamine with the abundant rinsing of deionized water, butanediamine is dried to constant weight in the room temperature vacuum drying oven;
Step 3, acidification reaction: the core behind step 2 aminolysis in acidify in 0.02 mol hydrochloric acid solution under the room temperature, is washed to remove the hydrochloric acid of absorption with tri-distilled water;
Step 4, layer upon layer electrostatic self assembly: the core after step 3 acidify is soaked in chondroitin sulfate or heparin sulfate solution with absorption one deck chondroitin sulfate or heparin sulfate, and make the surface be with negative electricity, with the tri-distilled water flushing that contains 0.5 mol NaCl to remove unnecessary chondroitin sulfate or heparin sulfate. be immersed in then and soak in the acetic acid solution of chitosan or collagen that (its acetic acid solution is for containing acetic acid 2%, the aqueous solution that contains NaCl 0.2 mol), make the chitosan or the collagen of core surface adsorption one deck positively charged, wash with the acetic acid solution of mass concentration 0.6% earlier, this acetic acid solution contains NaCl 0.2 mol, reuse contains the tri-distilled water flushing of NaCl0.2 mol and removes unnecessary chitosan or collagen, repeat above-mentioned number of assembling steps 5～5000 times, prepare chondroitin sulfate or aminoacid-chitosan or collagen multilayer film;
Step 5, be assembled with chondroitin sulfate or heparin sulfate-chitosan or collagen multilayer film core with what step 4 made, immerse liquid nitrogen or put into cryogenic refrigerator cryogenic refrigeration rapidly, vacuum lyophilization promptly obtains the tissue stent material of porous, layering, tri-dimensional multiple-grade structure.
The aminating reaction of described preparation process 2, core is immersed the hexamethylene diamine-isopropyl alcohol of 0.07～0.1 grams per milliliter, or ethylenediamine-isopropyl alcohol, or butanediamine-isopropyl alcohol, hexamethylene diamine-normal propyl alcohol, or ethylenediamine-normal propyl alcohol, or in butanediamine-normal propyl alcohol, 37 ± 2 ℃ of reactions 2～3 hours, remove unreacted organic diamine chemical compound with the abundant rinsing of deionized water, in 20 ± 1 ℃ of vacuum drying ovens, dry to constant weight.
The acidification reaction of described preparation process 3, with the aminolysis core in acidify 1～2 hour in 0.02 mol hydrochloric acid solution under the room temperature, with the tri-distilled water flushing to remove the hydrochloric acid of absorption.
The layer upon layer electrostatic self assembly of described preparation process 4, the acidify core is soaked 30～60 minutes with absorption one deck chondroitin sulfate cellulose solution or heparin sulfate in the NaCl solution of sulfur acid chrondroitin solution or heparin sulfate 2-50 mg/ml, and make the surface be with negative electricity, NaCl concentration is 0.5 mol in the solution, washes 3 times to remove unnecessary chondroitin sulfate cellulose solution or heparin sulfate with the tri-distilled water that contains NaCl 0.5 mol; Be immersed in then in the mass concentration 1%-5% acetic acid solution of chitosan-containing or collagen 2～50 mg/ml and soaked 30～60 minutes, make the chitosan or the collagen of core surface adsorption one deck positively charged, be that 0.6% acetic acid solution is washed (acetic acid solution contains 0.2 mol NaCl) with mass concentration earlier, reuse contains the unnecessary chitosan or the collagen of tri-distilled water flushing removal of NaCl 0.2 mol.
Material assembling cryogenic temperature in the described preparation process 5 is-20 ± 0.5 ℃.
Description of drawings
Fig. 1, tissue stent material prepare the main technique flow process
Fig. 2, timbering material cross section multiple structure, pattern (AFM)
Fig. 3, timbering material loose structure, pattern (SEM)
Tissue stent material preparation technology of the present invention as shown in Figure 1, earlier medical macromolecular materials are dissolved in the organic solvent, inject mould, natural drying, make the organization bracket core, with this organization bracket core organic diamine chemical compound aminolysis, make the core surface introduce the amino that has positive charge, vacuum drying, use hcl acidifying then, make the acidify core, just will have again, the assembled material of the anti-electric charge of negative is assembling in layer in order, adopts different cryogenic temperatures to carry out lyophilization after assembling finishes, can obtain porous, layering, the tissue stent material of tri-dimensional multiple-grade structure
The specific embodiment
Test required main material and instrument
Chitosan (different deacetylation), polylactic acid (different molecular weight), polyglycolic acid (molecular weight 120,000), polycaprolactone, chondroitin sulfate, collagen, heparin sulfate, sodium alginate, hyaluronic acid, hexamethylene diamine, butanediamine, ethylenediamine, 1, the 4-dioxane, NaCl, hydrochloric acid, acetic acid, atomic force microscope (AFM) (scanning probe microscopy (SPM)), model: DI NanoscopeIV type, U.S. Wei Yike precision instrument company limited (Veeco, USA), the fourier transform infrared spectroscopy instrument, model: Nexus, the U.S. thermoelectric Buddhist nun's high-tensile strength company, FD-80 type vacuum freeze drier (Beijing rich doctor health instrument plant), digital camera, vacuum drying oven.
Embodiment 1
1. the preparation of timbering material
1. the preparation of core: with 3 grammes per square metre average molecular weights is that 30,000 polylactic acid is dissolved in 10 milliliter 1, in the 4-dioxane, injects on the mould, in drying at room temperature 24 hours, remove mould, change vacuum drying oven (20 ℃) over to and be dried to constant weight, immerse and remove oils and fats and impurity, the abundant rinsing of water in 1: 1 the alcohol-water;
2. aminating reaction: above-mentioned core is immersed in the hexamethylene diamine-isopropyl alcohol of 0.07 grams per milliliter, 37 ℃ of reactions 2 hours, unreacted hexamethylene diamine is removed in the abundant rinsing of water, dries to constant weight in 20 ℃ of vacuum drying ovens;
3. acidification reaction: with aminolysis PDLLA core in acidify 1 hour in 0.02 mol hydrochloric acid solution under the room temperature, with a large amount of tri-distilled waters flushings to remove the hydrochloric acid of absorption;
4. layer upon layer electrostatic self assembly: the acidify core is soaked 30 minutes with absorption one deck chondroitin sulfate in 0.5 mol NaCl solution of sulfur acid chrondroitin 2 mg/ml, and make the surface be with negative electricity, with the tri-distilled water flushing that contains 0.5 mol NaCl 3 times to remove chondroitin polysulfate. be immersed in then in 2% acetic acid solution of 2 mg/ml chitosans and soaked 30 minutes, make the chitosan of polylactic acid surface adsorption one deck positively charged; Wash with 0.6% acetic acid solution earlier, reuse contains the tri-distilled water flushing of 0.2 mol NaCl and removes unnecessary chitosan;
5. material assembling: repeat above-mentioned steps, can prepare the chondroitin sulfate-chitosan multilayer film of the desirable number of plies (10 layers) ,-20 ℃ are freezing, remove mould, lyophilization, promptly.
2. the composition of timbering material, pattern, structure and performance test
Utilize the fourier transform infrared spectroscopy instrument, model: Nexus, the U.S. thermoelectric Buddhist nun's high-tensile strength company, D/MAX-IIIA type x x ray diffractometer x: (Japanese Rikagu of science) and the S-450 of Hitachi type scanning electron microscope, U.S. Wei Yike scanning probe microscopy (SPM, DI Nanoscope IV type) (atomic force microscope, AFM)) observes the timbering material pattern.Experiment in vitro is that sample is placed phosphate buffer solution, measures the swellability and the degradability of material, the situation of change of pH value.
Scanning electron microscopic observation is less 3 nanometers that are about to the inner layer film aperture, and outer aperture is approximately 3 microns; Atomic force microscope observation timbering material cross section has tangible nanoscale stratiform structure, every layer even distribution of pores is arranged, layer and interlayer porosity communication, and the hole aperture is changed in stages.After implanting, prolong material degradation in time.Experiment in vitro is observed, and material at 15 days swelling takes place, 2 months profiles are complete, and the solution pH value changes small.
Embodiment 2
Method and the step identical with embodiment 1, but core adopts polyglycolic acid (molecular weight 120,000), self-assembled material adopts chondroitin sulfate and chitosan-collagen mixture to carry out material preparation, and assembling the number of plies is 20 layers, and-70 ℃ of refrigerators are freezing.
The atomic force microscope observation catheter section has tangible nanoscale stratiform structure, every layer even distribution of pores is arranged, layer and interlayer porosity communication, and the hole aperture is changed in stages.After implanting, prolong material degradation in time.Experiment in vitro is observed, and material at 15 days swelling takes place, 2 months profiles are complete, and the solution pH value changes small.
Scanning electron microscopic observation is less 3 nanometers that are about to the inner layer film aperture, and outer aperture is approximately 15 microns; The atomic force microscope observation catheter section has tangible nanoscale stratiform structure, every layer even distribution of pores is arranged, layer and interlayer porosity communication, and the hole aperture is changed in stages.After implanting, prolong material degradation in time.Experiment in vitro is observed, and material at 15 days swelling takes place, 2 months profiles are complete, and the solution pH value changes small.
Embodiment 3
Method and the step identical with embodiment 1, but core adopts polycaprolactone, self-assembled material adopts chondroitin sulfate and chitosan-collagen mixture to carry out material preparation, and assembling the number of plies is 200 layers, and-70 ℃ of refrigerators are freezing.
The atomic force microscope observation catheter section has tangible nanoscale stratiform structure, every layer even distribution of pores is arranged, layer and interlayer porosity communication, and the hole aperture is changed in stages.After implanting, prolong material degradation in time.Experiment in vitro is observed, and material at 15 days swelling takes place, 2 months profiles are complete, and the solution pH value changes small.
Scanning electron microscopic observation is less 3 nanometers that are about to the inner layer film aperture, and outer aperture is approximately 3500 nanometers; The atomic force microscope observation catheter section has tangible nanoscale stratiform structure, every layer even distribution of pores is arranged, layer and interlayer porosity communication, and the hole aperture is changed in stages.After implanting, prolong material degradation in time.Experiment in vitro is observed, and material at 15 days swelling takes place, 2 months profiles are complete, and the solution pH value changes small.
Claims (7)
1. self assembly tubular tissue timbering material, it is characterized in that, this tissue stent material comprises porous support core and the outer assembled material of core, be porous, layering, tri-dimensional multiple-grade structure, each layer is distributed with the hole of even connection, its support core comprises and can be absorbed macromolecular material and material modified polylactic acid thereof by the aminating biology of organic amine, polyglycolic acid and copolymer thereof, polycaprolactone, assembled material comprises natural, synthetic have a good biocompatibility, degradable medical macromolecular materials chitosan with plus or minus electric charge, collagen, chondroitin sulfate, heparin sulfate, sodium alginate, and hyaluronic acid, the assembled material number of plies is 5～5000 layers, every layer thickness 1～100 nanometer, the aperture is 100～600 microns a macropore, perhaps being 1～100 micron aperture, perhaps is the micropore of 1 nanometer～1000 nanometers.
2, the preparation method of the described self assembly tubular tissue of claim 1 timbering material, it is characterized in that, earlier make porous support with core material polylactic acid or polyglycolic acid and copolymer thereof or polycaprolactone, use assembled material chitosan or collagen then, replace self assembly in layer in order at porous support core skin with chondroitin sulfate or heparin sulfate, repeat the assembling number of plies of self assembly step up to design, then quick freezing and vacuum freezing promptly obtain the tissue stent material of porous, layering, tri-dimensional multiple-grade structure.
3, the preparation method of self assembly tubular tissue timbering material as claimed in claim 2 is characterized in that, preparation process is:
The preparation of step 1, core: core material polylactic acid or polyglycolic acid and copolymer thereof or polycaprolactone are dissolved in organic solvent ethyl acetate or acetone or chloroform or 1, in the 4-dioxane, injection has the spininess mould, in drying at room temperature to constant weight, remove mould, change vacuum drying oven over to and be dried to constant weight, immerse ethanol and water volume ratio and be removal oils and fats and impurity in 1: 1 solution, the abundant rinsing of water;
Step 2, aminating reaction: the core of step 1 preparation is immersed hexamethylene diamine-isopropyl alcohol, or ethylenediamine-isopropyl alcohol, or butanediamine-isopropyl alcohol, or hexamethylene diamine-normal propyl alcohol, or ethylenediamine-normal propyl alcohol, or in butanediamine-normal propyl alcohol, carry out aminolysis reaction, remove unreacted hexamethylene diamine with the abundant rinsing of deionized water, ethylenediamine or butanediamine are dried to constant weight in the room temperature vacuum drying oven;
Step 3, acidification reaction: the core behind step 2 aminolysis in acidify in 0.02 mol hydrochloric acid solution under the room temperature, is washed to remove the hydrochloric acid of absorption with tri-distilled water;
Step 4, layer upon layer electrostatic self assembly: the core after step 3 acidify is soaked in chondroitin sulfate or heparin sulfate solution with absorption one deck chondroitin sulfate or heparin sulfate, and make the surface be with negative electricity, wash to remove unnecessary chondroitin sulfate or heparin sulfate with the tri-distilled water that contains 0.5 mol NaCl, be immersed in then in the acetic acid solution of chitosan or collagen and soak, its acetic acid solution is the aqueous solution that contains acetic acid 2% and contain NaCl 0.2 mol, make the chitosan or the collagen of core surface adsorption one deck positively charged, wash with the acetic acid solution of mass concentration 0.6% earlier, reuse contains the tri-distilled water flushing of NaCl 0.2 mol and removes unnecessary chitosan or collagen, repeat above-mentioned number of assembling steps 5～5000 times, prepare chondroitin sulfate or heparin sulfate-chitosan or collagen multilayer film;
Step 5, be assembled with chondroitin sulfate or heparin sulfate-chitosan or collagen multilayer film core with what step 4 made, immerse liquid nitrogen or put into cryogenic refrigerator cryogenic refrigeration rapidly, vacuum lyophilization promptly obtains the tissue stent material of porous, layering, tri-dimensional multiple-grade structure.
4, the preparation method of self assembly tubular tissue timbering material as claimed in claim 3, it is characterized in that, the aminating reaction of described step 2, core is immersed the hexamethylene diamine-isopropyl alcohol of 0.07～0.1 grams per milliliter, or ethylenediamine-isopropyl alcohol, or butanediamine-isopropyl alcohol, or hexamethylene diamine-normal propyl alcohol, or ethylenediamine-normal propyl alcohol, or in butanediamine-normal propyl alcohol, 37 ± 2 ℃ of reactions 2～3 hours, remove unreacted organic diamine chemical compound with the abundant rinsing of deionized water, in 20 ± 1 ℃ of vacuum drying ovens, dry to constant weight.
5, the preparation method of self assembly tubular tissue timbering material as claimed in claim 3, it is characterized in that, the acidification reaction of described step 3, with the aminolysis core in acidify 1～2 hour in 0.02 mol hydrochloric acid solution under the room temperature, with the tri-distilled water flushing to remove the hydrochloric acid of absorption.
6, the preparation method of self assembly tubular tissue timbering material as claimed in claim 3, it is characterized in that, the layer upon layer electrostatic self assembly of described step 4, the acidify core is soaked 30～60 minutes with absorption one deck chondroitin sulfate cellulose solution or heparin sulfate in the NaCl solution of sulfur acid chrondroitin solution or heparin sulfate 2～50 mg/ml, and make the surface be with negative electricity, wash 3 times to remove unnecessary chondroitin sulfate cellulose solution or heparin sulfate with the tri-distilled water that contains NaCl 0.5 mol; Be immersed in then in mass concentration 2% acetic acid solution of chitosan-containing or collagen 2-50 mg/ml and soaked 30～60 minutes, make the chitosan or the collagen of core surface adsorption one deck positively charged, be that 0.6% acetic acid solution is washed with mass concentration earlier, reuse contains the unnecessary chitosan or the collagen of tri-distilled water flushing removal of NaCl 0.2 mol.
7, the preparation method of self assembly tubular tissue timbering material as claimed in claim 3 is characterized in that, the material assembling cryogenic temperature in the described step 5 is-20 ℃.
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| CNB2006100189625A CN100453124C (en) | 2006-04-28 | 2006-04-28 | Tissue scaffold material with porous, layered, three-dimensional space multilevel structure and preparation method thereof |
| PCT/CN2006/001027 WO2007124622A1 (en) | 2006-04-28 | 2006-05-19 | The 3d porous layered scaffold for tissue engineering and the preparation thereof |
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| CNB2006100189625A CN100453124C (en) | 2006-04-28 | 2006-04-28 | Tissue scaffold material with porous, layered, three-dimensional space multilevel structure and preparation method thereof |
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| CN101884808B (en) * | 2010-07-23 | 2016-02-03 | 中国人民解放军第三军医大学野战外科研究所 | The Acellular bone groundmass composite material of partially anti-freezing function and cell capture and preparation method |
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| CN102675678B (en) * | 2011-03-17 | 2014-04-16 | 中国医学科学院肿瘤研究所 | PCL (polycaprolactone)-g-PGMA (poly glyceryl methacrylate)/gelatin composite material and preparation method thereof |
| CN102675677B (en) * | 2011-03-17 | 2014-04-16 | 中国医学科学院肿瘤研究所 | Application of PCL-g-PGMA (polycaprolactone-graft-polyglycidyl methacrylate)/gelatin composite material in cell transfection |
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| CN104056302B (en) * | 2013-03-18 | 2016-12-28 | 杭州启迪生物科技有限公司 | A kind of for tissue engineering bracket material building bone graft and preparation method thereof |
| CN103861152B (en) * | 2014-03-12 | 2015-05-27 | 暨南大学 | Hierarchical porous chitosan/polylactic acid composite material and preparation method and application thereof |
| WO2017116355A1 (en) | 2015-12-29 | 2017-07-06 | Atilim Universitesi | Tissue scaffold with enhanced biocompatibility and mechanical properties and a method for producing it |
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