Culture fluid gas/liquid and liquid/liquid exchanger for tissue engineering tissue bionic cultivation

Abstract

The invention discloses a culture fluid gas-to-fluid and fluid-to-fluid exchanger that is used for biomimetic tissue cultivation in tissue engineering, an inlet and an outlet of a circular culture fluid are arranged in the chamber of an exchanger shell, an inlet and an outlet of a fresh culture fluid are arranged on the shell, an inlet and an outlet that are used for the fresh culture fluid to pass through and for communicating a hydrophilic hollow fiber semi-permeable biomembrane bunch that implements fluid-to-fluid exchange of the circular culture fluid with the fresh culture fluid are arranged in the chamber, a gas outlet and a gas inlet are arranged on the shell, an inlet and an outlet that are used for gas to pass through and for communicating a hydrophobic hollow fiber semi-permeable biomembrane bunch that implements gas-to-fluid exchange of the circular culture fluid with the gas are arranged inside the chamber, and an airtight space is formed inside the chamber of the shell. Oxygen, carbon dioxide, the fresh culture fluid and the circular culture fluid can finish the gas-to-fluid and the fluid-to-fluid exchange and update inside the exchanger without opening the chamber, and the chamber is closed so as to ensure the pulse-typed circulation of the fresh culture fluid and the circular culture fluid and to support the biomimetic tissue cultivation in tissue engineering.

Description

technical field [0001] The invention relates to the field of biomedical engineering tissue cultivation, in particular to a culture liquid gas / liquid and liquid / liquid exchanger for bionic cultivation of tissue engineering tissue. Background technique [0002] The engineered cultivation of biological tissue needs to place the cultivated tissue in the culture fluid in the culture chamber of the engineered tissue culture system for cultivation, and the culture fluid provides the required nutrition for the cultivated tissue. Since the nutrients in the culture medium will be consumed after being used for a period of time, it is necessary to update the culture medium in the culture chamber, so that the fresh culture fluid can bring nutrients into the culture chamber, so that the culture fluid in the culture chamber can maintain sufficient Nutrients, which provide nourishment to cultured tissues. Usually, the replacement of the culture medium during the use of the existing enginee...

AI Technical Summary

Problems solved by technology

Usually, the replacement of the culture medium during the use of the existing engineered tissue culture system is to open the culture chamber to replace the fresh culture medium, that is, open the culture chamber to take out part of the used culture medium, and then inject fresh culture medium. The way of changing the culture medium is easy to destroy the steady state of the biochemical microenvironment in the culture process in the process of changing the culture medium every time, and lose some active factors secreted by the tissue with the culture medium taken out, which affects the effect of tissue culture; and this It is cumbersome to open the warehouse to replace the culture medium, which is easy to cause bacterial contamination and cause tissue culture failure

The technical scheme of "Cyclic and Physiological Stress Simulation Engineered Tissue Three-Dimensional Culture Device" with publication number CN1155690C provides a culture device for continuous perfusion to circulate the culture fluid. The bottle is connected to the culture room through a silicone tube to form a cycle. The new culture solution inlet of the circulating culture solution storage bottle is connected to the fresh culture solution storage bottle through a silicone tube. The culture room is connected to the waste liquid collection bottle through a silicone tube to make the circulation culture solution storage bottle The circulating culture solution in the medium is driven by the liquid flow drive device to form a circulation and discharge through the culture chamber, and the new culture solution in the fresh culture solution storage bottle is driven by the liquid flow drive device to replenish the fresh culture medium in the circulation culture solution storage bottle liquid, this kind of culture device can make the circulating culture liquid circulate through the culture room, avoiding the culture room to open the warehouse many times to replace the new culture liquid during the cultivation process, which is an improvement compared with the traditional culture device, but this fresh There is no circulation structure between the culture medium storage bottle and the circulating culture medium storage bottle, the fresh culture medium is just added and injected into the circulating culture medium storage bottle to mix with the circulating culture medium, and a certain amount of fresh culture medium should be injected into the circulating culture medium storage bottle Therefore, a certain amount of circulating culture solution must be discharged, which will cause the amount of fresh culture solution in the fresh culture solution storage bottle to decrease until it is used up, which can only meet the consumption of culture solution for a short period of time. For tissue engineering tissue culture, it is necessary to open the bottle to add fresh culture solution. Although the number of times to open the bottle to add fresh culture solution is reduced, it is an improvement compared with the traditional culture device, but there is still the possibility of contamination; and this device only completes the cycle The exchange of the amount of culture medium and fresh culture medium cannot form the exchange of nutrients between the circulating culture medium and the fresh culture medium, and the active factors secreted by the tissue during the tissue culture process will also be partially lost with the discharge of the culture medium. Reuse

At the same time, the circulating culture solution storage bottle of the device has a cavity structure, and the upper end of the circulating culture solution storage bottle is provided with an exhaust port to communicate with the outside atmosphere, and a silicone tube connected with the gas cylinder is connected to the upper end of the circulating culture solution storage bottle. Insert, the microporous gas injector provided at the end of the silicone tube is inserted into the culture solution in the circulating culture solution storage bottle, and the upper end of the fresh culture solution storage bottle is also provided with an exhaust port to communicate with the outside atmosphere, so that the circulation culture solution storage bottle There is no airtight space in the inner and fresh culture medium storage bottles, so the circulation drive of the circulating culture medium is only suitable for perfusion circulation using a peristaltic pump as the liquid flow drive device. If a pulse type telescopic pump is used, the circulating culture medium will be stored in the bottle The culture solution is ejected from the exhaust port under the driving pressure of the telescopic pump, so it cannot form a pulsating bionic cycle that simulates heart motion, and cannot constitute a true tissue engineering tissue bionic cultivation.

In view of the above reasons, there is currently no device in the field of tissue engineering tissue cultivation that can simultaneously simulate the gas exchange function of the lungs, the function of the kidneys to excrete metabolic waste, and the function of human nutrition supply, and it is still impossible to realize the bionics of material exchange in the true sense. Therefore, a device that is neither It is a device that can update the culture medium by opening the warehouse, and can also update the nutrient and gas components of the culture medium, so as to realize the bionic cultivation of tissue engineering tissues

[0003] Moreover, the current methods of gas-liquid exchange in the field of tissue engineering tissue cultivation mainly include: the upper end of the culture bottle is not sealed, and the air is in contact with the liquid surface of the culture liquid to form a natural exchange between the air and the culture liquid; A microporous gas injector is installed at the end of the tube, and oxygen is generated by injecting oxygen into the culture solution to generate air bubbles that contact the culture solution for oxygenation. The disadvantage of this method is that the bubbles will cause a large amount of foam on the liquid surface, which is easy to breed bacteria and cause contamination, resulting in tissue culture failure. There is also a semi-permeable membrane to seal the culture chamber mouth, the culture fluid fills the culture chamber, and the gas-liquid exchange is realized through the semi-permeable membrane. Although the chance of contamination caused by the gas-liquid exchange is reduced, the exchange efficiency is low and it is not suitable for tissue engineering. organize industrial production

Images