CN205339692U - Artifical liver spends cytoskeleton bioreactor - Google Patents
Artifical liver spends cytoskeleton bioreactor Download PDFInfo
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- CN205339692U CN205339692U CN201620061507.2U CN201620061507U CN205339692U CN 205339692 U CN205339692 U CN 205339692U CN 201620061507 U CN201620061507 U CN 201620061507U CN 205339692 U CN205339692 U CN 205339692U
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Abstract
The utility model discloses an artifical liver spends cytoskeleton bioreactor, include the bioreactor shell, remove the cytoskeleton, fill support and liquid access & exit, the bioreactor shell includes upper portion and lower part, and upper portion and lower part are hollow structure, and the second cavity is with threaded connection component columniform content chamber in first cavity upper portion in and the lower part, the top middle zone on upper portion is provided with content chamber liquid outlet, and the bottom central authorities region of lower part is provided with content chamber liquid main entrance, liquid main entrance branch becomes a liquid inlet and the 2nd liquid inlet, a liquid inlet is connected to the liver and removes cytoskeleton liquid inlet, the 2nd liquid inlet is connected to the packing support, the utility model discloses can simulate perfusion in vivo, the perfusion is even, reduces dead space, dead space, can reduce the shearing force that the liver cell receives, the three -dimensional growing environment of simulation hepatocyte growth increases the liver cell total amount among the bioreactor.
Description
Technical field
This utility model belongs to field of biomedicine technology, relates to a kind of armarium, specifically a kind of Biotype artificial liver or hybrid artificial liver Acellularized valve bioreactor.
Background technology
Liver failure internal medicine conservative treatment poor effect, mortality rate is higher, artificial liver is liver failure critical treatment means, it includes Non-biotype artificial liver, Biotype artificial liver and hybrid artificial liver: non-ecology phenomena can only the Detoxication of temporary transient compensatory liver to a certain extent, the synthesis of liver, metabolic function and bioconversion function can not be substituted completely, therefore it does not have a positive effect in improving chronic liver failure patient's long-term prognosis, thus it is the focus of research at present closer to the Biotype artificial liver of human liver's physiological function and hybrid artificial liver；Bioreactor provides good living environment in vitro for hepatocyte, and is blood plasma and the hepatocyte of the treatment target place that carries out mass exchange, is bioartificial liver or the core apparatus of mixed type liver；Hollow-fiber bioreactor is current most study bioreactor so far, but its to there is cell distribution uneven, cell adhesion rate is low and poor activity, and the shortcoming such as semipermeable membrane obstruction, so people are constantly researching and developing various new-type bioreactor；Development along with tissue engineering technique and material science, it has been found that kinds of artificial synthetic material, modifies macropore chitosan stent such as galactose and can promote growth and the function of hepatocyte preferably；Zoopery is pointed out, support rack type bioreactor is built based on these artificial materials, liver failure is had curative effect definitely, but these support rack type bioreactors there is also many defects, thus constraining the performance of its curative effect, as easily formed dead space, dead space, liquid stream is uneven, liquid flowing resistance is big；In recent years, it has been found that liver organization goes cell, artery-sparing knot hoof tissue tract, is accordingly changed into biological support, after again implanting hepatocyte from portal system, and by Portal system perfusion culture fluid, liquid can along the blood vessel tract perfusion retained；And such support can provide the three dimensional growth environment of simulation tumor growth for hepatocyte, thus significantly improving hepatocellular function；Should " tissue engineering artificial liver " transplant to liver failure animal, it is shown that good therapeutic effect.These breakthroughs have established solid foundation for development of new bioreactor for artificial liver.
Utility model content
The purpose of this utility model be in that to provide a kind of can the artificial liver Acellularized valve bioreactor of liver blood perfusion and hepatic cell growth three dimensional growth environment in analogue body, with the problem solving to propose in above-mentioned background technology.
For achieving the above object, this utility model provides following technical scheme:
A kind of artificial liver Acellularized valve bioreactor, including bioreactor shell, Acellularized valve, filling bracket and liquid discharge entrance；Described bioreactor shell includes upper and lower, and the junction between upper and lower adopts threaded；Top and bottom are hollow structure, and the first cavity in top is constituted cylindrical content cavity with the lower thread of the second cavity in bottom to threaded by top screw thread；The crown center region on described top is provided with content cavity liquid outlet, and the bottom central zones of bottom is provided with content cavity liquid main entrance；Liquid main entrance branch becomes first liquid entrance and second liquid entrance；Described first liquid entrance is connected to liver Acellularized valve liquid inlet；Described second liquid entrance is connected to filling bracket.
As further program of the utility model: described bioreactor shell is cylindrical.
As this utility model further scheme: described liquid outlet arranges liquid outlet switch.
As this utility model further scheme: described liquid main entrance place arranges liquid main entrance switch.
As this utility model further scheme: the junction of described first liquid entrance and Acellularized valve is provided with circular fixture.
As this utility model further scheme: described first liquid entrance and second liquid porch are provided with for controlling first liquid entrance and the liquid inlet valve of second liquid Inlet fluid flow.
As this utility model further scheme: described filling bracket porosity is 90%, between average pore is 100-200 μm, described filling bracket is that macropore chitosan stent modified by galactose.
As this utility model further scheme: described liver Acellularized valve liquid inlet is the portal vein of cell liver and branch, Hepatic artery or hepatic vein and branch thereof.
Compared with prior art, the beneficial effects of the utility model are: in this utility model, bioreactor is divided into upper and lower, and two parts are combined into reactor entirety by screw thread compact siro spinning technology, and this open structure can load Acellularized valve to reactor more easily；Sealing function is played in screw thread linking between upper and lower, and can bear bigger pressure, it is prevented that liquid oozes out from content cavity；First liquid entrance is connected with liver Acellularized valve liquid inlet, and junction arranges circular fixture so that the two is combined closely more, it is prevented that leakage；Remain the original blood vessel of liver and connective tissue tract due to Acellularized valve, therefore blood plasma enters support from liver Acellularized valve liquid inlet, it is possible to simulate perfusion in vivo, it is achieved relatively uniform perfusion, and reduce dead space, dead space；In addition, this utility model utilizes hand-stuff timbering material to fill reactor content cavity, both can fix Acellularized valve, reduces shearing force suffered by hepatocyte, growing environment can be provided for part of hepatocytes again as conventional stent type reactor, thus the hepatocyte total amount increased in bioreactor.
Accompanying drawing explanation
Fig. 1 is perspective view of the present utility model.
Fig. 2 is superstructure schematic diagram of the present utility model.
Fig. 3 is substructure schematic diagram of the present utility model.
Fig. 4 is the external system supplymentary device schematic diagram of this utility model.
Wherein, 1-liquid outlet；2-liquid outlet switchs；3-bioreactor shell；4-filling bracket；5-liver Acellularized valve liquid inlet；6-second liquid entrance；7-liquid main entrance；8-liquid main entrance switchs；9-first liquid entrance；10-circular fixture；11-junction；12-Acellularized valve；13-content cavity；14-top；15-lower thread；16-the second cavity；17-bottom；18-top screw thread；19-the first cavity；20-treatment target；21-the first blood pump；22-plasma separator；23-the second blood pump；24-oxygenator；25-immunoadsorption device；26-the 3rd blood pump；27-artificial liver Acellularized valve bioreactor；28-circulatory pool.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the technical scheme of this patent is described in more detail.
Referring to Fig. 1-3, a kind of artificial liver Acellularized valve bioreactor, including bioreactor shell 3, Acellularized valve 12, filling bracket 4 and liquid discharge entrance；Described bioreactor shell 3 is cylindrical, and bioreactor shell 3 includes top 14 and bottom 17, and the junction 11 between top 14 and bottom 17 adopts threaded；Top 14 and bottom 17 are hollow structure, and the first cavity 19 in top 14 is constituted cylindrical content cavity 13 with the lower thread 15 of the second cavity 16 in bottom 17 to threaded by top screw thread 18；The crown center region on described top 14 is provided with content cavity liquid outlet 1, and liquid outlet 1 place arranges liquid outlet switch 2；The bottom central zones of described bottom is provided with content cavity liquid main entrance 7, and liquid main entrance 7 place arranges liquid main entrance switch 8；Liquid main entrance 7 branch becomes first liquid entrance 9 and second liquid entrance 6；First liquid entrance 9 is connected to liver Acellularized valve liquid inlet 5, and the junction of first liquid entrance 9 and Acellularized valve 12 is provided with circular fixture 10；Described second liquid entrance 6 is connected to filling bracket 4；Described first liquid entrance 9 and second liquid entrance 6 place are provided with for controlling first liquid entrance 9 and the liquid inlet valve of second liquid entrance 6 fluid flow.
In this utility model, bioreactor shell 3 adopts the good organic material of biocompatibility to constitute, and such as transparent Merlon, good biocompatibility, and can observe liquid storage tank and the height of content cavity 13 liquid level easily.
In this utility model, Acellularized valve 12 is make to spend the cell technology whole liver or part hepatic tissue to human or animal to remove cell, the biological support of artery-sparing and connective tissue tract, liver Acellularized valve liquid inlet 5 is go to the portal vein of cell liver and branch, Hepatic artery or hepatic vein and branch thereof；Liver Acellularized valve liquid inlet 5 is the original vascular tissue of liver, it is connected with the first liquid entrance 9 of bioreactor, liquid enters Acellularized valve 12 from liver Acellularized valve liquid inlet 5, it is possible to simulated liver blood flow, and Acellularized valve 12 is carried out perfusion.
Content cavity 13 liquid outlet 1 of described Acellularized valve 12 is arranged on reactor head, and liquid main entrance 7 is arranged on reactor bottom, according to principle of hydrodynamics, is more conducive to liquid flowing.
Described filling bracket 4 is good biocompatibility, being the timbering material of solid-state by physical and chemical reaction from liquid conversion, porosity is 90%, between average pore is 100-200 μm, and in liquid curing process, the structure influence of Acellularized valve 12 is little, for instance macropore chitosan stent modified by galactose.
In this utility model, hold hepatocyte or hepatocyte/Interstitial cell in Acellularized valve 12 and filling bracket 4, and provide good three-dimensional environment for its growth.
Bioreactor volume of the present utility model can scale up and reduce, to adapt to different size of Acellularized valve 12 and the different treatment target of body weight；Bioreactor of the present utility model also can adopt multiple reactors in series or parallel connection, the hepatocyte total amount required to expand treatment.
Refer to Fig. 4, to treat severe viral hepatitis, tell about operation principle of the present utility model in detail:
(1) to bioreactor sterilizing of the present utility model before using, this bioreactor top 14 turned on by aseptic super-clean bench or hundred grades of laboratorys, the second cavity 16 is made to open wide, Acellularized valve 12 is loaded in the second cavity 16, liver Acellularized valve liquid inlet 5 is connected with first liquid entrance 9, and with circular fixture 10, both are fixed, it is prevented that leakage, after Acellularized valve 12 loading, the top 14 of reactor is tightened again with bottom 17；
(2) liquid main entrance switch 8 and liquid outlet switch 2 are regulated, first liquid entrance 9 is closed, second liquid entrance 6 opens, liquid outlet 1 is open, liquid is formed to the man-made support material of injection in reactor content cavity by blood pump, until liquid level is higher than Acellularized valve top, forming liquid-solidization measure according to existing man-made support material, man-made support material forms liquid and becomes the loose porous filling bracket 4 of solid-state, and Acellularized valve is played fixation by the latter.
(3) liquid main entrance switch and liquid outlet switch are regulated, make first liquid entrance 9 open, second liquid entrance 6 switch closes, liquid outlet 1 is open, by blood pump from first liquid entrance 9, a certain amount of hepatocyte suspension or hepatocyte/Interstitial cell suspension are injected in liver Acellularized valve liquid inlet 5 in Acellularized valve 12, then, regulate liquid main entrance switch, first liquid entrance 9 is closed, second liquid entrance 6 is open, liquid outlet 1 is open, a certain amount of hepatocyte suspension or hepatocyte/Interstitial cell suspension is injected from second liquid entrance 6 to filling bracket 4 by blood pump, will be loaded with the reactor of cell and put into cultivation in cell culture incubator, and the cell culture fluid that constantly perfusion oxygen content is suitable, good environment is provided to Growth of Cells, be cultured to cell quality and quantity reach treatment needed for；
(4) by, shown in Fig. 4, connecting each pipeline, with normal saline, pipeline is carried out liquid preliminary filling, give treatment target 20 a certain amount of normal saline, the blood volume of outflow during with prosthodontic treatment；
(5) after treatment starts, the arterial blood for the treatment of target 20 pumps into plasma separator 22 through the first blood pump 21, the blood plasma being separated enters oxygenator 24 and carries out oxygenate, thus obtaining suitable partial pressure of oxygen, enter the A chamber of circulatory pool 28, blood plasma in the A chamber of circulatory pool 28, artificial liver Acellularized valve bioreactor 27 is pumped into internal by the 3rd blood pump 26, regulate liquid main entrance switch 8, the flow rate of liquid entering Acellularized valve 12 and filling bracket 4 can be controlled, the blood plasma for the treatment of target 20 carries out mass exchange with the hepatocyte in Acellularized valve 12 and filling bracket 4, then flow out through liquid outlet 1, enter the B chamber of circulatory pool 28, part blood plasma in the B chamber of circulatory pool 28, by mixing with the blood either directly through plasma separator 22 after immunoadsorption device 25, through the second blood pump 23, by in defeated time treatment target 20 body of vein end；The B chamber of circulation 28 separately there is part blood plasma can enter in the A chamber of circulatory pool 28, artificial liver Acellularized valve bioreactor 27 is pumped into internal by the 3rd blood pump 26, so that part plasma circulation perfusion is in reactor, the blood plasma being beneficial to treatment target 20 fully acts on the hepatocyte in bioreactor；
(6) treatment closes to an end, and when entrance blood plasma is fed back into 20 stage for the treatment of target, stops drawing blood from treatment target arterial end；Adjust liquid outlet switch 2, make bioreactor content cavity 13 communicate with ambient atmosphere；Adjust the direction of the 3rd blood pump 26 so that the blood plasma in bioreactor content cavity 13 returns the A intracavity of circulatory pool 28；Blood plasma in the A chamber of circulatory pool 28 and B chamber, by after immunoadsorption device 25 through the second blood pump 23, by defeated time treatment target 20 body of vein end.
Above the better embodiment of this patent is explained in detail, but this patent is not limited to above-mentioned embodiment, in the ken that one skilled in the relevant art possesses, it is also possible under the premise without departing from this patent objective, make various change.
Claims (8)
1. an artificial liver Acellularized valve bioreactor, including bioreactor shell (3), Acellularized valve (12), filling bracket (4) and liquid discharge entrance；It is characterized in that: described bioreactor shell (3) includes top (14) and bottom (17), the junction (11) between top (14) and bottom (17) adopts threaded；Top (14) and bottom (17) are hollow structure, and the first cavity (19) in top (14) is constituted cylindrical content cavity (13) with the lower thread (15) of the second cavity (16) in bottom (17) to threaded by top screw thread (18)；The crown center region on described top (14) is provided with content cavity liquid outlet (1), and the bottom central zones of bottom is provided with content cavity liquid main entrance (7)；Liquid main entrance (7) branch becomes first liquid entrance (9) and second liquid entrance (6)；Described first liquid entrance (9) is connected to liver Acellularized valve liquid inlet (5)；Described second liquid entrance (6) is connected to filling bracket (4).
2. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that described bioreactor shell (3) is cylindrical.
3. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that described liquid outlet (1) place arranges liquid outlet switch (2).
4. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that described liquid main entrance (7) place arranges liquid main entrance switch (8).
5. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that the junction of described first liquid entrance (9) and Acellularized valve (12) is provided with circular fixture (10).
6. artificial liver Acellularized valve bioreactor according to claim 1, it is characterized in that, described first liquid entrance (9) and second liquid entrance (6) place are provided with for controlling first liquid entrance (9) and the liquid inlet valve of second liquid entrance (6) fluid flow.
7. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that described filling bracket (4) porosity is 90%, between average pore is 100-200 μm, described filling bracket (4) modifies macropore chitosan stent for galactose.
8. artificial liver Acellularized valve bioreactor according to claim 1, it is characterised in that described liver Acellularized valve liquid inlet (5) is go to the portal vein of cell liver and branch, Hepatic artery or hepatic vein and branch thereof.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201620061507.2U CN205339692U (en) | 2016-01-22 | 2016-01-22 | Artifical liver spends cytoskeleton bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201620061507.2U CN205339692U (en) | 2016-01-22 | 2016-01-22 | Artifical liver spends cytoskeleton bioreactor |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108588006A (en) * | 2018-05-10 | 2018-09-28 | 华东理工大学 | A kind of biological support and its preparation method and application for liver cell dimensional culture |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108588006A (en) * | 2018-05-10 | 2018-09-28 | 华东理工大学 | A kind of biological support and its preparation method and application for liver cell dimensional culture |
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| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160629 Termination date: 20220122 |
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| CF01 | Termination of patent right due to non-payment of annual fee |