Mechanical device for promoting maturation of cardiomyocytes and control method thereof

Abstract

The present specification relates to the field of biomedical engineering, and more particularly to a mechanical device for promoting maturation of cardiomyocytes and a control method thereof. The mechanical device uses a dynamic mechanical loading method based on the principle of mechanical pendulum to periodically stretch the culture medium of induced pluripotent stem cell-derived cardiomyocytes. The device structure mainly includes: a swing shaft for loading mechanical stimulation, a spring and gear set, a pendulum, a mass block; a traction rod for fixing and pulling cells, an elastic cell culture plate; device support, fixing, and adjusting components, etc. During operation, by adjusting the position of the mass block and the tension of the spring, the continuous and adjustable continuous swing of the pendulum is realized, the elastic cell culture plate is stretched through the traction rod, and the in-vivo mechanical environment is simulated. The maturation of iPSC-derived cardiomyocytes is promoted, the contractility and electrophysiological properties are improved, and the cardiomyocytes are closer to in-vivo mature cardiomyocytes.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering, and in particular to a mechanical device and control method for promoting the maturation of cardiomyocytes. Background Technology

[0002] Cardiac organoid research is a cutting-edge area in regenerative medicine, aiming to study cardiac development, disease mechanisms, and drug screening by mimicking the structure and function of cardiac tissue. In this field, cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs) have attracted significant attention due to their similarity to mature cardiomyocytes. However, iPSC-differentiated cardiomyocytes often lack sufficient mechanical stimulation during in vitro culture, limiting their transformation into mature cardiomyocytes and their functional performance. Therefore, developing a mechanical device that can effectively mimic the in vivo mechanical environment and promote the maturation of iPSCs into cardiomyocytes has significant scientific and clinical application value for cardiac organoid research.

[0003] Existing in vitro culture techniques generally cannot provide a mechanical environment similar to that in vivo, especially those that can simulate the dynamic mechanical conditions of the heart's periodic contraction and relaxation. Researchers have invented and reported various mechanical loading devices for cardiomyocyte culture, such as cell culture devices based on elastic membranes, magnetically controlled cell dynamic mechanical stimulation culture devices, and cell culture devices that apply mechanical stimulation by simulating vascular pulsation or fluid shear forces. Some studies have also attempted to provide stimulation signals to cardiomyocytes using electrical stimulation devices. While these devices can simulate mechanical stimulation to some extent, they often suffer from drawbacks such as complex operation, reliance on external power supplies, inconvenience in high-temperature and high-pressure sterilization, high costs for long-term culture maintenance, and an inability to accurately simulate the biomechanical environment, thus limiting the maturation and function of iPSC-differentiated cardiomyocytes.

[0004] There is an urgent need for a mechanically stimulated cell culture device to solve the problem of inconvenience in high-temperature and high-pressure sterilization due to reliance on external power supply in existing technologies. Summary of the Invention

[0005] To address the problems in the prior art, this specification provides a mechanical device and its control method for promoting cardiomyocyte maturation. Based on the principle of mechanical oscillation, it stimulates iPSC-derived cardiomyocytes and, by mimicking the mechanical environment in vivo, promotes the maturation and functional enhancement of iPSC-differentiated cardiomyocytes. This provides an innovative technical solution for research on cardiac organoids and cardiovascular diseases, solving many problems in the prior art, such as reliance on external power supply, inconvenience of high-temperature and high-pressure sterilization, high cost of long-term culture maintenance, and inability to accurately simulate the biomechanical environment.

[0006] To solve the above-mentioned technical problems, the specific technical solution in this specification is as follows:

[0007] This specification provides a mechanical device for promoting cardiomyocyte maturation, including a vertical support, a device base, a support rod, a rotating shaft, a pendulum, a traction rod, an elastic cell culture plate, and a spring and gear set;

[0008] The vertical bracket is vertically installed on one side of the device base, and a traction rod is connected to the middle of the vertical bracket and a support rod is connected to the top.

[0009] The support rod is connected to the rotating shaft and rotatably connected to the pendulum through the rotating shaft;

[0010] The rotating shaft is equipped with the mainspring and gear set, wherein the mainspring is made of an elastic component and has adjustable tension, and is used to provide driving force for the pendulum by rotating.

[0011] The gear set consists of gears of different sizes, which convert the rotational motion of the mainspring into the oscillating motion of the pendulum through the meshing of the gears;

[0012] The pendulum is connected to another traction rod at the horizontal height of the middle part of the vertical support;

[0013] The elastic cell culture plate is connected between the two traction rods and is used to place culture medium and cardiomyocytes. It is repeatedly stretched following the swinging motion of the pendulum.

[0014] Furthermore, the device also includes: multiple fixing screws,

[0015] The fixing screws are respectively sleeved on the top and middle of the vertical bracket, and are used to fix and connect the support rod and the traction rod on one side of the elastic cell culture plate;

[0016] The fixing screw is fitted onto the middle of the pendulum and is used to fix the traction rod on the other side of the elastic cell culture plate.

[0017] Furthermore, the device also includes: a scale, a mass block, a tray, and an adjusting nut;

[0018] The mass block is detachably mounted on the tray, which is fixed to the pendulum by an adjusting nut. The adjusting nut can move (or slide) along the axial direction of the pendulum via the thread of the pendulum.

[0019] The position of the tray is determined according to the scale, which is used to calibrate the height of the center of gravity of the pendulum.

[0020] Furthermore, the device also includes:

[0021] Adjusting the position of the mass block and the tension of the spring allows the pendulum to oscillate continuously with an adjustable period.

[0022] The elastic cell culture plate is stretched by the traction rod to simulate the in vivo mechanical environment during the maturation process of cardiomyocytes.

[0023] Furthermore, the device also includes:

[0024] The traction rod is made of stainless steel and is T-shaped. The horizontal beam is embedded in the edge pre-drilled hole of the elastic cell culture plate and is the same width as the elastic cell culture plate.

[0025] The other end of the traction rod is connected to a fixing screw on the pendulum or vertical support.

[0026] Furthermore, the device also includes:

[0027] The elastic cell culture plate is made of silicone rubber, which is elastic, and has a through hole of the same size reserved for placing the traction rod;

[0028] The elastic cell culture plate has one or more reservoir arrays for cell culture.

[0029] This specification also provides a method for controlling a mechanical device that promotes cardiomyocyte maturation, the method comprising:

[0030] Cell culture medium was placed on the elastic cell culture plate, and iPSC-derived cardiomyocytes were inoculated.

[0031] The elastic cell culture plate is continuously stretched by the two traction rods to stimulate the iPSC-derived cardiomyocytes, simulating the in vivo mechanical environment.

[0032] Furthermore, the continuous stretching of the elastic cell culture plate by the two aforementioned traction rods further includes,

[0033] The elastic cell culture plate is periodically stretched through the coordinated action of the support rod, the rotating shaft, and the pendulum.

[0034] The oscillation cycle is adjusted by regulating the position of the mass block and the tension of the spring according to the cardiomyocytes, thereby stimulating the iPSC-derived cardiomyocytes in a simulated in vivo mechanical environment.

[0035] The mechanical device for promoting cardiomyocyte maturation according to embodiments of this specification includes a vertical support, a device base, a support rod, a rotating shaft, a pendulum, a traction rod, an elastic cell culture plate, and a spring and gear set. The vertical support is vertically mounted on one side of the device base, with a traction rod connected to the middle and a support rod connected to the top. The support rod is connected to the rotating shaft and rotatably connected to the pendulum. A spring and gear set are installed in the rotating shaft. The spring is made of an elastic component with adjustable tension, used to provide driving force for the pendulum's rotational motion. The gear set consists of gears of different sizes, which convert the rotational motion of the spring into the pendulum's oscillating motion through gear meshing. Another traction rod is connected at a horizontal level between the pendulum and the middle of the vertical support. The elastic cell culture plate is connected between the two traction rods and is used to hold culture medium and cardiomyocytes, which are repeatedly stretched following the pendulum's oscillating motion. Through the above technical solution, the mechanical device of this invention can effectively promote the maturation of iPSC-derived cardiomyocytes, improve their contractility and electrophysiological characteristics, making them closer to mature cardiomyocytes in vivo, providing a new technical means for the research of cardiac organoids and the treatment of cardiovascular diseases. Attached Figure Description

[0036] To more clearly illustrate the technical solutions in the embodiments or prior art of this specification, the drawings used in the description of the embodiments or prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this specification. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0037] Figure 1 The diagram shown is a schematic representation of the overall structure of a mechanical device for promoting cardiomyocyte maturation in an embodiment of this specification.

[0038] Figure 2 The diagram shown is a flowchart illustrating a mechanical method for promoting cardiomyocyte maturation in an embodiment of this specification.

[0039] Figure 3 The diagram shown is a flowchart illustrating a mechanical method for promoting cardiomyocyte maturation in another embodiment of this specification.

[0040] [Explanation of Figure Markers]:

[0041] 1. Vertical support;

[0042] 2. Fixing screws;

[0043] 3. Device base;

[0044] 4. Support rod;

[0045] 5. Rotation axis;

[0046] 6. Mainspring and gear set;

[0047] 7. Pendulum;

[0048] 8. Scale;

[0049] 9. Mass block;

[0050] 10. Pallet;

[0051] 11. Adjusting nut;

[0052] 12. Towing bar;

[0053] 13. Elastic cell culture plate;

[0054] 14. Culture medium and cardiomyocytes. Detailed Implementation

[0055] The technical solutions in the embodiments of this specification will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this specification, and not all embodiments. Based on the embodiments in this specification, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this specification.

[0056] It should be noted that the terms "first," "second," etc., in the specification, claims, and accompanying drawings are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such data can be interchanged where appropriate so that the embodiments described herein can be implemented in orders other than those illustrated or described herein. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion; for example, an apparatus, product, or device comprising a series of units is not necessarily limited to those explicitly listed, but may include other units not explicitly listed or inherent to such products or devices.

[0057] Furthermore, for ease of description, some embodiments of this specification may use spatially relative terms such as "above," "below," "top," and "under" to describe the relationship between one element or component and another element or component as shown in the accompanying drawings of the embodiments. It should be understood that, in addition to the orientations described in the drawings, the spatially relative terms are also intended to include different orientations of the device during use or operation. For example, if the device in the drawings is flipped over, an element or component described as "below" or "under" other elements or components will subsequently be positioned "above" or "on top" other elements or components.

[0058] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0059] To address the problems existing in the prior art, this specification provides a mechanical device and its control method for promoting the maturation of cardiomyocytes. Figure 1 The diagram shown is an overall structural schematic of a mechanical device for promoting cardiomyocyte maturation according to an embodiment of this specification. The basic structure of the mechanical device for promoting cardiomyocyte maturation is illustrated in this figure; however, it may include more or fewer units or components based on conventional or non-inventive methods. The units or modules listed in the embodiment are merely functionally categorized units or components. In actual system or device product implementation, the units and components can be adjusted.

[0060] In the embodiments described in this specification, the mechanical stimulation pattern during the contraction and relaxation of the heart is non-uniform and non-uniform acceleration, which is the key to the device's ability to better simulate this process.

[0061] First: Nonlinear Dynamic Behavior of the Heart: The contraction and relaxation of the heart is a complex biomechanical process involving the nonlinear mechanical properties of the myocardium. Studies have shown that the mechanical behavior of the heart is not a simple uniform motion, but rather exhibits acceleration and deceleration characteristics, especially at different stages of each heartbeat cycle, where mechanical loads and velocities change significantly. The contraction of the cardiac muscle often displays an acceleration-deceleration dynamic pattern, and this mechanical pendulum device can precisely simulate this process. Second: The Effects of Mechanical Stimulation on Cardiomyocytes: Many studies have demonstrated that periodic mechanical stimulation helps promote the development and maturation of cardiomyocytes. Mechanical stimulation not only enhances cell synchronicity but also improves cell contractility and the stability of spontaneous beating. Research has reported that biomechanical stimulation, through the application of periodic stretching or pulling, can improve cardiomyocyte function, promote their structural and functional maturation, and help simulate the natural contraction and relaxation environment of the heart in vivo, with variations in frequency and amplitude having different effects on cell development. Third: Basis for Non-Uniform Mechanical Stimulation: Research by the Bursac group at Duke University has shown that non-uniform stretching patterns better simulate the behavior of the heart under physiological conditions compared to uniform stretching. The experiment used various stretching patterns with different frequencies and amplitudes to simulate cardiac contraction and relaxation under physiological conditions. Compared with the static stretching group and the uniform stretching group, the dynamic stretching group showed stronger cell synchronization and higher contractile force. Since cardiac contraction and relaxation are non-uniform, the mechanical stimulus should reflect this characteristic to more realistically simulate the physiological environment.

[0062] In one embodiment of this specification, in order to address the shortcomings of existing technologies that use electrical stimulation devices to provide stimulation signals to cardiomyocytes, such as reliance on external power supply, inconvenience of high-temperature and high-pressure sterilization, high cost of long-term culture maintenance, and inability to accurately simulate the biomechanical environment, which limit the maturity and function of iPSC differentiated cardiomyocytes, this embodiment of the specification provides a mechanical device to promote cardiomyocyte maturation, including a vertical support 1, a device base 3, a support rod 4, a rotating shaft 5, a pendulum 7, a traction rod 12, an elastic cell culture plate 13, and a spring and gear set 6;

[0063] The vertical bracket 1 is vertically installed on one side of the device base 3. The vertical bracket 1 is connected to a traction rod 12 in the middle and a support rod 4 at the top.

[0064] The support rod 4 is connected to the rotating shaft 5 and is rotatably connected to the pendulum 7 via the rotating shaft 5;

[0065] The rotating shaft 5 is equipped with the mainspring and gear set 6, wherein the mainspring is made of an elastic component and has adjustable tension, and is used to provide driving force for the pendulum 7 by performing rotational motion;

[0066] The gear set consists of gears of different sizes, which convert the rotational motion of the mainspring into the oscillating motion of the pendulum 7 through the meshing of the gears;

[0067] The pendulum 7 is connected to another traction rod 12 at the horizontal height of the middle part of the vertical support 1;

[0068] The elastic cell culture plate 13 is connected between the two traction rods 12 and is used to place culture medium and cardiomyocytes. It is repeatedly stretched following the swinging motion of the pendulum 7.

[0069] The mechanical device for promoting cardiomyocyte maturation according to embodiments of this specification includes a vertical support, a device base, a support rod, a rotating shaft, a pendulum, a traction rod, an elastic cell culture plate, and a spring and gear set. The vertical support is vertically mounted on one side of the device base, with a traction rod connected to the middle and a support rod connected to the top. The support rod is connected to the rotating shaft and rotatably connected to the pendulum. A spring and gear set are installed in the rotating shaft. The spring is made of an elastic component with adjustable tension, used to provide driving force for the pendulum's rotational motion. The gear set consists of gears of different sizes, which convert the rotational motion of the spring into the oscillating motion of the pendulum through gear meshing. Another traction rod is connected at a horizontal level between the pendulum and the middle of the vertical support. The elastic cell culture plate is connected between the two traction rods and is used to hold culture medium and cardiomyocytes, repeatedly stretching with the oscillating motion of the pendulum. Stretching the elastic cell culture plate by the traction rod simulates the in vivo mechanical environment during the cardiomyocyte maturation process. Through the above technical solutions, the mechanical device of the present invention can effectively promote the maturation of iPSC-derived cardiomyocytes, improve their contractility and electrophysiological properties, and make them closer to mature cardiomyocytes in vivo, providing a new technical means for the research of cardiac organoids and the treatment of cardiovascular diseases.

[0070] In one embodiment of this specification, the device further includes: a plurality of fixing screws 2.

[0071] The fixing screws 2 are respectively sleeved on the top and middle of the vertical bracket 1, and are used to fix and connect the support rod 4 and the traction rod 12 on one side of the elastic cell culture plate 13;

[0072] The fixing screw 2 is sleeved on the middle of the pendulum 7 and is used to fix the traction rod 12 on the other side of the elastic cell culture plate 13.

[0073] In another embodiment of this specification, the device further includes: a scale 8, a mass block 9, a tray 10, and an adjusting nut 11;

[0074] The mass block 9 is detachably mounted on the tray 10, and the tray 10 is fixed to the pendulum 7 by an adjusting nut 11. The adjusting nut 11 can move or slide along the axial direction of the pendulum 7 through the thread of the pendulum 7.

[0075] The position of the tray 10 is determined according to the scale 8, which is used to mark the height of the center of gravity of the pendulum 7.

[0076] In another embodiment of this specification, the device further includes: adjusting the position of the mass block 9 and the tension of the mainspring to make the pendulum swing continuously with an adjustable period;

[0077] The elastic cell culture plate is stretched by the traction rod 12 to simulate the in vivo mechanical environment during the maturation process of cardiomyocytes.

[0078] Meanwhile, the traction rod 12 is made of stainless steel and is T-shaped. The horizontal beam part is embedded in the edge reserved hole of the elastic cell culture plate 13 and is the same width as the elastic cell culture plate 13.

[0079] The other end of the traction rod 12 is connected to the fixing screw 2 on the pendulum 7 or the vertical support 1.

[0080] The elastic cell culture plate 13 is made of silicone rubber material, which is elastic, and has a through hole of the same size for placing the traction rod 12.

[0081] The elastic cell culture plate 13 has one or more reservoir arrays for cell culture.

[0082] Specifically, in one embodiment of this specification, the pendulum shaft is made of stainless steel with a diameter of 5-20mm, and is resistant to high-temperature and high-pressure sterilization to ensure smooth rotation. The mainspring is made of spring steel and has adjustable tension. The gear set consists of gears of different sizes, which, through meshing, convert the rotational motion of the mainspring into the oscillating motion of the pendulum. The pendulum is made of aluminum alloy or stainless steel, with a diameter of 10mm and a length of 200mm, and is connected to the mainspring and gear set at the pendulum shaft. The mass is made of cast iron or stainless steel, with a diameter of 60mm and a mass ranging from 100g to 1000g, and is mounted on the pendulum. It can slide along the pendulum axis to adjust the center of gravity of the pendulum. The pendulum has a scale with a length of 50mm and a scale interval of 1mm, used to mark the height position of the mass for precise adjustment. A tray is used to hold the mass and ensure its stability. The adjusting nut is located at the bottom of the pendulum and is fixed using the threads on the bottom of the pendulum. The position of the mass block and tray is adjusted and fixed by rotating the adjusting nut up and down. The traction rod is made of stainless steel and is T-shaped. The horizontal beam is embedded in a pre-drilled hole at the edge of the elastic cell culture plate, and is the same width as the cell culture plate. The vertical structure is 50mm long, and the other end is connected to the fixing screw on the pendulum or support. The elastic cell culture plate is made of silicone rubber, is elastic, and has a pre-drilled through hole of the same size for placing the traction rod, allowing it to deform under the tension of the traction rod. The cell culture plate is typically 80mm × 100mm in size and contains one or more reservoir arrays for cell culture. The reservoir width is 5–50mm. The system includes a vertical support, fixing screws, a base, and support rods, used to fix the entire device and allow the user to adjust the device to suit different experimental needs. Utilizing a mechanical pendulum principle reduces dependence on external power, facilitates sterilization, and allows placement within a cell culture incubator. Compared to technologies such as electric actuators, mechanical pendulums are better able to simulate the dynamic mechanical conditions and motion patterns of the periodic contraction and relaxation of the heart in vivo, thereby achieving dynamic mechanical stimulation of iPSC-derived cardiomyocytes by the in vivo mechanical environment. Furthermore, the periodic motion of the device can directly provide feedback on the contractile force of cardiomyocytes during the culture and maturation process, potentially leading to better culture results.

[0083] In the embodiments of this specification, in order to promote the maturation of cardiomyocytes, such as Figure 2 As shown, the control method steps of the mechanical device for promoting cardiomyocyte maturation include:

[0084] Step 201: Place cell culture medium on the elastic cell culture plate 13 and inoculate iPSC-derived cardiomyocytes;

[0085] Step 202: The elastic cell culture plate 13 is continuously stretched by the two traction rods 12 to stimulate the iPSC-derived cardiomyocytes in an in vivo mechanical environment.

[0086] Step 203: The elastic cell culture plate 13 is periodically stretched by the coordinated action of the support rod 4, the rotating shaft 5, and the pendulum 7.

[0087] Step 204: Adjust the position of the mass block and the tension of the spring according to the cardiomyocytes to regulate the oscillation period, stimulating the iPSC-derived cardiomyocytes in the presence of the in vivo mechanical environment.

[0088] Exemplarily, the specific steps of the control method for a mechanical device that promotes cardiomyocyte maturation, such as... Figure 3 As shown, it includes:

[0089] Step 301: Sterilize all operating devices at high temperature;

[0090] Step 302: Prepare cell culture medium and inoculate iPSC-derived cardiomyocytes onto an elastic cell culture plate fixed to the mechanical device;

[0091] Step 303: Through the synergistic action of the pendulum shaft, spring and gear set, pendulum, and mass block of the device, the periodic stretching of the cell culture substrate is achieved;

[0092] Step 304: Adjust the position of the mass block and the tension of the spring to adjust the oscillation period and maintain continuous oscillation;

[0093] Step 305: The elastic cell culture plate is stretched by a continuous traction rod to simulate the in vivo mechanical environment on iPSC-derived cardiomyocytes, maintaining appropriate mechanical stimulation conditions until the cardiomyocytes exhibit contractility and electrophysiological properties similar to those of mature cardiomyocytes in vivo.

[0094] For example, the device is first sterilized: the entire mechanical device assembly is placed in an autoclave and sterilized at 121°C for 20 minutes to ensure sterility. Then, the cell culture medium is prepared: iPSC-differentiated cardiomyocytes are inoculated into the reservoir of the elastic cell culture plate. The cell culture medium should contain nutrients necessary for cardiomyocyte differentiation and maturation, such as 10% fetal bovine serum and 1% penicillin / streptomycin. Next, the device is assembled: the pendulum shaft, mainspring and gear set, pendulum bob, mass, traction rod, and elastic cell culture plate are assembled according to the design requirements. The device is then fixed in the cell culture chamber to ensure stability. Then, mechanical stimulation is applied: by adjusting the tension of the mainspring and the position of the mass, the pendulum begins to swing, and the traction rod stretches the elastic cell culture plate, applying periodic mechanical stimulation to the iPSC-differentiated cardiomyocytes. The swing period of the pendulum can be adjusted by changing the position of the mass, with a range of 1 to 10 seconds. Finally, the oscillation period was adjusted: Based on the needs of cell culture, the oscillation period of the pendulum was adjusted by regulating the position of the mass and the tension of the spring to simulate different in vivo mechanical environments. For example, to simulate the systolic and diastolic phases of the heart, the oscillation period could be set to 1 second for systole and 2 seconds for diastole. After completing the device debugging, cell culture was observed: Under mechanical stimulation, the growth of iPSC-differentiated cardiomyocytes was observed regularly, and cell morphological changes, contractility, and electrophysiological characteristics were recorded. The observation period was once daily for 14 consecutive days. Finally, data analysis was performed to evaluate the effect of mechanical stimulation on cell maturation by comparing the characteristics of iPSC-differentiated cardiomyocytes before and after mechanical stimulation. The analysis included the measurement of cell contractility, the recording of electrophysiological characteristics using a microelectrode array system, and the detection of cardiomyocyte-specific marker expression using immunofluorescence staining.

[0095] In existing technologies, electric devices are typically driven by electric motors and transmission systems, and this motion is generally linear or uniform. However, the mechanical pendulum principle can provide non-uniform and non-uniform acceleration motion, which more closely approximates the dynamic characteristics of the heart's natural contraction and relaxation. The heart's contraction and relaxation exhibit significant non-linear characteristics, especially at different stages of each cycle, where the pattern of mechanical stimulation also changes significantly. Furthermore, the mechanical device can directly respond to the contractile force of cardiomyocytes during cell culture and maturation; this interactive driving method is something that traditional electric motor drives cannot achieve.

[0096] The device described in this specification does not rely on complex electrical components such as motors, electronic control systems, and power supplies. It utilizes mechanical oscillation and a spring to provide mechanical stimulation, thus reducing the complexity, cost, and compatibility of the equipment. Especially considering that the device needs to be placed entirely within a cell culture environment for extended periods, the mechanical structure, devoid of electrical components, can be sterilized entirely under high temperature and pressure. Furthermore, by adjusting the position of the mass and the tension of the spring, the device can precisely control the period, amplitude, and frequency of the pendulum, achieving continuous mechanical loading. This adjustment method is intuitive and simple, requires no complex electronic adjustment mechanisms, and generates almost no additional heat during long-term use.

[0097] It should also be understood that, in the embodiments of this specification, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this document generally indicates that the preceding and following related objects have an "or" relationship.

[0098] It should also be noted that the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that an apparatus or device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such an apparatus or device. Without further limitation, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the apparatus or device that includes said element.

[0099] This specification uses specific embodiments to illustrate the principles and implementation methods of this specification. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this specification. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the ideas of this specification. Therefore, the content of this specification should not be construed as a limitation of this specification.

Claims

1. A mechanical device for promoting cardiomyocyte maturation, characterized in that, It includes a vertical support (1), a device base (3), a support rod (4), a rotating shaft (5), a pendulum (7), a traction rod (12), an elastic cell culture plate (13), and a spring and gear set (6); The vertical bracket (1) is vertically installed on one side of the device base (3). A traction rod (12) is connected in the middle of the vertical bracket (1), and a support rod (4) is connected at the top. The support rod (4) is connected to the rotating shaft (5) and is rotatably connected to the pendulum (7) through the rotating shaft (5); The rotating shaft (5) is equipped with the spring and gear set (6), wherein the spring is made of an elastic component and has adjustable tension, and is used to perform rotational motion to provide driving force for the pendulum (7); The gear set is composed of gears of different sizes, and the rotational motion of the mainspring is converted into the swinging motion of the pendulum (7) through the meshing of the gears; The pendulum (7) is connected to another traction rod (12) at the horizontal height of the middle part of the vertical support (1); The elastic cell culture plate (13) is connected between the two traction rods (12) for placing culture medium and cardiomyocytes, and is repeatedly stretched following the swinging motion of the pendulum (7).

2. The mechanical device for promoting cardiomyocyte maturation according to claim 1, characterized in that, The device also includes: a plurality of fixing screws (2), The fixing screws (2) are respectively sleeved on the top and middle of the vertical bracket (1) for fixing the support rod (4) and the traction rod (12) on one side of the elastic cell culture plate (13); The fixing screw (2) is sleeved on the middle of the pendulum (7) and is used to fix the traction rod (12) on the other side of the elastic cell culture plate (13).

3. The mechanical device for promoting cardiomyocyte maturation according to claim 2, characterized in that, The device also includes: a scale (8), a mass block (9), a tray (10), and an adjusting nut (11); The mass block (9) is detachably mounted on the tray (10), which is fixed to the pendulum (7) by an adjusting nut (11). The adjusting nut (11) can move (or slide) along the axial direction of the pendulum (7) through the thread of the pendulum (7). The position of the tray (10) is determined according to the scale (8) to mark the height of the center of gravity of the pendulum (7).

4. The mechanical device for promoting cardiomyocyte maturation according to claim 3, characterized in that, The device further includes: Adjust the position of the mass block (9) and the tension of the spring to make the pendulum swing continuously with an adjustable period; The elastic cell culture plate is stretched by the traction rod (12) to simulate the in vivo mechanical environment during the maturation process of cardiomyocytes.

5. The mechanical device for promoting cardiomyocyte maturation according to claim 4, characterized in that, The device further includes: The traction rod (12) is made of stainless steel and is T-shaped. The horizontal beam part is embedded in the edge reserved hole of the elastic cell culture plate (13) and is the same width as the elastic cell culture plate (13). The other end of the traction rod (12) is connected to the fixing screw (2) on the pendulum (7) or the vertical bracket (1).

6. The mechanical device for promoting cardiomyocyte maturation according to claim 4, characterized in that, The device further includes: The elastic cell culture plate (13) is made of silicone rubber material, which is elastic and has a through hole of the same size for placing the traction rod (12); The elastic cell culture plate (13) has one or more reservoir arrays for cell culture.

7. A control method for a mechanical device that promotes cardiomyocyte maturation, characterized in that, The method of the control device for the mechanical device for promoting cardiomyocyte maturation as described in any one of claims 1-6 includes: Cell culture medium was placed on the elastic cell culture plate (13), and iPSC-derived cardiomyocytes were inoculated. The elastic cell culture plate (13) is continuously stretched by the two traction rods (12) to stimulate the iPSC-derived cardiomyocytes in a simulated in vivo mechanical environment.

8. The control method for the mechanical device for promoting cardiomyocyte maturation according to claim 7, characterized in that, The elastic cell culture plate (13) is further included by continuously stretching the two traction rods (12). The elastic cell culture plate (13) is periodically stretched by the coordinated action of the support rod (4), the rotating shaft (5), and the pendulum (7); The oscillation cycle is adjusted by regulating the position of the mass block and the tension of the spring according to the cardiomyocytes, thereby stimulating the iPSC-derived cardiomyocytes in a simulated in vivo mechanical environment.

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