CN101147812A - Three-dimension porous tissue engineering carrier material and preparation and application - Google Patents
Three-dimension porous tissue engineering carrier material and preparation and application Download PDFInfo
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- CN101147812A CN101147812A CNA2007100475528A CN200710047552A CN101147812A CN 101147812 A CN101147812 A CN 101147812A CN A2007100475528 A CNA2007100475528 A CN A2007100475528A CN 200710047552 A CN200710047552 A CN 200710047552A CN 101147812 A CN101147812 A CN 101147812A
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Abstract
The present invention relates to a three-dimensional porous tissue engineering carrier material, its preparation and application. Said three-dimensional porous tissue engineering carrier material includes three-dimensional porous structure, its internal porous structure is uniform, three-dimensional through degree is above 90%, pore size is 50-500 micrometer and porosity is 65-90%. Its preparation method includes the following steps: using polyhydroxybutyrate valerate (PHBV) and polycaprolactone (PCL) as raw material, mixing them, melting and spinning to obtain fibre whose diameter is 10-500 micrometer, cutting said fibre to make said fibres have identical length, making said fibres be uniformly arranged and filled into a mould, sealing said mould for 5min-1n at 50-80deg.C, demoulding, sterilizing and packaging so as to obtain the invented product. Said product can be used for repairing or reconstructing some tissue organs.
Description
Technical field
The invention belongs to bioengineered tissue carrier material and preparation and application, particularly relate to a kind of three-dimension porous tissue engineering carrier material and preparation and application.
Background technology
The tissue and the forfeiture of organ or dysfunction are one of main harm of facing of human health, also are one of main reasons of human diseases and death.Though and traditional autotransplantation, heteroplastic transplantation and artificial succedaneum have shown excellent curative, the immunologic rejection of its existence, donor source is limited or their application that needed drawbacks limit such as second operation.In recent years, an ideal strategy is exactly artificial culture tissue and organ, the notion of " organizational project " has been proposed immediately, its basic skills is exactly Langer R, Vacanti J P.Tissue Engineering.Science, 1993,260 (5110): propose in 920: it is good and can progressively on the biomaterial of degraded and absorbed, be formed cell " biological composite " by human body in a kind of biocompatibility that the high concentration histiocyte absorption of In vitro culture is increased; The disease of this cell " biomaterial composites " being implanted when injected organism tissue is decreased the position then, and the cell of plantation continues propagation justacrine substrate in the process that the bio-carrier material is progressively degraded, and forms new having and self function and corresponding tissue of form and organ.Thereby this Biodegradable material provides the support of growth of new tissue as the carrier of cell, is the key of artificial culture tissue and organ.
At present, the biomaterial that is applied to engineering carrier is existing a variety of, mainly comprise natural macromolecular material, as chitin, collagen etc. and synthesized polymer material, as PLA, PGA, PGLA and PHB etc., but there is different separately defectives mostly in these materials, are difficult to satisfy the high request of clinical practice.For example, natural polymer lacks necessary space structure and mechanical strength usually; PLA and PGA class material then ubiquity degradation speed cause problems such as aseptic inflammation reaction too soon.The method for preparing carrier material also has a variety of at present, comprises fiber bonding method, solvent cast---particle leaching method, gas pore method, chemical blowing process, sintering microsphere method, lyophilization and 3 D-printing technology etc.
Because the research of organizational project still belongs to the starting stage, the document and the patent report of preparation aspect that is relevant to tissue carrier material both at home and abroad is also few.Along with organizational project in recent years becomes the research focus gradually, the successful report in existing many animal experiment stages is seen in document.Some researcheres are applied to polycaprolactone in the preparation of tissue carrier material, but the preparation method that adopts is had nothing in common with each other, for example: it is material that people such as G.Torun Kose adopt PHBV, in conjunction with solvent cast/particle leaching method, making the aperture is 75-300 μ m or 300-500 μ m three-dimension porous tissue engineering carrier material; Human sucrose such as S.-J.Shieh prepare shape template, then in conjunction with solvent cast/particle leaching method, make the cartilage tissue engineered carrier material of ear shape PCL and PHB material, and have studied it in the intravital biological nature of nude mice; Human electrostatic spinnings such as Wan-Ju Li prepare the PCL nanofiber, adopt the PCL nanofiber to prepare nanofiber porous support (NFS) then; The patent " tissue engineered porous scaffold preparation method " of people such as domestic Ren Jie application, application number 200410025456.X, propose the copolymer of poly lactic acid granule is placed in the mould hot-forming among the publication number CN1711977A, the copolymer of poly lactic acid with molding under the room temperature is put into high pressure CO
2Machinery is saturated in the gas, adopts gas expansion method to prepare porous support; The patent " a kind of three-dimensional porous tissue engineering bracket material and preparation method thereof " of people such as Ren Lei application, application number 200410094895.6 proposes among the publication number CN1613514A to prepare bone and cartilage tissue engineered rack material by collagen/chitosan/GPSM/ lime nitrate intermingling material by freeze-drying.Obviously, adopting PHBV/PCL at present is biomaterial, and the method for preparing tissue carrier material by the fiber sintering method does not have similar or similar patent or bibliographical information both at home and abroad.
The present invention adopts the high polymer blend melt spinning to combine the preparation tissue carrier material with the fiber sintering method, the fibers melt mull technique is to utilize low these characteristics of polycaprolactone fusing point in poly butyric valerate/polycaprolactone (PHBV/PCL) blend, at first fiber is positioned over and piles up molding in the particular model, the reuse vacuum drying oven is accurately controlled heating-up temperature, makes fiber overlapping place bonding form three-dimensional porous structure.So not only make the carrier material one-shot forming, and can obtain higher porosity.Because PHBV and PCL possess the degradation speed of excellent biological compatibility, controllable adjustment, thereby the clinical needs of multiple organizational projects such as applicable bone, cartilage.The present invention has avoided adopting in present all multi-methods the shortcoming of organic solvent in preparation process, have simple equipments than some rapid shaping techniques simultaneously, and technology is the characteristics of control easily.Key problem in technology of the present invention is determining of two kinds of high polymer co-blended spinning technologies, and the fibrous material of certain diameter and length and specific heating-up temperature and corresponding relation of time is definite.
Summary of the invention
The objective of the invention is to deficiency, develop a kind of tissue carrier material that good biocompatibility, degradation rate and tissue regeneration are complementary that possesses, to adapt to the demand of Different Organs tissue repair at existing biomaterial and preparation method.
A kind of three-dimension porous tissue engineering carrier material of the present invention is three-dimensional porous structure, and even, the three-dimensional perforation degree of internal pore structure is more than 90%, and the aperture is at 50～500 μ m, and porosity is 65～90% variations.The preparation raw material can adopt two kinds of biodegradable polymer---poly butyric valerate (PHBV), polycaprolactone (PCL).
The preparation method of a kind of three-dimension porous tissue engineering carrier material of the present invention may further comprise the steps:
1) raw material poly butyric ester valerate (PHBV)/polycaprolactone (PCL) blend melt spinning is made the fiber that diameter is 10～500 μ m, the molecular weight ranges of described PHBV is 10～750,000, spinning temperature is 175～220 ℃, the molecular weight ranges of PCL is 1～200,000, and fusing point is 55～65 ℃;
2) the PHBV/PCL blended fiber is cut into equal length, evenly distributed being filled in the mould, described fiber length ranges is 1～10mm;
3) behind the die sealing with populated fiber, place vacuum drying oven constant temperature to keep 5min～1h, described vacuum drying oven temperature is 50～80 ℃;
4) from vacuum drying oven, take out mould, the room temperature cooling back demoulding;
5) will be ready for use on organizational project after three-dimensional porous carrier material sterilization, the packing, its profile can be certain organs shapes such as ear, nose.
A kind of three-dimension porous tissue engineering carrier material of the present invention is specially adapted to bone or cartilage tissue engineered organ reparation and reconstruction.
Fibre diameter of the present invention is 10～500 μ m, regulates the diameter of fiber, and the pore size that can control porous carrier materials is 50～500 μ m, meets the demand of cell growth and tissue regeneration.Length is 1～10mm after the fiber cutting, it is characterized in that guaranteeing having good three-dimensional through hole structure after the fiber clinkering, and the perforation degree is more than 90%.Mould constant temperature clinkering 5 minutes～1 hour in 50～80 ℃ of environment is kept certain hour and is made the inside and outside conduction of heat of mould even, and fiber is even bonding one-tenth net in the cross point, forms three-dimensional porous structure.
Description of drawings
Fig. 1 is the electron microscopic mirror image of PHBV/PCL three-dimension porous tissue engineering carrier material.
The specific embodiment
The invention will be further elaborated below by specific embodiment, but embodiment only is used for explanation, does not limit scope of invention.
Embodiment 1
With molecular weight is 100,000, fusing point is 60 ℃ high polymer PCL, and molecular weight is 460,000, fusing point is 174 ℃ high polymer PHBV, melt spinning gets the fiber that average diameter is 500 μ m under 175 ℃ of conditions, after being cut to isometric 10.0mm, be filled in the given shape mould, filling quality is 85% calculating with porosity, the vacuum drying oven temperature is set at 75 ℃, die sealing is placed on that constant temperature took out after 1 hour in the vacuum drying oven, the room temperature cooling back demoulding, the tissue carrier material that just obtains having given configuration and superperformance.It is 50-200 μ m that material records the aperture through scanning electron microscope, and recording porosity by liquid displacement technique is 82%, and hole perforation degree reaches more than 90%, and the external degradation cycle is suitable, good mechanical performance.This material is applicable to the bone tissue engineer carrier material, as the repair and reconstruction of bone injury.
Embodiment 2
With molecular weight is 80,000, fusing point is 58～60 ℃ high polymer PCL, and molecular weight is 460,000, fusing point is that high polymer PHBV melt spinning under 175 ℃ of conditions of 174 ℃ gets the fiber that average diameter is 500 μ m, after being cut to isometric 10.0mm, be filled in the given shape mould, filling quality is 85% calculating with porosity, the vacuum drying oven temperature is set at 75 ℃, die sealing is placed on that constant temperature took out after 1 hour in the vacuum drying oven, the room temperature cooling back demoulding, the tissue carrier material that just obtains having given configuration and superperformance.It is 50-200 μ m that material records the aperture through scanning electron microscope, and recording porosity by liquid displacement technique is 84%, and hole perforation degree reaches more than 90%, and the external degradation cycle is suitable, good mechanical performance.This material is applicable to the bone tissue engineer carrier material, as the repair and reconstruction of bone injury.
Embodiment 3
With molecular weight is 50,000, fusing point is 58～60 ℃ high polymer PCL, and molecular weight is 460,000, fusing point is that high polymer PHBV melt spinning under 175 ℃ of conditions of 174 ℃ gets the fiber that average diameter is 500 μ m, after being cut to isometric 6.0mm, be filled in the given shape mould, filling quality is 85% calculating with porosity, the vacuum drying oven temperature is set at 75.0 ℃, die sealing is placed on that constant temperature took out after 1 hour in the vacuum drying oven, the room temperature cooling back demoulding, the tissue carrier material that just obtains having given configuration and superperformance.It is 300～500 μ m that material records the aperture through scanning electron microscope, and recording porosity by liquid displacement technique is 75%, and the external degradation cycle is suitable, good mechanical performance.This material is applicable to the bone tissue engineer carrier material, as the repair and reconstruction of bone injury.
Claims (7)
1. a three-dimension porous tissue engineering carrier material is characterized in that, three-dimensional porous structure, and even, the three-dimensional perforation degree of internal pore structure is more than 90%, and the aperture is at 50～500 μ m, and porosity is 65～90% variations.
2. a kind of three-dimension porous tissue engineering carrier material according to claim 1 is characterized in that: raw material polycaprolactone molecular weight (M
w) be 1～200,000, fusing point is 55～65 ℃; Raw material poly butyric ester valerate: molecular weight (M
w) be 10～750,000, fusing point is 150～180 ℃.
3. the preparation method of a three-dimension porous tissue engineering carrier material may further comprise the steps:
1) poly butyric ester valerate (PHBV)/polycaprolactone (PCL) blend melt spinning is made the fiber that diameter is 10～500 μ m,, spinning temperature is 175～220 ℃;
2) be 10～500 μ m with PHBV/PCL blended fiber diameter, be cut into 1～10mm equal length, evenly distributed being filled in the mould;
3) behind the die sealing with populated fiber, place vacuum drying oven constant temperature to keep 5min～1h, oven temperature is 50～80 ℃;
4) from vacuum drying oven, take out mould, the room temperature cooling back demoulding;
5) with three-dimensional porous carrier material sterilization, packing.
4. the preparation method of a kind of three-dimension porous tissue engineering carrier material as claimed in claim 3, it is characterized in that: the spinning temperature of melt spinning method is 175～220 ℃, blend time 3～5min, spinning process is not used any organic solvent.
5. the preparation method of a kind of three-dimension porous tissue engineering carrier material as claimed in claim 3 is characterized in that: fiberfill fibers in the mould, it is characterized in that filling quality is 60～95% to calculate with porosity, and fiber alignment becomes homogeneous texture.
6. a three-dimension porous tissue engineering carrier material is applied to organizational project.
7. the application of a kind of three-dimension porous tissue engineering carrier material as claimed in claim 6 is characterized in that: be used for bone or cartilage tissue engineered organ reparation and reconstruction, its profile is certain organs shapes such as ear, nose.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104674454A (en) * | 2015-01-27 | 2015-06-03 | 浙江大学 | Method for manufacturing three-dimensional porous disorder scaffolds from polylactic acid molten spinning fibers by means of thermal bonding and solidifying |
| CN113198051A (en) * | 2021-04-28 | 2021-08-03 | 四川轻化工大学 | Preparation method of three-dimensional composite porous scaffold and three-dimensional composite porous scaffold |
-
2007
- 2007-10-30 CN CNA2007100475528A patent/CN101147812A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104674454A (en) * | 2015-01-27 | 2015-06-03 | 浙江大学 | Method for manufacturing three-dimensional porous disorder scaffolds from polylactic acid molten spinning fibers by means of thermal bonding and solidifying |
| CN106757772A (en) * | 2015-01-27 | 2017-05-31 | 浙江大学 | The preparation method that fiber heat bonding solidifies three-dimensional porous unordered support is spun in a kind of PLA melting |
| CN113198051A (en) * | 2021-04-28 | 2021-08-03 | 四川轻化工大学 | Preparation method of three-dimensional composite porous scaffold and three-dimensional composite porous scaffold |
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