CN101294136A - Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof - Google Patents
Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof Download PDFInfo
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- CN101294136A CN101294136A CNA2007100398466A CN200710039846A CN101294136A CN 101294136 A CN101294136 A CN 101294136A CN A2007100398466 A CNA2007100398466 A CN A2007100398466A CN 200710039846 A CN200710039846 A CN 200710039846A CN 101294136 A CN101294136 A CN 101294136A
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Abstract
The invention relates to a biological artificial liver cell growth assembly which is characterized in that the liver cell growth assembly includes multilayer non-woven fabric cloth; each non-woven fabric cloth layer contains a bio-material coating and has a hollow fiber layer on the surface; and the pitch between two adjacent non-woven fabric cloth layers is 10 to 100 microns. The biological artificial liver cell growth assembly has the advantages that the biological artificial liver reactor can enable liver cells to be uniformly distributed around the hollow fibers, and the layer pitch is reasonable to ensure the liver cells to grow for a longer period. The liver cells in compact arrangement by centrifugal perfusion can better perform functions of detoxification, transformation, etc. as the substitute of the liver during treatment. The biological artificial liver cell growth assembly can be used for culture and growth of liver cells or for substituting for the liver to carry out substitute treatment for liver failure patients or transit to liver transplantation.
Description
Technical field:
The present invention relates to a kind of bioartificial liver's cell field, be specifically related to biological artificial liver cell growth component and comprise the liver reactor of this growth module.
Background technology:
The prior biological artificial liver reactor substantially all is in research state, also is hollow fiber type mainly structurally.Because tubular fibre does not all have fixing except two ends, liver cell does not fixedly adhere to around tubular fibre yet, and cause the liver cell skewness, and the spacing of liver cell layer and tubular fibre is inhomogeneous, most of liver cells can not obtain effective oxygen supply, can't cultivate for a long time and effectively play a role.
Also begin one's study at present and make the tubular fibre layer keep rational interlamellar spacing, so that liver cell can be cultivated and effectively play a role for a long time, and because design problem, when liver cell is poured in bio-reactor, liver cell can not uniform distribution, thereby influence hepatocellular cultivation and function, reduced hepatocellular effective efficiency.
Summary of the invention:
One object of the present invention is to provide a kind of equally distributed biological artificial liver cell growth component of liver cell that can make.
To achieve these goals, technical scheme of the present invention is as follows: biological artificial liver cell growth component, it is characterized in that this liver cell growth assembly comprises multi-layer nonwoven fabrics, every layer of non-woven fabrics all contains the biomaterial coating, every layer of nonwoven surface has been equipped with the tubular fibre layer, and the spacing between the adjacent two layers non-woven fabrics is 10～100 microns.The tubular fibre layer multi beam hollow fiber conduit on non-woven fabrics that is arranged side by side wherein, all tubular fibre layers are provided with 500～10000 hollow fiber conduits altogether in this growth module.
Bioartificial liver's reactor of providing one can hold above-mentioned biological artificial liver cell growth component is provided another object of the present invention.
To achieve these goals, technical scheme of the present invention is as follows: a kind of bioartificial liver's reactor, comprise container body, it is characterized in that this container body one end is provided with the blood inlet, the other end is provided with the blood outlet, be provided with the liver cell perfusing hole at the container body sidewall, be provided with biological artificial liver cell growth component in this container body, the multilayer that comprises this biological artificial liver cell growth component contains the non-woven fabrics of biomaterial coating, nonwoven surface is equipped with compact arranged side by side multi beam hollow fiber conduit, one end of hollow fiber conduit is connected with the blood inlet, the other end of hollow fiber conduit is connected with the blood outlet, space between hollow fiber conduit and the non-woven fabrics forms exocoel, and exocoel is communicated with the liver cell perfusing hole.Wherein multi beam tubular fibre tube side-by-side closely is arranged on the non-woven fabrics, and all tubular fibre layers are provided with 500～10000 hollow fiber conduits altogether in this biological artificial liver cell growth component.This container body is a cylindrical container, and this multi-layer nonwoven fabrics is the nonwoven fabric roll of reeling along the hollow fiber conduit vertical direction, and the spacing of adjacent two layers non-woven fabrics is every 10～100 microns.Also can be another shape and structure, this container body be plate shaped container, the multi-layer nonwoven fabrics that this multi-layer nonwoven fabrics is arranged for tiling, and the spacing of adjacent two layers non-woven fabrics is every 10～100 microns.
Another object of the present invention is to provide a kind of method for preparing above-mentioned bioartificial liver's reactor.
To achieve these goals, technical scheme of the present invention is as follows: a kind of preparation method of bioartificial liver's reactor, may further comprise the steps: A, multi beam tubular fibre tube side-by-side closely are arranged on the non-woven fabrics that contains the biomaterial coating, and the quantity of hollow fiber conduit is 500～10000; B, this non-woven fabrics is reeled along the hollow fiber conduit vertical direction, hollow fiber conduit is concentrated and is fixed on the non-woven fabrics two ends, forms biological artificial liver cell growth component; C, this biological artificial liver cell growth component is placed in the cylindrical container body, this container body one end is provided with the blood inlet, the other end is provided with the blood outlet, be provided with the liver cell perfusing hole at the container body sidewall, one end of hollow fiber conduit is positioned at the blood inlet, the other end is positioned at the blood outlet, and wherein the space between hollow fiber conduit and the non-woven fabrics forms exocoel, and exocoel is communicated with the liver cell perfusing hole; D, with the closed at both ends of this container body, make the inner chamber of hollow fiber conduit and exocoel isolate; E, liver cell is filled in the exocoel by centrifugal method, liver cell is closely arranged wherein.
In the present invention, the passage that hollow fiber conduit provides blood flow to cross, containing the non-woven fabrics of biomaterial coating and the multilayer space of tubular fibre layer formation is that exocoel is used for holding liver cell.The appropriate distance that keeps each layer that non-woven fabrics and tubular fibre layer form, and tiling or be wound into multilayer can make the liver cell uniform distribution like this, bring into play maximum efficiency.The invention has the advantages that this bioartificial liver's reactor can make liver cell be evenly distributed on tubular fibre around, reasonably interlamellar spacing makes the liver cell can more secular growth.Can substitute functions such as the detoxifcation of liver, conversion in the better performance of when treatment by centrifugal dabbling compact arranged liver cell.The present invention can be used for hepatocellular incubation growth, also can be used for substituting the effect of liver, and the liver failure patient is carried out replacement therapy or carries out the transition to liver transplantation.
Description of drawings:
Fig. 1 is a kind of structural representation of biological artificial liver cell growth component
Fig. 2 is the structural representation that is used for holding the cylindrical transparent container of growth module among Fig. 1
Fig. 3 is the structural representation of another kind of biological artificial liver cell growth component
Fig. 4 is the structural representation that is used for holding the plate shaped container of growth module among Fig. 3
Embodiment:
Below in conjunction with drawings and Examples the present invention is elaborated.
As shown in Figure 1, biological artificial liver cell growth component is characterized in that this liver cell growth assembly comprises multi-layer nonwoven fabrics 1, and every layer of non-woven fabrics 1 all contains the biomaterial coating, every layer of non-woven fabrics 1 surface has been equipped with the tubular fibre layer, and the spacing between the adjacent two layers non-woven fabrics 1 is 10～100 microns.The tubular fibre layer multi beam hollow fiber conduit 2 on non-woven fabrics that is arranged side by side wherein, all tubular fibre layers are provided with 500～10000 hollow fiber conduits 2 altogether in this growth module.
The present invention also provides a kind of bioartificial liver's reactor, comprises a cylindrical transparent container 3 with a plurality of import and export, and inner biological artificial liver cell growth is set up.Two tops of container 3 are respectively equipped with blood inlet 4 and blood outlet 5, and the two ends of the cylinder side wall of container are respectively equipped with liver cell perfusing hole 7.With multi beam hollow fiber conduit 2 tight arranged distribution on the non-woven fabrics 1 that coating is handled, non-woven fabrics 1 is provided with a long strip shape notch 6, hollow fiber conduit 2 length directions are vertical with notch 6 length directions, along the side coiling that notch is arranged with the vertical direction of hollow fiber conduit 2 length directions, from a side direction of no notch, form the winding of non-woven fabrics 1 and hollow fiber conduit 2, the distance that keeps every layer is 10～100 microns, put into above-mentioned transparent vessel 3, again in the two ends sealing of the cylinder side wall of this winding and container 3.Like this, the inside of all hollow fiber conduits 2 is inner chamber; Space between the outside of hollow fiber conduit 2 and the non-woven fabrics 1 is communicated with by the cylindrical container of notch with container 3, surrounds an exocoel.3 two vertical mouths of container are respectively blood inlet 4 and outlet 5, link to each other with inner chamber; The cylinder side wall of container 3 is provided with liver cell perfusing hole 7, links to each other with exocoel.
According to one embodiment of present invention, select a square or rectangular non-woven fabrics 1 of handling through biological coating (polyamino acid urethane resin) for use, width can equally with hollow fibre filament length be that 240 mm wides, length are 500 millimeters.Hollow fiber conduit 2 closely is arranged on this non-woven fabrics 1, non-woven fabrics 1 is provided with a long strip shape notch 6, hollow fiber conduit 2 length directions are vertical with notch 6 length directions, edge and the vertical direction of hollow fiber conduit 2 length directions, there is a side of notch to reel from a side direction of no notch, keeping the spacing between the adjacent two layers non-woven fabrics 1 is 10～100 microns, two ends glue envelope with the non-woven fabrics winding, make the hollow fiber conduit two ends concentrate and be fixed on the non-woven fabrics two ends, make biological artificial liver cell growth component, get a transparent or semitransparent cylindrical container, these container 3 one ends are provided with blood inlet 4, the other end is provided with blood outlet 5, be respectively equipped with liver cell perfusing hole 7 at container body 3 sidewalls, biological artificial liver cell growth component is placed in this container, hollow fiber conduit 2 two ends lay respectively in blood inlet 4 and the blood outlet 5, then the blood inlet 4 and blood outlet 5 encapsulation of this container 3 are got up; It also can be another shape and structure, as shown in Figure 2, the non-woven fabrics 1 that closely is arranged with hollow fiber conduit 2 is tiled in the plate shaped container, 10～100 microns distance shops, every interval one deck, form multilayer, then multi-layer nonwoven fabrics two ends glue is sealed, make the hollow fiber conduit two ends be fixed on the non-woven fabrics two ends, make biological artificial liver cell growth component, this biological artificial liver cell growth component is encapsulated in both sides is provided with blood inlet 4 and blood outlet 5, the side is provided with in the plate shaped container of liver cell perfusing hole 7.So just make the bioartificial liver's reactor that holds the rational space structure of liver cell layer.Nutrient solution is imported this reactor from the blood inlet, liver cell is placed in the whizzer, rotation by whizzer pours into this reactor by centrifugal dabbling method from the liver cell perfusing hole with liver cell, it is closely arranged wherein, can make liver cell obtain sufficient nutriment growth and performance effective function.Wherein the material of hollow fiber conduit is polysulfone membrane or poly ethylene vinyl alcohol film, and the internal diameter of hollow fiber conduit is the 100-400 micron.
Though embodiment provided by the invention adopts cylindrical vessel, multi-layer nonwoven fabrics in the container is the nonwoven fabric roll of reeling along the hollow fiber conduit vertical direction, but be to be understood that, also can be as shown in Figure 2, adopt plate shaped container, the multi-layer nonwoven fabrics that tiling is arranged in the container, the spacing of adjacent two layers non-woven fabrics is every 10～100 microns.
The non-woven fabrics that biological coating (polyamino acid urethane resin) is handled is a prior art, does not repeat them here.Centrifugal perfusion also belongs to prior art, does not repeat them here.
Claims (10)
1, biological artificial liver cell growth component, it is characterized in that this liver cell growth assembly comprises multi-layer nonwoven fabrics, every layer of non-woven fabrics all contains the biomaterial coating, and every layer of nonwoven surface has been equipped with the tubular fibre layer, and the spacing between the adjacent two layers non-woven fabrics is 10～100 microns.
2, by the described biological artificial liver cell growth component of claim 1, it is characterized in that be arranged side by side multi beam hollow fiber conduit on non-woven fabrics of tubular fibre layer, all tubular fibre layers are provided with 500～10000 hollow fiber conduits altogether in this growth module.
3,, it is characterized in that multi-layer nonwoven fabrics is the nonwoven fabric roll of reeling along the hollow fiber conduit vertical direction by claim 1 or 2 described biological artificial liver cell growth components.
4,, it is characterized in that the multi-layer nonwoven fabrics that this multi-layer nonwoven fabrics is arranged for tiling by claim 1 or 2 described biological artificial liver cell growth components.
5, a kind of bioartificial liver's reactor, comprise container body, it is characterized in that this container body one end is provided with the blood inlet, the other end is provided with the blood outlet, be provided with the liver cell perfusing hole at the container body sidewall, be provided with biological artificial liver cell growth component in this container body, the multilayer that comprises this biological artificial liver cell growth component contains the non-woven fabrics of biomaterial coating, nonwoven surface is equipped with compact arranged side by side multi beam hollow fiber conduit, one end of hollow fiber conduit is connected with the blood inlet, the other end of hollow fiber conduit is connected with the blood outlet, and the space between hollow fiber conduit and the non-woven fabrics forms exocoel, and exocoel is communicated with the liver cell perfusing hole.
6, by the described bioartificial liver's reactor of claim 5, it is characterized in that this container body is a cylindrical container, this multi-layer nonwoven fabrics is the nonwoven fabric roll of reeling along the hollow fiber conduit vertical direction, and the spacing of adjacent two layers non-woven fabrics is 10～100 microns.
7, by the described bioartificial liver's reactor of claim 5, it is characterized in that this container body is plate shaped container, the multi-layer nonwoven fabrics that this multi-layer nonwoven fabrics is arranged for tiling, the spacing of adjacent two layers non-woven fabrics is 10～100 microns.
8, by the described bioartificial liver's reactor of claim 5, it is characterized in that multi beam tubular fibre tube side-by-side closely is arranged on the non-woven fabrics, all tubular fibre layers are provided with 500～10000 hollow fiber conduits altogether in this biological artificial liver cell growth component.
9, a kind of preparation method of bioartificial liver's reactor may further comprise the steps: A, multi beam tubular fibre tube side-by-side closely are arranged on the non-woven fabrics that contains the biomaterial coating, and the quantity of hollow fiber conduit is 500～10000; B, this non-woven fabrics is reeled along the hollow fiber conduit vertical direction, hollow fiber conduit is concentrated and is fixed on the non-woven fabrics two ends, forms biological artificial liver cell growth component; C, this biological artificial liver cell growth component is placed in the cylindrical container body, this container body one end is provided with the blood inlet, the other end is provided with the blood outlet, be provided with the liver cell perfusing hole at the container body sidewall, one end of hollow fiber conduit is positioned at the blood inlet, the other end is positioned at the blood outlet, and wherein the space between hollow fiber conduit and the non-woven fabrics forms exocoel, and exocoel is communicated with the liver cell perfusing hole; D, with the closed at both ends of this container body, make the inner chamber of hollow fiber conduit and exocoel isolate; E, liver cell is filled in the exocoel by centrifugal method, liver cell is closely arranged wherein.
10, press the preparation method of the described bioartificial liver's reactor of claim 9, it is characterized in that non-woven fabrics is provided with a long strip shape notch, the hollow fiber conduit length direction is vertical with the notch length direction, and the outside of hollow fiber conduit and the space between the non-woven fabrics are communicated with the cylindrical container of container by notch.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100398466A CN101294136A (en) | 2007-04-24 | 2007-04-24 | Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100398466A CN101294136A (en) | 2007-04-24 | 2007-04-24 | Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof |
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| CN101294136A true CN101294136A (en) | 2008-10-29 |
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| CNA2007100398466A Pending CN101294136A (en) | 2007-04-24 | 2007-04-24 | Biological artificial liver cell growth component, artificial liver reactor and preparation method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102409020A (en) * | 2010-09-26 | 2012-04-11 | 上海泰因生物技术有限公司 | Non woven/polyester fiber carriers for culturing cells and use method thereof |
| CN106222086A (en) * | 2016-07-29 | 2016-12-14 | 武汉仝干医疗科技股份有限公司 | Lint wire type bioartificial liver's reactor |
| CN111801410A (en) * | 2017-12-20 | 2020-10-20 | 尤尼沃尔塞尔斯技术股份公司 | Bioreactor and related methods |
| CN114456935A (en) * | 2016-11-09 | 2022-05-10 | 尤尼沃尔塞尔斯股份公司 | Cell growth substrate |
-
2007
- 2007-04-24 CN CNA2007100398466A patent/CN101294136A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102409020A (en) * | 2010-09-26 | 2012-04-11 | 上海泰因生物技术有限公司 | Non woven/polyester fiber carriers for culturing cells and use method thereof |
| CN106222086A (en) * | 2016-07-29 | 2016-12-14 | 武汉仝干医疗科技股份有限公司 | Lint wire type bioartificial liver's reactor |
| CN114456935A (en) * | 2016-11-09 | 2022-05-10 | 尤尼沃尔塞尔斯股份公司 | Cell growth substrate |
| US11827873B2 (en) | 2016-11-09 | 2023-11-28 | Univercells Technologies S.A. | Cell growth matrix |
| CN114456935B (en) * | 2016-11-09 | 2024-03-08 | 尤尼沃尔塞尔斯技术股份公司 | Cell growth matrix |
| CN111801410A (en) * | 2017-12-20 | 2020-10-20 | 尤尼沃尔塞尔斯技术股份公司 | Bioreactor and related methods |
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Open date: 20081029 |