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Bioreactor of artificial liver

A bioreactor and artificial liver technology, applied in biochemical instruments, biochemical equipment and methods, suction devices, etc., can solve the problems of decreased biological activity, death, and shedding of liver cells, so as to promote reproduction and growth, and improve biological activity , the effect of broad application prospects

Inactive Publication Date: 2007-10-10
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0004] The density of hepatocytes in the current bioartificial liver is generally 5-8×10 8 cells / m 2 Between, and the hepatocyte density of human liver is 2~3×10 10 cells / m 2 There is still a big gap. Therefore, the current artificial liver cannot meet the blood purification needs of an adult
Moreover, the hepatic spheroids of the current biological artificial liver are easy to fall off from the cell matrix with the flow of the culture medium, resulting in uneven distribution of hepatocytes and a decrease in the number of hepatocytes.
Liver cells have a large demand for oxygen, but the existing bioartificial livers have the disadvantage of insufficient oxygen supply, resulting in reduced biological activity of liver cells or even death
The above reasons seriously affect the clinical efficacy of artificial liver
No reports or patents have been found on the improvement of artificial liver bioreactors using nanofibrous scaffolds

Method used

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preparation example Construction

[0017] 1. Preparation of nanofibrous scaffolds: select different solvents to dissolve polymers (alginate, polylysine, chitosan, agarose, polyvinyl alcohol, etc.) to prepare electrospinning solutions. According to the different properties of the polymer solution, different electrospinning conditions (voltage, receiving distance, injection speed) are formulated, and then spinning is carried out. Adjustable shape and thickness. The nanofiber scaffolds of different materials are modified and sterilized accordingly to prepare nanofiber scaffolds that can be placed in cell culture fluid as cell growth substrates.

[0018] 2. Structural design of hollow fiber and nanofiber support: flatten the nanofiber non-woven fabric support, arrange polysulfone hollow fibers in sequence on the support (with a distance of 0.5mm to 2mm), and then curl the nanofiber support to wrap the hollow fiber in it. Inside, the core components of the bioreactor are made. One hollow fiber is selected at inter...

example 1

[0020] Example 1: This new type of bioreactor was fabricated using alginate as the raw material of the nanofiber scaffold.

[0021] 1. Preparation of nanofiber scaffold: (1) Preparation of electrospinning solution: Sodium alginate was dissolved in deionized water to prepare concentration as mass ratio W 海藻酸钠 :W 去离子水 = 4% solution. Polyethylene oxide (Mw=900kD) was dissolved in deionized water to prepare a concentration of mass ratio W 聚氧化乙烯 :W 去离子水 = 4% solution. Then the two solutions are mixed in the volume ratio V 海藻酸钠溶液 :V 聚氧化乙烯溶液 = Mix at a ratio of 8:2, stir at room temperature for 100 min until uniformly mixed, and obtain a mixed solution of sodium alginate and polyethylene oxide. Then by volume ratio V 表面活性剂 :V 混 合溶液 =0.5% ratio Add surfactant Triton X-100, keep stirring for 10min. Then according to the volume ratio V 助溶剂 :V 混合溶液 The co-solvent dimethyl sulfoxide was added at a rate of =10%. Stirring was continued for 60 min at room temperature. That is, a...

example 2

[0024] Example 2: Using chitosan as the raw material of the nanofiber scaffold to make this new bioreactor.

[0025] 1. Preparation of nanofiber support: (1) Preparation of electrospinning solution: dissolving chitosan (Mw=190kD, Deacetylation=85%) in an acetic acid solution with a mass ratio of 5% is prepared into a concentration of mass ratio W 壳聚糖 :W 醋酸溶液 = 2% solution. Polyethylene oxide (Mw=900kD) is dissolved in the acetic acid solution that the mass ratio is 5% and is prepared into the concentration that the mass ratio is W 聚氧化乙烯 :W 醋酸溶液 = 3% solution. Then the two solutions are mixed in the volume ratio V 壳聚 糖溶液 :V 聚氧化乙烯溶液 = 9: 1 ratio mixing, stirring at room temperature for 100min until mixing evenly, to obtain a mixed solution of chitosan and polyethylene oxide. Then by volume ratio V 表面活性剂 :V 混合溶液 =0.3% ratio Add surfactant Triton X-100, keep stirring for 10min. Then according to the volume ratio V 助溶剂 :V 混合溶液 The co-solvent dimethylformamide was added a...

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Abstract

This invention relates to an artificial live bioreactor with nanofiber scaffold material as the culture medium for liver cells. A plasma inlet and an oxygen inlet are set at one end of the bioreactor hull, while a plasma outlet and an oxygen outlet are set at the other end. A nutrient solution inlet and an outlet are set at both ends of one side of the bioreactor hull, respectively. A culture medium composed of nanofiber scaffold and hollow fibers is set in the bioreactor hull. The nanofiber scaffold and the hollow fibers form coiled sandwich structure, with the nanofiber scaffold coiled into spiral drum and the hollow fibers encapsulated in the interlayer. The liver cell aggregates are adhered to the hollow fibers. An oxygen passage is set in the bioreactor to realize real-time oxygen supplement.

Description

technical field [0001] The invention relates to a bioreactor for a bioartificial liver using a nanofiber scaffold material as a substrate for culturing hepatocytes, and belongs to the technical field of artificial liver support systems. Background technique [0002] As an effective adjuvant treatment technology for hepatic insufficiency, liver failure or related diseases, the artificial liver has been widely used in clinical practice. The artificial livers currently used in clinical practice mainly include three types: non-biological artificial liver, biological artificial liver, and hybrid artificial liver. liver. Among them, the biological artificial liver has the most remarkable curative effect in the clinical application of treating patients with liver diseases. The biological artificial liver generally refers to the in vitro biological reaction system with artificially cultured liver cells as the basic components. It not only has the specific detoxification function of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12M3/00A61F2/00A61M1/18
Inventor 顾忠泽冯章启付德刚
Owner SOUTHEAST UNIV
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