CN1376521A - High-molecule porous scaffold for tissue engineering and its preparing process by hot pressing - Google Patents
High-molecule porous scaffold for tissue engineering and its preparing process by hot pressing Download PDFInfo
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Abstract
A high-molecular porous scaffold for tissue engineering is prepared from biodegradable and biocompatible high-molecular material through designing flexibility-rigidity combined mould and hot press/particle infusion. Said process scaffold has complex shape similar to the damage tissue or organ and communicated porous structure. Its porosity is more than 90%.
Description
Technical field
The invention belongs to technical field of polymer materials and biomedical engineering field, be specifically related to a kind of used in tissue engineering extracellular matrix substitute-Biodegradable high-molecular porous support with defective tissue or the same complex appearance of organ and preparation method thereof that has.
Technical background
Organizational project is reproduced or the new method of repair tissue or organ with living cells as a kind of, overcome the donor deficiency of Therapeutic Method existence such as traditional tissue or organ transplantation and the problem of immunologic rejection, made the treatment of tissue or organ defect enter the New Times that organ is made from organ transplantation.The ultimate principle of organizational project and method are to have good biocompatibility with planting at the human body cell of In vitro culture and in vivo progressively on the tissue engineered porous scaffold of degraded and absorbed, form the cell-scaffold complex, cell is bred on support, is broken up, then with the sick position of decreasing of this complex implanting to human body tissue, continue propagation justacrine extracellular matrix in vivo, be accompanied by the progressively degraded of material, form new tissue and the organ that adapts with self function and form, repair sick purpose of decreasing tissue and organ thereby reach.At present, Tissue Engineering Study both domestic and external is from comprehensive expansion of various aspects such as cell differentiation and amplification, biomaterial and porous support (being the extracellular matrix substitute), tissue constructions, and the portion of tissue engineering product has entered clinical experimental stage.One of key technology of organizational project is the biomaterial with excellent biological compatibility and biodegradation absorbent properties is made the porous support of the specific three dimensional shape with similar defective tissue or organ.
Tissue engineered porous scaffold is made by Biodegradable high-molecular usually, and the problem that its preparation mainly contains two aspects needs to solve, i.e. loose structure of Xiang Lianing and suitable profile.Link to each other, porosity provides the place of cell adhesion, propagation, differentiation up to the loose structure more than 90%, obtains nutrition and oxygen, the passage of discharge metabolite and the place of vascularization.The main means that form loose structure have fibrous joints, porogen leaching, gas foaming, lyophilization (or thermic is separated), the pre-structure of tubulose pore passage structure and 3 D-printing rapid shaping.Wherein, the porogen solvent extraction method is simple, the suitability is wide, and porosity and hole dimension are easily regulated, be one than method in common (Mikos and Langer, Polymer, 1994,35 (5): 1068-1077).
The profile of support has then determined the shape and size of the tissue or the organ of final formation.The main means that form contoured cradle have offhand, mould molding and speed forming method, and mould molding comprises solvent cast, mold pressing, extrude and method such as injection moulding.The offhand method is simple, and it is convenient to use, and be the forming method of reporting the earliest in the document, but the gained shape is comparatively simple, and part accuracy is lower, and depends on technology (U.S.'s patent of invention 5514378 of operator; Biomaterials, 1993,14 (50): 323-330; J Biomed Mater Res, 53:1-7).Thomson (Biomaterials, 1998,19:1935-1943) and Gome (Biomaterials, 2001,22:883-889) adopt pressure sintering and injection to prepare porous support respectively, although the author points out this method and can be used for the preparation of complex-shaped support, only reported the result of simple shape support such as cylindrical or square in the literary composition.And use in organizational project more is the three-dimensional porous rack with complicated shape that is complementary with particular organization or organ, thereby the technology of preparing that research and development have a three-dimensional porous rack of complicated shape is the key issue that presses for solution in the Tissue Engineering Study.
In solvent casting method, the existence of a large amount of solvents makes macromolecule/solvent/porogen complex that good flowability be arranged, thereby can carry out cast molding, the porous support of preparation simple shape, but when complex-shaped, the thickness of preparation surpasses the porous support of 2mm, because of the equal unusual difficulty of solvent evaporates and the demoulding, do not appear in the newspapers in the document and adopt solvent casting method to prepare the support of complicated shape.On the other hand, often easily cause the formation of surperficial cortex when solvent casting method prepares porous support, the implantation of this pair cell in organizational project is used or the transmission of interior growth and nutrient substance and metabolite are all unfavorable.As improvement to solvent cast/particle solvent extraction method, the inventor once proposed a kind of new method-colding pressing/the particle solvent extraction method based on solvent for preparing used in tissue engineering degradable macromolecule porous support, the porous support prepared of method not only has continuous loose structure thus, rack surface also is a loose structure, avoided the formation of surperficial cortex, but the void density of rack surface is lower than body.Can improve the rack surface void density in view of reducing solvent load, we consider at first to adopt solvent casting method to obtain macromolecule, the porogen complex of mix homogeneously, adopt the flexibility-rigidity composite die of particular design, this not solvent-laden complex is carried out hot-forming, with have the used in tissue engineering high-molecule porous scaffold with defective tissue or organ same complex appearance of preparation rack surface void density near rack body.
Summary of the invention
The objective of the invention is to propose a kind of rack surface void density near internal stent, have used in tissue engineering Biodegradable high-molecular porous support with defective tissue or the same or similar complex appearance of organ and preparation method thereof.
The used in tissue engineering high-molecule porous scaffold with complicated shape that the present invention proposes has and defective tissue or the same complex appearance of organ, helps the final tissue of needs or the profile of organ of forming in organizational project is used.More than tissue or organ comprise external ear, nose, finger, toe, moral character, meniscus, cornea, bone etc.Its size and real human or animal's tissue or organ or its part are suitable, or scaled or amplification.For example, when preparation had the support of auricle, the cell consumption may be less when considering the tissue construction experiment, and the porous support size can be generally 1/5～1/2 of true tissue or organ size less than real human or animal's tissue or organ size.
The used in tissue engineering high-molecule porous scaffold that the present invention proposes with complicated shape, porosity is more than 50%, generally can reach more than 90%, reaches as high as more than 99%, and has the pore structure that is interconnected, the support endoporus is evenly distributed.Rack surface also is a loose structure, and surface pore density is near body or not obviously be lower than the body apertures gap density.
The used in tissue engineering high-molecule porous scaffold with complicated shape that the present invention proposes, range of aperture size is 10-900 μ m, is generally 90-450 μ m.
The used in tissue engineering high-molecule porous scaffold that the present invention proposes with complicated shape, can degrade in the physiological environment in vivo, degradation time can need and form and be adjusted according to time of tissue growth and reparation by macromolecular structure, the degradation time scope is 1 thoughtful 2 years, is generally 1 month to 6 months.
The used in tissue engineering high-molecule porous scaffold with complicated shape that the present invention proposes by the flexibility-rigidity composite die of particular design, adopts hot pressing/particle solvent extraction method preparation.Concrete steps are as follows:
1, tissue or organ model are made.At first modeling material is made into the shape of required defective tissue or organ, obtains the model of defective tissue or organ;
2, the design of flexibility-rigid die and manufacturing.Above-mentioned tissue or organ model are put into diaphragm capsule, will insert diaphragm capsule behind flexible die material and the firming agent mix homogeneously thereof, compacting is at room temperature solidified, and the demoulding obtains flexible die former A; A puts into diaphragm capsule with former, puts into above-mentioned tissue or organ model again, repeats said process and obtains former B; Simultaneously, design and processing metal rigid die make flexible die just can put into rigid die;
3, the preparation of macromolecule, porogen complex.Biodegradable high-molecular is dissolved in solvent orange 2 A, form macromolecular solution, add the porogen particle then, stir, gained paste-like mixture is cast on glass plate or the polyfluortetraethylene plate, make most of solvent evaporates final vacuum drying remove residual solvent A under the room temperature, obtain macromolecule/porogen complex, it is cut into strip or lamellar is standby;
4, flexible die A is put into rigid die, insert macromolecule/porogen complex, cover flexible die B, compress metal platen, put between two block pressur plates of press, be warming up to high molecular vitrification point or more than the fusing point, material is softening gradually and constantly be compacted, keep certain hour with abundant typing, demolding after cooling;
5, obtain having the solid support of the macromolecule/porogen complex of required form after the demoulding, put into beaker and leach the porogen particle with solvent B, treat that the porogen particle leaches fully after, the porous support that obtains wetting;
6, wet porous support is taken out from solvent B, remove solvent B, its method can be earlier with filter paper or toilet paper with most of solvent B sucking-off, vacuum drying to be to remove wherein residual solvent B then, obtains have the used in tissue engineering Biodegradable high-molecular porous support with defective tissue or organ same complex appearance of required rack surface void density near rack body.
The modeling material that is adopted when the present invention makes tissue or organ model comprises Gypsum Fibrosum, wax, timber, rigid plastics etc., and the making of tissue or organ model can be adopted and make by hand, also can adopt speed forming method to make.
The material that the present invention makes flexible die is the macromolecular elastomer material, comprises silastic material, thiorubber. material, polyether rubber material etc., is mainly silastic material.Used silastic material comprises polyaddition type silicone rubber and condensation polymer type silicone rubber.
The present invention makes the silicone elastomer material of flexible die and is made up of host and firming agent, and host and firming agent is even by suitable mixed, is filled into immediately in the diaphragm capsule, solidifies 2-30 minute under the room temperature, is generally 5-10 minute, and the demoulding promptly gets flexible die.The elasticity of flexible die can be regulated and control by the ratio of host and firming agent.The ratio of silicone rubber host and firming agent is 10: (0.2～1.5) is generally 10: (0.5～1.0).Silicone rubber has elasticity as mold materials and advantage such as resilience is good, stamp surfaces is bright and clean and clear, change in volume is little.
Diaphragm capsule used among the present invention is made by metal material or plastics, metal material comprises carbon steel, rustless steel, copper, aluminum or its alloy etc., and plastics comprise thermosetting plasticses such as thermoplastics such as polyvinyl chloride, politef, polypropylene, polymethyl methacrylate, Merlon and phenolic resins.Diaphragm capsule has enough rigidity to have enough dimensional accuracies to guarantee the flexible die that makes.
The used rigid die of the present invention is made by metal material, comprises carbon steel, rustless steel, copper, aluminum or its alloy etc.Rigid mould has enough mechanical strengths and the rigidity pressure when bearing molding.
The used in tissue engineering high-molecule porous scaffold with complicated shape that the present invention proposes adopts biodegradation, biocompatible polymer material preparation.Used macromolecular material comprises polyhydroxycarboxyliacid acid ester, poe, poly-anhydride or the copolymer be made up of them or blend etc.Above polyhydroxycarboxyliacid acid ester comprises poly-(D, L-lactic acid) (PDLLA), gathers (L-lactic acid) (PLLA), polyglycolic acid (PGA), polycaprolactone homopolymer and poly lactic coglycolic acid (PLGA), caprolactone copolymer or other copolymers such as (PCL).The compositing range of above PLGA copolymer, caprolactone copolymer or other copolymer is 3: 97～97: 3.Better choice comprises poly-(D, L-lactic acid), poly-(L-lactic acid), poly lactic coglycolic acid (LA: the GA compositing range is 50: 50～90: 10, as PLGA85: 15, PLGA75: 25).Polylactic acid, polyglycolic acid and the copolymer of the two by the U.S. FDA authentication, can be used in the clinical experiment, now have been successfully used to medical products such as suture, controlled drug delivery system.Above Biodegradable high-molecular all has excellent biological compatibility, implants reaction such as the repellency that can not cause inflammation in vivo.Above macromolecule is all degraded in the physiological environment in vivo, and its catabolite is low-molecular-weight chemical compounds such as lactic acid, hydroxyacetic acid, also has excellent biological compatibility, and can be absorbed and finally excrete by normal metabolic pathway.The degradation rate of above Biodegradable high molecular can be according to the time length of tissue growth and reparation, and by changing high molecular structure or form and adjusted, the degradation time scope is 1 thoughtful 2 years, is generally 1 month to 6 months.More than biodegradable polymeric molecular weight ranges be 10,000 to 3,000,000, be generally 30,000 to 200,000.
The used solvent of the present invention comprises solvent orange 2 A and solvent B.Require solvent orange 2 A solubilized macromolecule, but can not change high molecular structure and performance; Porogen is not dissolved, and do not change the character of porogen; Have suitable volatility, under vacuum condition, can remove fully.Solvent for use A comprises any or its mixture in chloroform, dichloromethane, the acetone, and only solvent is a chloroform.Solvent B solubilized porogen, but do not dissolve used macromolecule, also can not change high molecular character.Solvent B has suitable volatility, can remove fully under vacuum condition.Solvent B is generally tap water, pure water, deionized water, and better choice is a deionized water.
The used porogen of the present invention is the inorganic matter or the Organic substance particle of crystallization or amorphous, and the porogen particle is dissolved in solvent B but is insoluble to solvent orange 2 A.The porogen particle not with used macromolecule generation chemical reaction, and have excellent biological compatibility, remain in micro-porogen in the porous support to organism nonhazardous effect.Porogen not with high molecular weight reactive, also be insoluble to solvent orange 2 A, thereby can be scattered in the macromolecular solution equably and keep its shape and size, after it was by solvent B dissolving, the occupied volume of porogen just became hole, formed porous support.The pore structure of porous support and size determine by porogen shape, size and consumption.Used porogen particle comprises inorganic salt particle, polysaccharide, protein, synthetic high polymer and other organic micromolecule compound, or the mixture of being made up of them.The preferential sodium salt particle of selecting comprises sodium chloride, sodium citrate, sodium tartrate, and optimum selection is the sodium chloride particle.Particle sieves into different fractions with standard screen, and the grain size scope is 10-900 μ m, and the stock size scope is 90-450 μ m, and the optimum size scope is 125-450 μ m.
The used macromolecular solution concentration range of the present invention is 1wt%-50wt% (percentage by weight is based on the macromolecular solution total weight), and better concentration range is 8wt-20wt%.The porogen amount ranges is 50wt%-99wt% (based on macromolecule and a porogen total weight), and better amount ranges is 80wt%-95wt%; Corresponding macromolecule amount ranges is 50wt%-1wt%, and better amount ranges is 20wt%-5wt%.
Among the present invention, porogen particle dispersed with stirring in macromolecular solution, is formed finely dispersed paste-like macromolecule, solvent, porogen complex.This slurry has good flowability, it is cast on glass plate or the polyfluortetraethylene plate, make most of solvent evaporates final vacuum remove residual solvent A under the room temperature, obtain macromolecule/porogen complexes membrane, be cut into be filled into after strip or the lamellar carry out in the mould hot-forming.
Mould therefor of the present invention is the flexibility-rigidity composite die of particular design, and flexible die is enclosed within the rigid die, forms an integral body.Pressure when rigid die is born molding, flexible die directly contacts with molding object-macromolecule/porogen complex, relies on the shape of flexible die (former) inner surface to form contoured cradle.Flexible die is made by the cold curing cross-linked rubber, and making is simple, convenient, accurately the profile of duplicating model.The elasticity of flexible die and deformability can suitably be out of shape it when the demoulding, improve the release property of macromolecule, porogen complex support.
Among the present invention, hot-forming temperature is higher than macromolecule fusing point or vitrification point 5-100 ℃, generally is higher than macromolecule fusing point or vitrification point 10-50 ℃; Dwell time is 1-30 minute, is generally 5-10 minute.
Among the present invention, hot-press forming device adopts general purpose rubber vulcanizer or other hot-press equipment.
Among the present invention, in solvent B, leach porogen through macromolecule, the porogen complex support of hot-forming formation.Macromolecule/porogen complex support is put into beaker, add solvent B, solvent B consumption is excessive greatly, and its weight is generally macromolecule, solvent, porogen complex weight support frame 100-500 times, better selection 200-300 doubly changed one time solvent B every 2-8 hour.Whether the sodium chloride porogen leaches available silver nitrate solution check fully, is about to the aqueous solution that silver nitrate is made into 0.1mol/L, is added drop-wise in the leachate, as white precipitate occurs, shows that porogen does not leach fully, otherwise, show that porogen leaches fully.
Among the present invention, the wet support that leaches porogen fully removes most of solvent B with filter paper or toilet paper suction, carries out vacuum drying then, and the vacuum drying temperature generally is not higher than 50 ℃, be 4-48 hour drying time, depends on the content of drying condition and support internal solvent B.Remove fully and obtain have the used in tissue engineering high-molecule porous scaffold with defective tissue or organ same complex appearance of rack surface void density behind the solvent B near rack body.
The present invention has following characteristics:
1, the present invention adopts the flexibility-rigidity composite die of particular design, and rigid die provides bearing capacity, and flexible die provides the ability that accurately forms the support complex appearance and the smooth demoulding of support, hard and soft combination, and preparation process is easy, feasible.
2, the present invention adopts solvent casting method at first to prepare the macromolecule/porogen complex of mix homogeneously, and is then that macromolecule/porogen complex is hot-forming, leaches porogen at last.
When 3, the present invention prepares porous support molding object macromolecule/porogen complex is warming up to the macromolecule vitrification point or makes it obtain forming ability more than the fusing point, suitably lowering the temperature after the molding makes it have good shape hold facility.
4, the molding object of this method does not contain solvent, rack surface that the more important thing is preparation is a loose structure, avoided solvent cast, particle solvent extraction method easily to form the shortcoming of surperficial cortex, its surface pore density is higher than colding pressing/the particle solvent extraction method based on solvent, help the implantation or the interior growth of cell, the transmission of nutrition and metabolism thing.Thereby this method is different from solvent cast/particle solvent extraction method, also is different from based on the colding pressing/the particle solvent extraction method of solvent, can be described as hot pressing/particle solvent extraction method.
5, the high-molecule porous scaffold of the present invention's preparation has and defective tissue or the same or similar complex appearance of organ, helps the dummy by tissue engineering technique generation and defective tissue or the same profile of organ, reaches the purpose of repairing fully.
6, the high-molecule porous scaffold porosity of the present invention's preparation is up to more than 90%, and the hole is interconnected, and pore size distribution is even.
7, the high-molecule porous scaffold surface of the present invention's preparation is a loose structure, and the rack surface void density approaches internal stent.
8, the present invention adopts the good Biodegradable high-molecular of biocompatibility to make timbering material, is expected to the generation of toxic and side effects such as avoiding or diminish inflammation after implanting, and can meet biomedical requirement better.
9, the porogen that adopts of the present invention is soluble in water, easily from porous support, remove fully, and residual if any trace, because of sodium chloride is the necessary composition of human body, sucrose is one of energy source of human body, to the human body nonhazardous; And porogen is cheap and easy to get.
10, easy, feasible, the favorable reproducibility of porous support preparation method of the present invention's proposition helps large-scale production.
The transmission of nutrition and metabolism thing had been widely used in field of tissue engineering technology when 11, the porous support of the present invention preparation helped the implantation of cell and interior growth and cell culture.
Description of drawings
Fig. 1 is PCL people's ear shape porous support.
Fig. 2 is PCL people's ear shape porous support electron scanning micrograph.Wherein Fig. 2 (A) is a tangent plane, and Fig. 2 (B) is the surface.
The specific embodiment
The embodiment that the invention is further illustrated by the following examples, but be not limited to these embodiment.
Embodiment 1 at first makes people's ear model with Gypsum Fibrosum, puts into the copper diaphragm capsule, and level up the bottom; Silicone rubber host and firming agent are restrained with 10: the mixed of 0.68 gram is even, inserts diaphragm capsule then, and compacting was at room temperature solidified 5 minutes, and the demoulding obtains flexible die A (former A); A puts into diaphragm capsule with former, puts into people's ear model again, repeats said process and obtains former B; Simultaneously, design and processing copper rigid die make flexible die just can put into rigid die; With 0.3 gram viscosity-average molecular weight is that 55000 PCL is dissolved in the chloroformic solution that forms PCL in the 6 gram chloroforms, sodium chloride porogen particle is sieved, get 2.7 gram particles and directly add in the solution (sodium chloride consumption account for macromolecule PCL and sodium chloride gross weight 90%) for 280-450 μ m sodium chloride particle, stir, cast on the glass plate, treat that the solvent final vacuum drying of partly volatilizing removes residual solvent, obtain the macromolecule/porogen complex of mix homogeneously, it is cut into lamellar; A puts into rigid die with flexible die, inserts macromolecule/porogen complex, covers flexible die B, compress metal platen, put between rubber vulcanizing machine two block pressur plates and heat, material softens gradually and constantly is compacted, and keeps 5 minutes down with abundant typing at 80 ℃; The demoulding obtains having the solid support of the macromolecule/porogen complex of required form, puts into the beaker that fills deionized water after cutting off the corner flash, changed one time water in per 4 hours, detect with silver nitrate aqueous solution after 48 hours, white precipitate do not occur, show that the porogen particle leaches fully; Wet porous support is taken out gently, inhale with toilet paper and to go the most of moisture of adsorbing in the support, at room temperature dried in the air again 24 hours, removing residual moisture in room temperature, vacuum under＞755mmHg the condition then, finally obtain having the PCL porous support (see figure 1) of people's ear complex appearance, porosity 84.3%, the hole height links to each other, and the rack surface void density is near the rack body (see figure 2).
Embodiment 2 PCL consumptions 0.15 gram, chloroform consumption 6 grams, sodium chloride particle consumption 2.85 grams, other is with embodiment 1.Make the PCL porous support that porosity 92.9%, hole height link to each other, the rack surface void density is high with people's ear complex appearance.
Embodiment 3 used macromolecules are that viscosity-average molecular weight is 41000 PDLLA, consumption 0.45 gram, and chloroform consumption 6 grams, sodium chloride particle consumption 2.55 grams, hot pressing temperature is 120 ℃.Other is with embodiment 1.Make the PDLLA porous support that porosity 78.9%, hole height link to each other, the rack surface void density is high with people's ear complex appearance.
Embodiment 4 PDLLA consumptions 0.30 gram, chloroform consumption 6 grams, sodium chloride particle consumption 2.70 grams.Other is with embodiment 3.Make the PDLLA porous support that porosity 89.0%, hole height link to each other, the rack surface void density is high with people's ear complex appearance.
Claims (17)
1, a kind of used in tissue engineering high-molecule porous scaffold is characterized in that having and human or animal's defective tissue or the similar complex appearance of organ; Its size and real human or animal's defective tissue or organ or its a part of size are suitable, or scaled or amplification; Its porosity ranges is 50%-99%, and the pore structure that is interconnected, its hole dimension are arranged is 10-900 μ m; Rack surface is a loose structure, and the rack surface void density approaches internal stent.
2, high-molecule porous scaffold according to claim 1 is characterized in that being of a size of 1/5～1/2 of true human or animal's tissue or organ size.
3, high-molecule porous scaffold according to claim 1 is characterized in that aperture size is 90～450 μ m.
4, high-molecule porous scaffold according to claim 1, the macromolecular material that it is characterized in that constituting support is to have good biocompatibility and biodegradable, any in polyhydroxycarboxyliacid acid ester, poe, poly-anhydride or copolymer of being made up of them or the blend, molecular weight is 10,000-3,000,000.
5, a kind of preparation method of high-molecule porous scaffold as claimed in claim 1 is characterized in that concrete preparation process is as follows:
(1) at first modeling material is made into the shape of required tissue or organ, is organized or the model of organ;
(2) above-mentioned tissue or organ model are put into diaphragm capsule, insert diaphragm capsule after flexible die material and firming agent thereof are mixed, compacting is at room temperature solidified, and the demoulding obtains flexible die former A; A puts into diaphragm capsule with former, puts into above-mentioned tissue or organ model again, repeats said process and obtains former B; Simultaneously, design and processing metal rigid die make flexible die just can put into rigid die;
(3) Biodegradable high molecular is dissolved in solvent orange 2 A, form macromolecular solution, then the porogen particle is added in the solution, stir, gained paste-like macromolecule/solvent/porogen complex is cast on glass plate or the polyfluortetraethylene plate, make most of solvent evaporates under the room temperature, vacuum drying removes residual solvent, with the gained macromolecule/the porogen complexes membrane is cut into lamellar or strip is standby;
(4) flexible die A is put into rigid die, insert macromolecule/porogen complex, cover flexible die B, compress metal platen, put between two block pressur plates of hot-press equipment, heat up, material softens gradually and constantly is compacted, and keeps certain hour with abundant typing, treats the suitably cooling back demoulding;
(5) obtain having the solid support of the macromolecule/porogen complex of required form after the demoulding, it leached the porogen particle with solvent B, treat that the porogen particle leaches fully after, the porous support that obtains wetting;
(6) wet porous support is taken out from solvent B, remove solvent B, obtain the used in tissue engineering degradable macromolecule porous support with defective tissue or the same complex appearance of organ of having that the rack surface void density approaches internal stent.
6, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that making tissue or material that organ model adopted and is a kind of of Gypsum Fibrosum, wax, timber, rigid plastics.
7, the preparation method of high-molecule porous scaffold according to claim 5, the material that it is characterized in that making flexible die is the macromolecular elastomer material, comprises silastic material, thiorubber. material, polyether rubber material etc.
8, the preparation method of high-molecule porous scaffold according to claim 5, it is characterized in that used diaphragm capsule made by metal material or plastics, wherein metal material is carbon steel, rustless steel, copper, aluminum or its alloy, and plastics are thermosetting plasticses such as thermoplastics such as polyvinyl chloride, politef, polypropylene, polymethyl methacrylate, Merlon and phenolic resins.
9, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that used rigid die made by metal material carbon steel, rustless steel, copper, aluminum or its alloy.
10, the preparation method of high-molecule porous scaffold according to claim 5, it is characterized in that flexible die can be enclosed within integral body of formation in the rigid die, rigid die provides the ability of bearing pressure, and flexible die provides the ability that accurately forms contoured cradle and improve the support release property.
11, the preparation method of high-molecule porous scaffold according to claim 5, it is characterized in that solvent orange 2 A is the solubilized macromolecule but does not dissolve the solvent of porogen, is specially any or its mixture in chloroform, dichloromethane, oxolane, the acetone.
12, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that solvent B is the solubilized porogen but does not dissolve used high molecular solvent, is specially tap water, pure water, deionized water.
13, the preparation method of high-molecule porous scaffold according to claim 5, it is characterized in that used porogen particle is dissolved in solvent B but is insoluble to solvent orange 2 A, is specially any or its mixture in sodium chloride, sodium citrate, sodium tartrate, sucrose, polyacrylic acid, the sodium polyacrylate.
14, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that used porogen particle size range is 10-900 μ m, and the porogen amount ranges is 50wt%-99wt%.
15, the preparation method of high-molecule porous scaffold according to claim 5, it is characterized in that processing object does not contain solvent when hot-forming, dependence is warming up to the above processability that obtains of macromolecule vitrification point or fusing point, in mould by the required contoured cradle of hot-forming acquisition; This complex support that the demoulding obtains has good shape hold facility.
16, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that hot-press equipment is adopted as rubber vulcanizing machine or other hot-press equipment.
17, the preparation method of high-molecule porous scaffold according to claim 5 is characterized in that forming temperature is higher than high molecular fusing point or vitrification point 5-100 ℃, and the dwell time is 1-30 minute.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109152862A (en) * | 2016-02-17 | 2019-01-04 | 多伦多大学管理委员会 | Biodegradation type bulking of soft tissue |
| CN113331990A (en) * | 2021-04-22 | 2021-09-03 | 中国人民解放军空军军医大学 | Drug-loaded elastic degradable artificial blood vessel and construction method thereof |
| CN113368307A (en) * | 2021-01-04 | 2021-09-10 | 山东百多安医疗器械股份有限公司 | Ear support construction material and preparation process thereof |
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2002
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109152862A (en) * | 2016-02-17 | 2019-01-04 | 多伦多大学管理委员会 | Biodegradation type bulking of soft tissue |
| CN113368307A (en) * | 2021-01-04 | 2021-09-10 | 山东百多安医疗器械股份有限公司 | Ear support construction material and preparation process thereof |
| CN113368307B (en) * | 2021-01-04 | 2023-02-10 | 山东百多安医疗器械股份有限公司 | Ear support construction material and preparation process thereof |
| CN113331990A (en) * | 2021-04-22 | 2021-09-03 | 中国人民解放军空军军医大学 | Drug-loaded elastic degradable artificial blood vessel and construction method thereof |
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