CN101342099A - bioartificial liver cell reactor - Google Patents
bioartificial liver cell reactor Download PDFInfo
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- CN101342099A CN101342099A CNA2008101242604A CN200810124260A CN101342099A CN 101342099 A CN101342099 A CN 101342099A CN A2008101242604 A CNA2008101242604 A CN A2008101242604A CN 200810124260 A CN200810124260 A CN 200810124260A CN 101342099 A CN101342099 A CN 101342099A
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Abstract
本发明涉及一种新型生物人工肝细胞反应器。本发明技术特征是盖子在外壳上端，培养液出口在外壳下端，二层及二层以上平板重心对称设置，每层平板中间设置圆孔，表面设有二个以上小孔，并在平板表面纺有一层壳聚糖纳米纤维支架，平板通过中心圆孔固定在中空支架上，中空支架侧面设置侧孔。本发明解决了现有技术中空纤维型、单层平板型、灌注床型和包被悬浮型生物人工肝细胞反应器存在的各自缺陷。本发明增加反应器的有效交换面积，肝脏细胞贴壁培养且使细胞均匀分布，实现营养物质的充分交换，促进肝细胞在细胞支架表面的粘附，从而耐受培养液循环带来的剪切力。
The invention relates to a novel bioartificial liver cell reactor. The technical feature of the present invention is that the cover is at the upper end of the shell, the outlet of the culture solution is at the lower end of the shell, the center of gravity of the two-layer and above-two-layer plates is arranged symmetrically, a round hole is arranged in the middle of each plate, and more than two small holes are arranged on the surface, and the surface of the plate is spun. There is a layer of chitosan nanofiber support, the flat plate is fixed on the hollow support through a central hole, and side holes are arranged on the side of the hollow support. The invention solves the respective defects of the prior art hollow fiber type, single-layer plate type, perfusion bed type and coating suspension type bioartificial liver cell reactors. The invention increases the effective exchange area of the reactor, and the liver cells are adhered to the wall for cultivation and the cells are uniformly distributed, thereby realizing sufficient exchange of nutrients, promoting the adhesion of the liver cells on the surface of the cell scaffold, and thus enduring the shear caused by the circulation of the culture medium. force.
Description
Technical field
The present invention relates to a kind of medical apparatus and instruments, particularly a kind of novel biology artificial hepatocyte reactor.
Background technology
The bioartificial liver can be the patient of short duration liver function support is provided, and is effective auxiliary treatment means of diseases such as present liver failure, has a good application prospect.Bioreactor has determined wherein cell activity and function as bioartificial liver's nucleus, thereby has also determined bioartificial liver's performance.
Before the present invention, the bioreactor of present clinical use roughly is divided into four types: hollow fiber type, and the single flat template, perfusion bed type and bag are by floating type.Wherein hollow fiber bioreactor is that application is maximum at present, and it is that a branch of hollow fiber conduit is sealed in the shell of transparent organic material, and this fiber is divided into inside and outside two chambeies with shell, the mobile patient's blood plasma of general inner chamber, exocoel culture liver cell.This fiber also has the semipermeable membrane function simultaneously, realizes the two-way transportation of material in the time of isolated cell, thereby reaches the purpose that liver function is supported.
Yet this reactor remains in use in certain defective.At first, the fiber dense arrangement in this reactor is difficult for amplifying, and capacity and effective exchange area are little; Secondly, cell accumulation is incubated at the doughnut outside, often deposits the bottom easily, can not be uniformly distributed between the fiber; The 3rd, the cell dense accumulation is cultivated, and nutrition and oxygen exchange are limited, have also reduced cell activity when having limited function; At last, hepatocyte is an anchor foot like cell, and accumulated growth also can cause the decline of cytoactive.And in the perfusion bed system, though hepatocyte energy adhere-wall culture because it can not tolerate the shearing force that liquid circulation brings, often comes off easily.
Summary of the invention
Purpose of the present invention just is to overcome above-mentioned defective, designs, develops a kind of novel biology artificial hepatocyte reactor.
Technical scheme of the present invention is:
Novel biology artificial hepatocyte reactor, lid is in the shell upper end, the culture fluid outlet is in the shell lower end, its major technique is characterised in that two layers and two layers are symmetrical arranged with the upper flat plate center of gravity, in the middle of every layer of flat board circular hole is set, the surface is provided with two above apertures, and has spun one deck chitosan nano fiber support at planar surface, flat board is fixed on the hollow stent by center hole, and the hollow stent side is provided with side opening.
Advantage of the present invention and effect are that having solved the hollow fiber type reactor with multi-layer planar can not amplify, capacity and effective low problem of exchange area, and can make the even adhere-wall culture of cell simultaneously.Culture fluid has solved reactor and has stopped up easily from middle radial mobile to all around, and solution exchanges uneven problem.The quiet chitosan nano fiber that spins in multi-layer planar surface can promote hepatocyte to adhere to, and has solved the cell attachment instability, the problem that comes off easily.
Particularly:
(1) size of reactor can be amplified arbitrarily and dwindles by increasing and decreasing the dull and stereotyped number of plies; Multilamellar is circular dull and stereotyped stacked, in the effective exchange area that increases reactor, reduces reactor volume, can not amplify capacity and effective low shortcoming of exchange area thereby overcome the hollow fiber type reactor.
(2) cell is added by the opening on the hollow stent, and last adhere-wall culture had so both satisfied the requirement of liver cell need adhere-wall culture on each layer flat board, can make the cell uniform distribution again.
(3) be to be flowed out by the hollow stent side opening culture fluid circulation time, and then by radial outflow around the middle mind-set, culture fluid can be fully and cells contacting like this, when bringing cytotrophy, the useful component of emiocytosis is taken away, thus the abundant exchange of realization nutrient substance.
(4) cytoskeleton adopts chitosan nano fiber membrane, can well promote the adhesion of hepatocyte on its surface, thus the shearing force that the circulation of tolerance culture fluid brings.
Other advantage of the present invention and effect will go on to say below.
Description of drawings
Fig. 1---structural principle sketch map of the present invention.
Every layer of planar surface structural representation of Fig. 2---the present invention.
Fig. 3---the present invention uses sketch map.
The specific embodiment
As Fig. 1, Fig. 2, shown in Figure 3:
Whole liver cell reactor is made up of the multi-layer planar more than two layers and two layers 3, hollow stent 5 and shell 4; 50 layers flat board 3 is arranged in this example, and center of gravity is symmetrical arranged; On the surface of every layer of flat board 3 a plurality of apertures 8 are set, aperture 8 is equilateral arrangement, and diameter is adopted 1cm, spins last layer chitosan nano fiber support 10 simultaneously on its surface; Distance equates between per two layers of flat board 3, has the circular holes 9 of diameter 2cm in the middle of every layer of flat board 3, so that hollow stent 5 passes is fixing; Hollow stent 5 upper end open, lower end closed, its side is provided with several side openings 7, and is corresponding one by one with dull and stereotyped 3 numbers, 50 side openings 7 promptly are set in this example, and each side opening 7 all is positioned at every layer of flat board 3 surfaces; Flat board 3, hollow stent 5 all are arranged in the shell 4, and with lid 2 sealings, lid 2 is provided with culture fluid and cell inlet 1, culture fluid is set in the middle of shell 4 bottoms exports 6 above;
During application:
At first culture fluid outlet 6 is closed, to be mixed with hepatocellular culture fluid 11 is then added by culture fluid and cell inlet 1, culture fluid 11 is through hollow stent 5, because hollow stent 5 bottom locks, can only flow out to every layer of flat board 3 by the side opening 7 of hollow stent 5, final full whole reactor shell 4, cell is distributed in each layer flat board 3 surfaces equably in flow process; After application of sample finished, it is 1 airtight that culture fluid and cell are entered the mouth, and whole reactor is placed static half an hour under 37 ℃ of environment, makes the hepatocyte energy adherent in chitosan nano timbering material 10 surfaces.
After treating that cell attachment firmly, carry out the circulation of culture fluid.Culture fluid 11 is entered by culture fluid inlet 6, through hollow stent 5, flows out by side opening 7 again, and by radial flowing around the middle mind-set.When flowing through every layer of flat board 3 surfaces, culture fluid 11 can be hepatocyte nutrition and oxygen is provided, the excretory useful component of hepatocyte can be taken away again simultaneously, thus the abundant exchange of realization material.Flow out by culture fluid outlet 6 through the culture fluid 11 after the exchange.
The scope that the present invention asks for protection is not limited only to the explanation of this specific embodiment.
Claims (5)
1. novel biology artificial hepatocyte reactor, lid is in the shell upper end, the culture fluid outlet is in the shell lower end, it is characterized in that two layers and two layers are symmetrical arranged with the upper flat plate center of gravity, in the middle of every layer of flat board circular hole is set, the surface is provided with two above apertures, and has spun one deck chitosan nano fiber support at planar surface, flat board is fixed on the hollow stent by center hole, and the hollow stent side is provided with side opening.
2. novel biology artificial hepatocyte reactor according to claim 1 is characterized in that the hollow stent upper end is provided with opening, lower end closed.
3. novel biology artificial hepatocyte reactor according to claim 1 is characterized in that side opening that the hollow stent side is provided with between every two-layer flat board, and in the surface of every layer of flat board.
4. novel biology artificial hepatocyte reactor according to claim 1 is characterized in that two layers and two layers equate that with the distance between per two layers of flat board in the upper flat plate be 4mm, every layer of slab-thickness is 2mm.
5. novel biology artificial hepatocyte reactor according to claim 1 is characterized in that the aperture on every layer of planar surface is diameter 1cm, and adjacent aperture pitch is from being 2cm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200810124260 CN101342099B (en) | 2008-07-04 | 2008-07-04 | Biology artificial hepatocyte reactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200810124260 CN101342099B (en) | 2008-07-04 | 2008-07-04 | Biology artificial hepatocyte reactor |
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| Publication Number | Publication Date |
|---|---|
| CN101342099A true CN101342099A (en) | 2009-01-14 |
| CN101342099B CN101342099B (en) | 2012-03-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200810124260 Expired - Fee Related CN101342099B (en) | 2008-07-04 | 2008-07-04 | Biology artificial hepatocyte reactor |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250766A (en) * | 2011-06-22 | 2011-11-23 | 南京医科大学附属南京第一医院 | Hepatocyte large-scale culturing and freezing device |
| CN103100119A (en) * | 2013-01-24 | 2013-05-15 | 中山大学 | Artificial liver bioreactor |
| WO2017143640A1 (en) * | 2016-02-26 | 2017-08-31 | 广州洁特生物过滤股份有限公司 | Cell culture apparatus and method |
| CN109136090A (en) * | 2018-02-06 | 2019-01-04 | 上海微知卓生物科技有限公司 | A kind of bioreactor |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0402272B1 (en) * | 1989-06-09 | 1995-10-04 | Terumo Kabushiki Kaisha | Cell-culturing substrate, cell-culturing substrate unit bioreactor and extracorporeal circulation type therapeutic apparatus |
| AU5757100A (en) * | 1999-06-21 | 2001-01-09 | General Hospital Corporation, The | Methods and devices for cell culturing and organ assist systems |
| CN100556381C (en) * | 2007-08-17 | 2009-11-04 | 浙江大学 | Filling bracket perfusion type bioreactor for artificial liver |
-
2008
- 2008-07-04 CN CN 200810124260 patent/CN101342099B/en not_active Expired - Fee Related
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102250766A (en) * | 2011-06-22 | 2011-11-23 | 南京医科大学附属南京第一医院 | Hepatocyte large-scale culturing and freezing device |
| CN102250766B (en) * | 2011-06-22 | 2014-01-29 | 南京医科大学附属南京第一医院 | Apparatus for large-scale culture and cryopreservation of hepatocytes |
| CN103100119A (en) * | 2013-01-24 | 2013-05-15 | 中山大学 | Artificial liver bioreactor |
| WO2017143640A1 (en) * | 2016-02-26 | 2017-08-31 | 广州洁特生物过滤股份有限公司 | Cell culture apparatus and method |
| US11028356B2 (en) | 2016-02-26 | 2021-06-08 | Guangzhou Jet Bio-Filtration Co., Ltd. | Cell culture apparatus and method |
| CN109136090A (en) * | 2018-02-06 | 2019-01-04 | 上海微知卓生物科技有限公司 | A kind of bioreactor |
| CN109136090B (en) * | 2018-02-06 | 2025-04-01 | 上海微知卓生物科技有限公司 | A bioreactor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101342099B (en) | 2012-03-14 |
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