Three-dimensional liver cell culture bioreactor

Abstract

Disclosed is a 3-D bioreactor to culture hepatic cells, comprising a culture cavity provided with a cell feeding port and a vent, an inflow cavity with a culture fluid inlet and an outflow cavity with a culture fluid outlet which are arranged next to the culture cavity. A plurality of hollow fibers are arranged inside the culture cavity, each with one end communicated with the inflow cavity and the other end communicated with the outflow cavity, forming a culture fluid flow passage which is communicated with the culture cavity through the tiny holes on the hollow fibers. The invention is characterized in that a 3-d bracket with a plurality of holes is arranged inside the culture cavity. The invention can provide a growth and culture condition that accords better with the physiological environment for the hepatic cells, which is good for culturing dense hepatic cells with high activity so as to ensure the therapeutic effect of a bio-artificial liver with the hepatic cells as the core.

Description

technical field [0001] The patent of the present invention relates to a medical device, especially a core device that can be used as a core device of an in vitro bioartificial liver support system, an experimental device or a biological preparation device, and can also be used for experimental research and extraction of cultured liver cells A small production facility for cellular products. Background technique [0002] The existing clinical bioreactor is a hollow fiber reactor, its structure is exactly the same as that of the hemodialyzer, but the material, pore size and molecular interception of the semipermeable membrane used are different. The hollow fiber reactor is the A bundle (50-100) of hollow fibers is sealed in a transparent organic material shell, which is divided into inner and outer chambers by the hollow fibers, which are used to place liver cells and flow patient blood respectively. With the help of the hollow fiber semi-permeable membrane, Carry out two-way...

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Problems solved by technology

[0003] There are many defects in the practical application of this mode of reactor: 1. In terms of structure, the hollow fibers of the traditional ordinary reactor are arranged in parallel and densely in a bundled column shape, and the culture environment of liver cells is less considered. It is incompatible with material transport and exchange; 2. In terms of cell culture, it can only provide two-dimensional culture for liver cells, but cannot provide a three-dimensional culture microenvironment, which is not conducive to the tissue culture and functional recovery of liver cells in vitro; 3. In cell culture In terms of distribution, when added cells are often deposited at the bottom of the reactor due to the action of gravity, they cannot be evenly distributed among the hollow fibers. Even if the cells can reach the middle of the fiber bundle, they will be inactivated due to insufficient oxygen supply; 4. In clinical liver support , the traditional reactor is difficult to play its due biological function and role due to the small amount of cells (generally only 1% to 5% of the amount of adult hepatocytes), low viability, and poor function

[0005] The bioreactor has the following disadvantages: 1. From the structure of the reactor, when it is used as a bioartificial liver for research or clinical use, the patient's blood or plasma directly contacts the liver cells in the three-dimensional scaffold, without any immune barrier effect, no It is beneficial to protect the immune safety of patients, and it is difficult to promote its use in clinical practice; 2. When culturing hepatocytes, in terms of nutrient supply, the nutrient solution flows through the gap between the three-dimensional scaffold and the liver cells. Gradually smaller, the circulating nutrient solution is easily blocked, resulting in poor circulation, uneven perfusion, and limited nutrient supply; 3. The blood, plasma or nutrient solution is circulated under the action of the pump, so that the cells are directly affected by the Larger shear force can easily cause damage to liver cells

[0006] Therefore, the above defects are one of the important factors that make it difficult to further improve the curative effect of bioartificial liver in the treatment of liver failure.

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