Electromagnetically driven rolling loading bioreactor

Abstract

The present invention discloses an electromagnetically driven rolling-type loaded bioreactor, comprising: a culture box, a culture fluid perfusion system, an electric excitation coil, a permanent magnet roller, a culture bed, a rack and a thin film pressure sensor; when working, the culture fluid perfusion system, the permanent magnet roller, the culture bed and the rack are located in the culture box, the oxygen content in the culture box is 1%-10%, and the temperature is 37 degrees. The culture fluid perfusion system is connected to the culture box through a silicone tube to control the circulation of the culture fluid in the culture box to ensure that the cartilage culture is in a biological environment where cells can grow. The electric excitation coil is energized in turn to attract the permanent magnet roller to generate torque, and the rack cooperates with the permanent magnet roller to generate torque on the culture fluid roller fixed on the culture bed. A rolling load is applied to the culture. There is an elastic silicone strip under the rack to provide floating support for the rack, simulating real ecological conditions. The incubator is in a fully enclosed state to avoid contamination. The rolling function of the cartilage culture is provided by a rolling permanent magnet roller. By changing the frequency and waveform of the excitation current of the electric excitation coil, various pressures are applied to the cartilage culture. The thin film pressure sensor outputs the pressure value on the culture in the form of an electrical signal in real time. It can also change the size of the excitation current to change the electromagnetic force exerted on the permanent magnet roller to apply different compression amounts to the cartilage culture, thereby completing the growth and development of cartilage cultures under different mechanical environments.

Description

Technical field:

[0001] The present invention relates to an electromagnetically driven rolling-type loaded bioreactor, in particular to a bioreactor which simulates the physical environment of joints under rolling load and hypoxic conditions and is applied to cell and tissue culture and preservation, and belongs to the technical field of biomedical engineering. Background technology:

[0002] Articular cartilage injury is one of the common surgical diseases, usually caused by trauma or chronic diseases such as osteoarthritis. The clinical manifestations are intractable rest pain accompanied by functional impairment. In severe cases, joint function may be completely lost, becoming one of the main causes of limb disability and loss of labor force. Cartilage tissue is the load-bearing structure of the human body and is sensitive to the mechanical environment. Abnormal mechanical environment can cause its degradation or degeneration. The physical environment where articular cartilage is located is a low-oxygen environment, and the mechanical environment is the most important factor affecting the survival of cartilage tissue.

[0003] Since cartilage tissue lacks blood vessels, nerves and lymphatic vessels, its regeneration capacity is extremely limited, while conservative drug treatment and total joint replacement have their own limitations. Using cytology and tissue engineering technology to construct functional cartilage tissue in vitro is an effective way to solve this problem.

[0004] The general method of constructing functional cartilage tissue in vitro with tissue engineering technology is to inoculate autologous or allogeneic cells into a degradable biomaterial scaffold, regulate cell growth through stimulation of different factors, and then implant the cell-biomaterial into the tissue defect site in the body to achieve the purpose of repairing tissue and organ defects. When the human body walks, the distal femur and proximal tibia of the knee joint contact each other, and there is a rolling effect, in which the articular cartilage is compressed and sheared. At the same time, the cartilage tissue is subjected to low-frequency and high-amplitude loads. Therefore, from the perspective of bionics, we propose to use rolling loads to simulate the mechanical conditions of the joint, and optimize the mechanical conditions of the cartilage culture by regulating frequency, pressure, and shear force.

[0005] At present, some scholars have used a method of applying mechanical loads to cultures by using electromechanical systems to cultivate cartilage tissue in vitro, and have made some progress. However, most existing bioreactors use a screw-type power source connected to the culture space, which is easy to cause contamination, leading to a large number of bacteria breeding during the culture process, interfering with the experimental results. In addition, due to the large mass of the mechanical transmission components, the reciprocating frequency of the roller is low. Using a dynamic magnetic field as a power source does not require a mechanical transmission structure, which can make the interior of the incubator completely closed, the culture is not easy to be contaminated, and the application reliability of the loading device is increased. In addition, through dynamic magnetic control, the frequency and amplitude range of the mechanical load loaded on the culture can be wider and the response speed can be faster. Therefore, it is necessary to invent an electromagnetically driven rolling loading bioreactor to ensure the sterile environment inside the bioreactor, control the interference variables of the experiment, and help further clarify the true situation of the response of human cartilage tissue to mechanical stimulation. Summary of the invention:

[0006] The purpose of the present invention is to provide an electromagnetically driven rolling loading bioreactor to solve the deficiencies in the prior art. The bioreactor is used to culture cartilage cultures by using electromagnetically driven rollers to apply rolling loads to the cultures, simulating the human articular cartilage environment in a hypoxic environment.

[0007] In order to achieve the above-mentioned purpose, the present invention provides an electromagnetically driven rolling loading bioreactor, comprising: a culture box, a culture fluid perfusion system, an electric excitation coil, a permanent magnet roller, a thin film pressure sensor, and a glass cover plate; when working, the electric excitation coil is energized in sequence to apply torque to the permanent magnet roller, so that the roller rolls back and forth on the culture bed under the limit cooperation of the rack, and an elastic silicone strip is provided under the rack to provide floating support for the rack, the oxygen content in the culture box is 1%-10%, the culture fluid perfusion system is connected to the culture box through a silicone tube, and the culture fluid replacement in the culture box is controlled to ensure that the cartilage culture is in a biological environment where cells can grow, and by adjusting the duty cycle and change frequency of the input current of the electric excitation coil, the permanent magnet roller applies rolling pressure on the culture bed with different pressures and frequencies to simulate the real ecological situation; the thin film pressure sensor is located under the culture bed, and the pressure value is output in the form of an electrical signal to realize dynamic adjustment of the pressure value; the culture box is in a closed state to avoid contamination; the glass cover plate is covered on the top of the culture box, which is convenient for observing the situation in the culture box;

[0008] The incubator is commonly used for biological cell culture, is made of polytetrafluoroethylene, can withstand moist heat sterilization, and can be customized on the market; the oxygen content in the incubator is achieved by adding 50%-95% CO2 into the incubator;

[0009] The cartilage culture is: chondrocytes, cartilage tissue, chondrocyte and scaffold complex or cartilage transplant tissue;

[0010] The permanent magnet roller is made of cylindrical polytetrafluoroethylene, and neodymium iron boron magnets are alternately inlaid on the side of the cylinder with N poles and S poles, and gears are inlaid on the top and bottom of the cylinder for matching with the rack;

[0011] The rack is installed in parallel inside the incubator and cooperates with the gear on the permanent magnet roller to constrain the movement of the roller;

[0012] The culture fluid perfusion system includes a culture fluid storage bottle, and a peristaltic pump provides flow power;

[0013] When working, the cartilage culture is fixed on the culture bed, the permanent magnet roller contacts the cartilage culture, the electric excitation coil is alternately energized to generate a magnetic field, and the permanent magnet roller is driven to roll and press on the culture bed to complete the cartilage culture rolling function;

[0014] By changing the excitation current of the electric excitation coil, a variety of rolling loads with different values ​​and frequencies can be provided;

[0015] The present invention is an electromagnetically driven rolling loading bioreactor, which has the advantages and functions of: the electromagnetically driven roller realizes the fully enclosed structure of the incubator, which is beneficial to ensure the sterile environment in the incubator; the use of rolling load and low oxygen environment is closer to the physiological conditions of joints. Description of the drawings:

[0016] Figure 1 is the overall block diagram of the bioreactor of the present invention;

[0017] Figure 2 A permanent magnet roller in the bioreactor of the present invention;

[0018] Figure 3 A culture box in the bioreactor of the present invention;

[0019] Figure 4 A schematic diagram of the working process of the bioreactor of the present invention; Specific implementation method:

[0020] In order to make the purpose, method of use and efficacy of the present invention more clearly understood, the present invention is further described in detail below in conjunction with examples and drawings. The exemplary embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention.

[0021] An electromagnetically driven roller-loading bioreactor, such as Figure 4The invention comprises: an incubator, a culture fluid perfusion system, an electric excitation coil, a permanent magnet roller, a culture bed, a rack and a thin film pressure sensor. When working, the culture fluid perfusion system, the permanent magnet roller, the culture bed and the rack are located in the incubator. The oxygen content in the incubator is 1%-10%, and the temperature is 37 degrees. The culture fluid perfusion system is connected to the incubator through a silicone tube to control the circulation of the culture fluid in the incubator to ensure that the cartilage culture is in a biological environment where cells can grow. The electric excitation coil is energized in turn to attract the permanent magnet roller to generate torque, and the rack cooperates with the permanent magnet roller to generate torque on the culture bed fixed on the culture bed. A rolling load is applied to the culture to simulate real ecological conditions; the incubator is in a fully enclosed state to avoid contamination. The rolling function of the cartilage culture is provided by the rolling permanent magnet roller. By changing the frequency and waveform of the excitation current of the electric excitation coil, various pressures are applied to the cartilage culture. The thin film pressure sensor outputs the pressure value on the culture in the form of an electrical signal in real time. It can also change the size of the excitation current to change the electromagnetic force exerted on the permanent magnet roller to apply different compression amounts to the cartilage culture, thereby completing the growth and development of the cartilage culture under different mechanical environments.

[0022] The incubator is commonly used for biological cell culture, is made of polytetrafluoroethylene, can withstand moist heat sterilization, and can be customized on the market; the oxygen content in the incubator is achieved by adding 50%-95% CO2 into the incubator;

[0023] The cartilage culture of the present invention is: chondrocytes, cartilage tissue, chondrocyte and scaffold complex or cartilage transplant tissue;

[0024] The culture fluid perfusion system of the present invention comprises a culture fluid storage bottle, and a peristaltic pump provides flow power;

[0025] The incubator of the present invention is as follows Figure 3 It includes a culture bed, a rack and a thin film pressure sensor; the rack is arranged on both sides of the culture bed; the thin film pressure sensor is arranged under the culture bed;

[0026] The surface of the permanent magnet roller is coated with a polytetrafluoroethylene film with a thickness of 0.5 mm to prevent relative sliding and adhesion from causing damage to the culture;

[0027] Fixing the cartilage culture by tying the cartilage culture to the culture bed with a silicone band;

[0028] When the bioreactor is working, 50%-95% CO2 is added to the incubator to achieve an indoor oxygen content of 1%-10%, and the temperature is adjusted to 37 degrees; the cartilage culture is fixed on the surface of the culture bed, and the permanent magnet roller is loaded with a magnetic field at a set frequency and speed by the electric excitation coil. The permanent magnet roller is driven by the electromagnetic force to perform reciprocating rolling motion. The permanent magnet roller fits the cartilage culture through electromagnetic force and gravity. The excitation current of the electric excitation coil can also be changed to change the magnitude of the electromagnetic force, so that the pressure of the permanent magnet roller on the culture bed changes, and the rolling loading function of the cartilage culture is realized; the glass cover is covered on the top of the incubator to keep the inside of the incubator in a sterile sealed environment; at the same time, the culture fluid perfusion system is connected to the incubator through a silicone tube to control the circulation of the culture fluid in the incubator to ensure that the cartilage culture is in a biological environment where cells can grow. In this way, the rolling load of the culture and the culture under hypoxic conditions are realized. After the experiment, the incubator and the permanent magnet roller of the reactor can be disassembled for easy cleaning and disinfection.

Claims

1. An electromagnetically driven rolling loading bioreactor, characterized in that: The bioreactor comprises an incubator, a culture fluid perfusion system, an electric excitation coil, a permanent magnet roller, a culture bed, a rack and a thin film pressure sensor. When working, the culture fluid perfusion system, the permanent magnet roller, the culture bed and the rack are located in the incubator, the oxygen content in the incubator is 1%-10%, and the temperature is 37 degrees. The culture fluid perfusion system is connected to the incubator through a silicone tube to control the circulation of the culture fluid in the incubator to ensure that the cartilage culture is in a biological environment where cells can grow. The electric excitation coil is energized in turn to attract the permanent magnet roller to generate torque, and the rack cooperates with the permanent magnet roller to generate torque on the culture bed fixed in the culture bed. The culture on the bed is subjected to rolling load to simulate the real ecological situation; the incubator is in a fully enclosed state to avoid contamination, and the rolling function of the cartilage culture is provided by the rolling permanent magnet roller. By changing the frequency and waveform of the excitation current of the electric excitation coil, various pressures are applied to the cartilage culture. The thin-film pressure sensor outputs the pressure value on the culture in the form of an electrical signal in real time, and can also change the magnitude of the excitation current to change the electromagnetic force exerted on the permanent magnet roller to apply different compression amounts to the cartilage culture, thereby completing the growth and development of the cartilage culture under different mechanical environments; The permanent magnet roller is a hollow cylindrical polytetrafluoroethylene material, and strip neodymium iron boron magnets are inlaid alternately with N poles and S poles in the cylindrical surface, and gears made of polytetrafluoroethylene are installed at both ends of the cylinder; The rack is made of polytetrafluoroethylene and is used to cooperate with the gear on the permanent magnet roller. An elastic silicone strip is supported under the rack. The elastic silicone strip of the permanent magnet roller is deformed under the action of magnetic force to adjust the distance between the permanent magnet roller and the culture bed. The culture is fixed on the culture bed, and the magnet roller changes the compression deformation of the culture. The rack cannot move horizontally, ensuring that there is no relative sliding between the roller and the culture bed. The cartilage culture is fixed on the culture bed, the permanent magnet roller is in contact with the cartilage culture, and the electric excitation coil can generate a magnetic field after being energized, attracting the magnet on the permanent magnet roller, generating an eccentric torque on the roller to make the roller move horizontally, and the pressure acting on the culture can be changed by changing the magnitude of the excitation current, and the frequency characteristics of the roller to the pressure acting on the culture bed can be changed by changing the energization frequency of the excitation coil, so as to achieve the application of various pressures on the cartilage culture; the electric excitation coil generates a magnetic field, and the permanent magnet roller rolls, completing the function of rolling the cartilage culture; The thin film pressure sensor can output the pressure exerted on the culture in the form of an electrical signal in real time. According to the output value of the electrical signal, the excitation current is adjusted, and the contact pressure of the permanent magnet roller on the cartilage culture is adjusted, so that the loading pressure on the culture can be dynamically controlled.

2. The electromagnetic driven roller loading bioreactor according to claim 1, characterized in that: The cartilage culture material is: chondrocytes, cartilage tissue, chondrocytes and scaffold complex or cartilage transplant tissue; the bioreactor is used for cartilage culture, including chondrocytes, cartilage tissue, chondrocytes and scaffold complex or cartilage transplant tissue.

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