CN1341458A - Low-temp. extrusion/jet-stacking forming process of structure engineering carrier frame - Google Patents
Low-temp. extrusion/jet-stacking forming process of structure engineering carrier frame Download PDFInfo
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- CN1341458A CN1341458A CN 01141863 CN01141863A CN1341458A CN 1341458 A CN1341458 A CN 1341458A CN 01141863 CN01141863 CN 01141863 CN 01141863 A CN01141863 A CN 01141863A CN 1341458 A CN1341458 A CN 1341458A
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Abstract
The production process of human body tissue engineering carrier frame includes the following steps: firstly, preparing liquor containing tissue engineering carrier frame material and liquid containing growth factor at room temp., according to the user's requirements and previously designed and defined pathway extruding or jetting the above-mentioned two liquors respectively by means of different sprayers in the low-temp. environment of below zero deg.C, and making them form layer-by-layer stacked frozen porous tissue engineering carrier frame, then freeze-dried in freeze-drying machine, removing solvent so as to obtain the invented tissue engineering carrier frame. Its formation process and porosity structure of the frame, and the pore size and its through property can be well controlled, so that it is favorable for internal degradation of carrier frame in human body and nutrition and metabolism of regenerated tissue, and can well retain the bio-activity of biological material.
Description
Technical field
The invention belongs to product shaping Technology field, particularly a kind of human tissue engineering carrier frame is made forming technique and method.
Background technology
The manufacturing process of the carrier frame of organizational project generally adopts foaming, solution technique, cement-dipping method and thermally induced phase separation etc. in the world at present.These technologies are all followed similar principle, and that is exactly by indirect means pore-creating, and as adding foaming agent, sugar, inorganic salt, mandruka and organic solvent etc. as pore creating material, the morphological parameters of hole and the selection of pore creating material have direct relation.
For example the typical process of cement-dipping method---the polyurethane sponge cement-dipping method immerses polyurethane sponge in the ceramic size exactly, then 125 ℃ of dryings 1 hour, speed with 0.5 ℃/min is heated to 500 ℃, be heated to high temperature with the speed of 1 ℃/min again and burn till, the principle of its process as shown in Figure 1.This process agglomerating ceramic monolith framework that can only be shaped, and many biomaterials can not bear the pyritous course of processing, therefore available material is restricted.
There is following problem usually in these traditional engineering carrier frame manufacturing process:
(1). 200 μ m-500 μ m size ranges and the mutual control pore structure that connects are difficult to be shaped.Because these technologies all are indirect pore-creating (by foaming agent, inorganic salts or the like), be difficult to realize directly effectively controlling for the carrier frame pore structure, there is randomness to a certain extent in the pore structure that is shaped, is difficult to satisfy the morphological parameters requirement of engineering carrier frame---200 μ m-500 μ m size ranges and the control pore structure that connects mutually;
(2). be difficult to realize the shaping of porosity gradient structure and material gradient-structure.The carrier frame that this even pore structure and material are formed is difficult to coordinate contradiction between the degradation property of carrier frame and the mechanical strength, is difficult to satisfy the complicated performance requirement of engineering carrier frame;
(3). be difficult to realize customized carrier frame manufacturing.Because the tissue defect situation of different cases varies, need at concrete case design and manufacturing carrier frame, traditional process is difficult to realize.
Summary of the invention
The objective of the invention is to overcome the weak point of traditional engineering carrier frame forming technology, low temperature extruding/jet-stacking the forming technology that provides a kind of engineering carrier frame to make, make it easy to reach the morphological parameters requirement and the complicated performance requirement of engineering carrier frame, realize the shaping of porosity gradient structure and material gradient-structure, realize customized carrier frame manufacturing.
The present invention proposes the low temperature extruding/jet-stacking forming process of structure that a kind of engineering carrier frame is made, and carries out as follows successively:
A kind of low temperature extruding/jet-stacking moulding technique of engineering carrier frame, its technology is carried out successively as follows:
A. with required engineering carrier frame material and solvent, be prepared into and contain organizational project under the room temperature and carry
The liquid of body frame material; And the preparation room relaxing the bowels with purgatives of warm nature contains the liquid of required somatomedin;
B. according to the concrete structure of user group and in advance the design the path, with the above-mentioned engineering carrier frame that contains
The liquid of frame material and the liquid that contains somatomedin in being lower than 0 ℃ low temperature environment respectively by different
Shower nozzle extrude or eject, successively stack shaping is refrigerated multi-porous tissue engineering carrier frame;
C. above-mentioned refrigerated engineering carrier frame is sent into lyophilization in the freeze dryer, get final product behind the removal solvent
Obtain engineering carrier frame.
In the above-mentioned steps of the present invention, the liquid that the preparation described in a step contains the engineering carrier frame material is the partly soluble slurry of solution, suspension, emulsion or material that contains the engineering carrier frame material; The liquid that contains required somatomedin under the described room temperature is the partly soluble slurry of solution, suspension, emulsion, somatomedin that comprises somatomedin.
The principle of process of the present invention and characteristics:
1) principle of low temperature extruding/jet-stacking forming process of structure is based on discrete/accumulation ultimate principle that quick shaping is made, the pore structure of forming process and framework can carry out stack shaping successively according to design in advance, therefore, pore-size and mutual connectivity can be well controlled.
2) because in the present invention, the preparation of material is at room temperature to adopt the mode of dissolution with solvents or liquid suspension to obtain liquid moulding material, and do not adopt the liquid material preparation method of any heating and melting, therefore well kept the biological activity of biomaterial, made this technology have material adaptability widely.
3) this process using freeze-drying method is with the removal of solvents in the engineering carrier frame of freezing state, the distillation of solvent has stayed the microcellular structure of the mutual perforation of the following size of a large amount of 50 μ m in this operation, improve the porosity of carrier frame, helped the nutrition and the metabolism of the vivo degradation and the regenerating tissues of carrier frame.
4) because the huge flexibility of the fast shaping technology that the present invention adopts aspect the manufacturing complicated shape can realize customized carrier frame manufacturing.
Description of drawings
Fig. 1 is the polyurethane sponge cement-dipping method process schematic representation of available technology adopting;
Fig. 2 is low temperature extruding/jet-stacking forming process of structure sketch map;
Fig. 3 is low temperature extruding/jet-stacking former structural representation;
Fig. 4 is for utilizing the bone tissue engineer carrier frame with process manufacturing of the present invention;
Fig. 5 is the pore structure photo of the bone tissue engineer carrier frame of scanning electron microscopic observation manufacturing.
The specific embodiment
The principle of the low-temp. extrusion/jet-stacking forming process of structure of engineering carrier frame as shown in Figure 2, At first engineering carrier frame material and solvent are prepared into and contain the engineering carrier frame material under the room temperature The liquid of material prepares the liquid that contains growth factor under the room temperature. Different tissues need adopt different organizational projects to carry The body frame material, as: bone tissue engineer often adopts degradable high polymer material, calcium microcosmic salt or their composite wood Material, intravascular tissue engineering often adopts polyurethane material etc. Different materials need be dissolved in different solvents, has Material is insoluble to solvent, and insoluble part is prepared into the following powder of 10 μ m. Contain under the preparation room temperature and organize the worker The liquid of journey carrier frame material comprises solution, suspension, the emulsion of engineering carrier frame material or is somebody's turn to do The partly soluble slurry of material. Equally, different tissues needs different growth factors, and different growth factors needs Be dissolved in different solvents, the growth factor that has is insoluble to solvent, and insoluble part is prepared into below the 10 μ m Powder. The liquid that contains growth factor under the preparation room temperature comprises solution, suspension, emulsion, the life of growth factor The long partly soluble slurry of the factor or growth factor evenly are blended in the aforementioned engineering carrier frame material that contains Mixture in the liquid. According to the path of in advance design code, will contain by different shower nozzles respectively then Engineering carrier frame material liquid and the liquid that contains growth factor in being lower than 0 ℃ low temperature environment, squeeze Go out or eject, successively pile up and the multi-porous tissue engineering carrier frame of freezing shaping. Adopt this process Equipment principle as shown in Figure 3. According to the path of in advance design code, jet head sets 3 will be housed in storage tank The liquid material of group in 2, the mode by extruding or spraying respectively, in being lower than 0 ℃ cryogenic forming chamber 5, Successively be deposited on the workbench 1, obtain freezing engineering carrier frame 4. The pore structure of framework can By design in advance, can obtain by the scanning motion track that computer or other modes are controlled shower nozzle, Pore-size and mutual connectivity can be well controlled. Each shower nozzle in the jet head sets all can be under control Do independently scanning motion, extrude/spray different materials, according to design shaping material gradient structure in advance. With the freeze drying in freeze dryer of freezing carrier frame, obtain the worker that organizes for tissue repair behind the removal of solvents The journey carrier frame.
Embodiment:
The bone tissue engineer carrier of embodiments of the invention for making by low-temp. extrusion/jet-stacking forming technology Framework, as shown in Figure 4. The engineering material of bone tissue that adopts is biodegradable high molecular polymer and calcium The mixture of microcosmic salt, the growth factor of employing are bone morphogenetic protein. At first with engineering material of bone tissue and chlorine Imitate being mixed with into liquid slurry, prepare simultaneously the aqueous suspension of bone morphogenetic protein, then with these two kinds Liquid raw material is respectively charged in two storage tanks, respectively to the shower nozzle transferring raw material of two special uses. Shower nozzle is at meter Under the control of calculation machine bi-material is extruded/sprayed in being lower than 0 ℃ cryogenic forming chamber, and successively be piled into Shape obtains freezing bone tissue engineer carrier frame, through after the freeze drying process, obtains shown in Figure 4 Tissue carrier's frame structure. Under the control of computer, the carrier frame of shaping possesses 200 μ m-500 μ m Size range and the control pore structure that mutually connects have realized the one-tenth of porosity gradient structure and material gradient-structure Shape. By the patient CT pictorial data behind the employing three-dimensionalreconstruction, can realize that customized carrier frame is shaped. Fig. 5 is the pore structure photo of the bone tissue engineer carrier frame of scanning electron microscopic observation embodiment manufacturing, this figure The macroporous structure that can see 400 μ m after the amplification has been covered with the following small structure that mutually connects of 50 μ m.
Claims (2)
1. the low temperature extruding/jet-stacking forming process of structure of an engineering carrier frame, its feature is carried out successively as follows:
A. with required engineering carrier frame material and solvent, be prepared into and contain organizational project under the room temperature and carry
The liquid of body frame material; And the preparation room relaxing the bowels with purgatives of warm nature contains the liquid of required somatomedin;
B. according to the concrete structure of user group and in advance the design the path, with the above-mentioned engineering carrier material that contains
Liquid and the liquid that contains somatomedin of material in being lower than 0 ℃ low temperature environment respectively by different sprays
Head is extruded or is ejected, and successively stack shaping is refrigerated multi-porous tissue engineering carrier frame;
C. above-mentioned refrigerated engineering carrier frame is sent into lyophilization in the freeze dryer, get final product behind the removal solvent
Obtain engineering carrier frame.
2. according to the low temperature extruding/jet-stacking forming process of structure of the described a kind of engineering carrier frame of claim 1, it is characterized in that the liquid that contains the engineering carrier frame material described in the above-mentioned a step is the partly soluble slurry of solution, suspension, emulsion or material that contains the engineering carrier frame material, the liquid that contains required somatomedin under the described room temperature is the partly soluble slurry of solution, suspension, emulsion, somatomedin that comprises somatomedin.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01141863 CN1341458A (en) | 2001-09-21 | 2001-09-21 | Low-temp. extrusion/jet-stacking forming process of structure engineering carrier frame |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01141863 CN1341458A (en) | 2001-09-21 | 2001-09-21 | Low-temp. extrusion/jet-stacking forming process of structure engineering carrier frame |
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| CN1341458A true CN1341458A (en) | 2002-03-27 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100404080C (en) * | 2006-03-24 | 2008-07-23 | 清华大学 | Water gel fast forming process based on bionic process |
| CN101219240B (en) * | 2008-01-18 | 2010-11-10 | 清华大学 | Production method for living body tissue with channel |
| CN102600504A (en) * | 2012-03-20 | 2012-07-25 | 杭州电子科技大学 | Preparation method of mulberry silk tissue engineering scaffold |
| CN103587119A (en) * | 2013-11-13 | 2014-02-19 | 清华大学深圳研究生院 | Three-dimensional biological material forming equipment and extrusion nozzles thereof |
| TWI577448B (en) * | 2016-01-04 | 2017-04-11 | 國立中央大學 | Manufacturing method of low-temperature rapid manufacturing support structure and manufacturing method of low-temperature rapid manufacturing support structure |
| CN107041971A (en) * | 2016-09-19 | 2017-08-15 | 盐城工业职业技术学院 | A kind of fibroin based on 3 D-printing/gelatin timbering material and preparation method thereof |
-
2001
- 2001-09-21 CN CN 01141863 patent/CN1341458A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100404080C (en) * | 2006-03-24 | 2008-07-23 | 清华大学 | Water gel fast forming process based on bionic process |
| CN101219240B (en) * | 2008-01-18 | 2010-11-10 | 清华大学 | Production method for living body tissue with channel |
| CN102600504A (en) * | 2012-03-20 | 2012-07-25 | 杭州电子科技大学 | Preparation method of mulberry silk tissue engineering scaffold |
| CN102600504B (en) * | 2012-03-20 | 2014-07-09 | 杭州电子科技大学 | Preparation method of mulberry silk tissue engineering scaffold |
| CN103587119A (en) * | 2013-11-13 | 2014-02-19 | 清华大学深圳研究生院 | Three-dimensional biological material forming equipment and extrusion nozzles thereof |
| CN103587119B (en) * | 2013-11-13 | 2015-11-18 | 清华大学深圳研究生院 | Biomaterial three-dimensional equipment and extrude shower nozzle |
| TWI577448B (en) * | 2016-01-04 | 2017-04-11 | 國立中央大學 | Manufacturing method of low-temperature rapid manufacturing support structure and manufacturing method of low-temperature rapid manufacturing support structure |
| CN107041971A (en) * | 2016-09-19 | 2017-08-15 | 盐城工业职业技术学院 | A kind of fibroin based on 3 D-printing/gelatin timbering material and preparation method thereof |
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