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Artificial liver reactor as well as preparation method and applications thereof

A reactor and artificial liver technology, applied in the field of biomedicine, can solve the problems of small effective exchange area, low cell load, uneven cell distribution, etc., and achieve the effect of solving uneven growth of liver cells and ensuring uniformity.

Pending Publication Date: 2017-05-10
SHANGHAI CELLIVER BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Therefore, aiming at technical problems such as low cell load, small effective exchange area, uneven cell distribution, and low metabolic exchange efficiency in the bioreactor in the prior art, the purpose of the present invention is to provide a bioreactor with high cell load and effective exchange area. Artificial liver reactor with large size, uniform cell distribution and high metabolic exchange efficiency

Method used

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  • Artificial liver reactor as well as preparation method and applications thereof
  • Artificial liver reactor as well as preparation method and applications thereof
  • Artificial liver reactor as well as preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Artificial Liver Reactor

[0039] figure 1 Shown is an artificial liver reactor according to a preferred embodiment of the present invention, which includes an integrated circuit controller 1 and a bioreactor module 2 .

[0040] One side of the reactor biomodule 2 is provided with an input main pipe 3, and the other side is provided with an output main pipe 4, and three 1000mL cell culture bottles (respectively A, B, C) are arranged in parallel between the input main pipe 3 and the output main pipe 4. Such as figure 2 As shown, the bottle cap 5 on the top of the cell culture bottle is provided with a ventilation filter 6 of 0.22 microns; a sampling port 7 of 2×3 cm is arranged on the side wall of the cell culture bottle; The room is an isolation area, which is filled with bilirubin adsorption resin 8; the two sides of the bottom of the cell culture bottle are respectively provided with an input tube 9 and an output tube 10, and the input tubes 9 of the cell...

Embodiment 2

[0042] Example 2 Preparation of artificial liver reactor in Example 1

[0043] (a) Liver cell inoculation, immerse the sheet-shaped carrier in PBS solution with pH 7.4 (purchased by Sigma) for hydration for 24-72 hours, and then hydrate the hydrated sheet-shaped carrier in 10-200 μg / mL collagen Cover at room temperature for 30min to 2h, absorb excess liquid, wash with PBS or serum-free medium for 3 to 4 times, and then mix with hepatocytes (HepG2 / C3A cells, purchased from ATCC) and culture medium (DMEM medium, purchased from ATCC) mix, the mixing ratio is 10 6 ~10 8 Hepatocytes / 1g sheet-shaped carrier / 100mL culture medium, shake culture for 30min~2h to make hepatocytes attach to the sheet-shaped carrier to complete inoculation;

[0044] (b) liquid-gas interactive culture, adding the sheet-shaped carrier and medium after inoculation in step (a) into each cell culture bottle of the artificial liver reactor assembled, sealing the bottle cap 5 and inputting the main pipe 3 inlet...

Embodiment 3

[0046] Example 3 Circulating perfusion bioartificial liver support system

[0047] Such as Figure 4 As shown, the circulating perfusion bioartificial liver support system includes a conventional blood cell-plasma separator 12 and an artificial liver reactor 13 of the present invention. The plasma circulation outlet port of the blood cell-plasma separator 12 is connected with the input main pipe 3 of the artificial liver reactor 13, and the output main pipe 4 of the artificial liver reactor 13 is connected back to the plasma circulation to form a circulation loop.

[0048] Preferably, the system also includes a plasma dialyzer, a gas input device, a regulating fluid input device, a constant temperature heater, and a central controller for controlling each part of the system.

[0049] Blood cell-plasma separator, plasma dialyzer, gas input device, regulating fluid input device, and constant temperature heater are all commonly used equipment in the existing bioartificial liver ...

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Abstract

The invention discloses an artificial liver reactor. The artificial liver reactor comprises an input header pipe, an output header pipe, and one or more cell culture bottles connected in parallel or in series, wherein the cell culture bottles are connected between the input header pipe and the output header pipe, an input pipe and an output pipe are arranged at two sides of the bottom of each cell culture bottle, and a peristaltic pump is arranged on each input pipe; a separation net is arranged in each cell culture bottle, the part between the separation net and the bottom of each cell culture bottle is filled with a filler with an adsorption function, a flake-shaped carrier is loaded to each separation net, and hepatic cells attach to the flake-shaped carriers. For the artificial liver reactor, due to the arrangement of the peristaltic pumps and the flake-shaped carriers, the cell loading capacity, the effective exchange area and the metabolism exchange efficiency of the artificial liver reactor can be effectively improved. The invention further discloses a method for preparing the artificial liver reactor, and a circular pouring bioartificial liver support system comprising the artificial liver reactor.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a liquid-gas interactive bioartificial liver reactor and a preparation method thereof, and also relates to a circulating perfusion bioartificial liver support system containing the artificial liver reactor. Background technique [0002] The liver is one of the most important vital organs of the body, with a complex structure and various physiological functions. However, liver failure seriously affects people's health. Liver transplantation is a better way to fundamentally treat end-stage liver disease and liver failure. However, due to the limitations of donor liver shortage, xenograft failure, high cost and long-term use of immunosuppressants, a considerable number of patients still have Liver transplantation is not possible. Therefore, it is urgent to seek new methods for the treatment of liver diseases. The research on the bioartificial liver is a hot topic i...

Claims

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Application Information

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IPC IPC(8): A61M1/18
CPCA61M1/1621
Inventor 吴红平金晓芳曾敏杨秋蕊
Owner SHANGHAI CELLIVER BIOTECHNOLOGY CO LTD
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