Muscle tissue electro-mechanical co-stimulation system inspired by human muscle training

Abstract

The utility model provides a muscle tissue electricity-force co-stimulation system inspired by human muscle training. A uniform periodic electric field is generated through multiple electrodes which are annularly distributed to stimulate muscle tissues to contract, and meanwhile, the inherent elasticity of a spring structure provides a load for engineering skeletal muscle tissues, so that dynamic mechanical stimulation is provided. According to the utility model, electrical stimulation and dynamic mechanical stimulation of engineering skeletal muscle tissues can be realized at the same time.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of biomedical engineering, specifically a system can carry out electrical stimulation and dynamic mechanical stimulation to engineering skeletal muscle tissue. BACKGROUND

[0002] Skeletal muscle is one of the most important movement units of the human body. There are more than 600 skeletal muscles in the human body, which cooperatively drive the human body to complete complex and delicate movements. In addition, skeletal muscle plays an important role in maintaining body temperature and metabolic balance. With the rapid development of science and technology, researchers have carried out research on the reconstruction of skeletal muscle tissue in vitro. This research has important practical significance in many fields. For example, skeletal muscle physiology, skeletal muscle disease modeling, drug development and testing, and biological hybrid robots. However, due to the very complex multi-level structure of human skeletal muscle and the lack of relevant in vitro research methods, the current skeletal muscle tissue is facing the problem of low differentiation rate in vitro.

[0003] In order to promote the growth and differentiation of muscle cells and improve the maturity of engineering skeletal muscle tissue, researchers have carried out a number of studies. Related results show that mechanical stretching stimulation can promote the directional arrangement of cytoskeleton, protein synthesis and muscle cell hypertrophy in muscle tissue. On the other hand, electrical pulse stimulation is necessary for the normal growth and maturation of new fibers. Proper electrical stimulation helps myoblasts transform into contractile muscle tubes, thereby improving the differentiation efficiency and driving force of in vitro skeletal muscle tissue.

[0004] Although existing technologies have proposed some in vitro skeletal muscle tissue culture systems based on electrical or mechanical stimulation, they cannot effectively simulate the culture environment of human muscle tissue, so the differentiation degree of current engineering skeletal muscle tissue is still much lower than that of natural skeletal muscle tissue. In the human body, from embryo to adulthood, skeletal muscle tissue is always stimulated by a combination of nerve electrical stimulation and dynamic mechanical stimulation, and its performance is improved or maintained. Therefore, there is an urgent need for a new system that can co-stimulate in vitro skeletal muscle tissue, which helps to further improve the performance of in vitro skeletal muscle tissue. UTILITY MODEL CONTENT

[0005] In view of the problem that the current stimulation method is single and the effect is poor, the purpose of the utility model is to provide an electrical-force co-stimulation system for performance enhancement of engineering skeletal muscle tissue, which generates a periodic electric field through a ring-shaped distribution of multiple electrodes, so that the muscle tissue contracts, and dynamic mechanical stimulation is provided through a spring, thereby promoting the differentiation of myoblasts and improving the maturity and contraction force of muscle tissue.

[0006] The present application relates to an electrical-force co-stimulation system for performance enhancement of engineering skeletal muscle tissue and a control method thereof, which can simultaneously perform electrical and dynamic mechanical co-stimulation on engineering skeletal muscle tissue and real-time centripetal contraction force measurement.

[0007] The utility model discloses a following technical scheme realizes: the muscle tissue electric - force co - stimulation system inspired by human muscle training, comprising:

[0008] Electrode, annular distribution is in the culture dish edge, is connected with multichannel electric stimulator, is used for through the periodic electric pulse signal of multichannel electric stimulator, produces the periodic electric pulse stimulation of acting on muscle tissue;

[0009] Spring, movable end is connected with muscle tissue in culture dish, and fixed end is connected with servo electric jar through connecting piece, is used for acting on muscle tissue and producing dynamic mechanical stimulation;

[0010] Servo electric jar is connected with host computer through controller, is used for realizing the telescopic control of servo electric jar to drive spring movement according to the instruction of host computer.

[0011] The electrode is platinum sheet that 15mm long, 5mm wide, 0.1mm thick, and the electrode is multiple and evenly distributed.

[0012] The spring adopts PDMS elastic material, and the spring number of turns is 3 turns, the spring pitch is 1.5mm, the spring wire width is 0.8mm, the spring wire thickness is 0.5mm, and the spring elastic coefficient is 2.1mN / mm.

[0013] One end of the muscle tissue is connected with the movable end of the spring, and the other end is connected with the microcolumn fixed on the surface of the culture dish.

[0014] The system also includes a visual monitoring system, which is arranged directly above the culture dish.

[0015] The utility model has the following beneficial effects and advantages:

[0016] 1. The electric - force co - stimulation system for engineering skeletal muscle tissue performance enhancement, through the periodic electric field stimulation of the periodicity electric field stimulation of the annular distribution multiple electrode, muscle tissue contracts, and the inherent elasticity of spring is used to provide dynamic mechanical stimulation, so that the spring can monitor the change of muscle tissue contraction force in real time, and the position of the movable end of the spring is adjusted dynamically using the micro servo electric jar, so that the muscle tissue is provided with dynamic variable load. When the muscle tissue is stimulated by electricity, it contracts and drives the spring end to move by overcoming the spring resistance. In this process, the muscle tissue is stimulated by electricity and dynamic mechanical stimulation at the same time, and the differentiation efficiency and driving performance are significantly improved.

[0017] 2. The utility model does not need complex mechanical system and control method, and the inherent elasticity of spring can automatically realize the dynamic mechanical stimulation of muscle tissue after electric stimulation. The muscle tissue stimulation training process can be simplified, and the spring structure can also be used for online real-time detection of muscle tissue contraction force, without additional contraction force characterization means. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The system structure principle schematic view of the utility model.

[0019] Figure 2 The utility model muscle tissue and spring part's enlarged schematic view.

[0020] The meaning of each mark in the drawing is: 1 - micro servo electric cylinder;2 - connecting piece;3 - annular distribution multi-electrode;4 - PDMS spring structure;5 - engineering skeletal muscle tissue;6 - standard culture dish with 100mm diameter. DETAILED DESCRIPTION

[0021] The utility model will make further detailed description in combination with the drawings and examples.

[0022] The utility model is inspired by human skeletal muscle training mode, provide a kind of for engineering skeletal muscle tissue performance enhancement electric-power co-stimulation system.By annular distribution multi-electrode, generate uniform periodic electric field to stimulate muscle tissue contraction, while the inherent elasticity of spring structure provides load for engineering skeletal muscle tissue, to provide dynamic mechanical stimulation further, and using known spring coefficient of elasticity can also monitor the centripetal contraction dynamics of engineering skeletal muscle tissue in real time.By micro servo electric cylinder dynamic adjustment spring end position, to adjust engineering skeletal muscle tissue length, to provide variable load in the muscle tissue growth and development process, simulate the skeletal elongation in the growth process of human skeletal muscle.The utility model can realize electric stimulation and dynamic mechanical stimulation to engineering skeletal muscle tissue simultaneously, and can monitor its centripetal contraction force in real time, and dynamically adjust the mechanical load applied to muscle tissue.

[0023] As Figure 1 , Figure 2 As shown in the utility model first provides a kind of for engineering skeletal muscle tissue electric-power co-stimulation system, including: annular distribution multi-electrode, micro servo electric cylinder and PDMS spring;

[0024] The annular distribution multi-electrode is adhered to the edge of standard culture dish by biocompatibility glue, and is connected with multi-channel electric stimulator;The annular distribution multi-electrode is 8 metal platinum pieces with 15mm length, 5mm width and 0.1mm thickness;

[0025] The micro servo electric cylinder is fixed on system base using bolt, and the telescopic rod of electric cylinder is connected with connecting piece, and micro servo electric cylinder is controlled by USB controller by upper computer Matlab program;Connecting piece is connecting rod, so that the movement direction axis of electric cylinder is parallel with the telescopic direction axis of spring;Spring is connected with muscle tissue by anchoring etc. connecting mode.

[0026] The spring structure is adhered to the matching mechanism at one end by using a biocompatible glue, and is connected to a micro servo cylinder; the spring material is PDMS elastic material, the number of turns of the spring is 3 turns, the spring pitch is 1.5 mm, the spring wire width is 0.8 mm, the spring wire thickness is 0.5 mm, and the spring elastic coefficient is 2.1 mN / mm;

[0027] The working principle of the utility model comprises the following steps:

[0028] The matrix glue, collagen solution, NaOH solution, mouse C2C12 myoblast cells and cell growth culture medium are fully mixed and injected into the muscle tissue culture mold in advance;

[0029] Two days before the muscle tissue is formed, the culture solution is the growth culture medium, under the action of the cell traction force, the matrix is compacted, the muscle tissue volume is reduced, and a stable state is reached; after being cultured in the growth culture medium for two days, the growth culture medium is replaced by the differentiation culture medium; on the third day of the differentiation culture medium culture, the muscle tissue produces a spontaneous contraction phenomenon; on the fifth day, the muscle tissue is transferred into the electric-force co-stimulation system, one end is connected to the spring movable end, and the other end is connected to the micro column on the surface of the culture dish;

[0030] The position of the spring movable end is adjusted by the micro servo cylinder, and the muscle tissue length is kept as the original length;

[0031] The electric-force co-stimulation specifically comprises the following steps:

[0032] A periodic electric field is generated by the electrode through the multi-channel electric stimulator by using software and electric stimulation programs;

[0033] The electric stimulation frequency is 1 Hz, the electric field intensity is 1.5 V / cm, the pulse width is 6 ms, the stimulation time is 7.5 minutes per hour, the rest time is 52.5 minutes per hour, and the co-stimulation time is three days.

[0034] The muscle tissue contracts after receiving the electric stimulation, and the inherent elastic force of the spring provides dynamic mechanical stimulation;

[0035] The centripetal contraction force of the muscle tissue is calculated by multiplying the spring movable end displacement and the elastic coefficient, and the muscle tissue length is monitored in real time;

[0036] During the culture process, the muscle tissue strength increases, at this time, the spring position is adjusted by the micro servo cylinder, so that the muscle tissue length is kept unchanged.

[0037] The electric-force co-stimulation system comprises a ring-shaped distributed multi-electrode for electric stimulation of the muscle tissue, a spring for dynamic mechanical stimulation and centripetal contraction force measurement of the muscle tissue, and a micro servo cylinder for adjusting the spring position.

[0038] The annular distribution multi-electrode is controlled by a multi-channel electric stimulator, and an electric stimulation program of the upper computer software can generate electric fields with different intensity, pulse width and frequency.

[0039] The PDMS spring has a similar elastic coefficient to the engineered skeletal muscle tissue, and the elastic coefficient can be adjusted to be consistent with the muscle tissue by adjusting the spring turns, spacing, line width and thickness.

[0040] The electric-force co-stimulation system is transparent, allowing the visual monitoring system to collect information such as the displacement of the active end of the spring and the length of the muscle tissue in real time during the culture process.

[0041] The PDMS spring can respond to the muscle contraction force. Before electric stimulation, the product of the stretching amount and the elastic coefficient of the spring can reflect the passive contraction force of the muscle tissue. When electrically stimulated, the product of the dynamic stretching amount and the elastic coefficient of the spring can reflect the cardiac contraction force of the muscle tissue.

[0042] The micro servo cylinder can be controlled by the upper computer software through the USB controller to complete the extension and retraction motion. The stroke is 10mm, and the minimum single displacement is 5μm, which can accurately control the spring position while minimizing damage to the muscle tissue.

[0043] According to the length change of the muscle tissue measured by the visual monitoring system during growth, the micro servo cylinder is controlled to extend and retract by the program to adjust the muscle tissue length to the original length.

[0044] Without electric stimulation, the muscle will have passive contraction force due to the cell traction force in the muscle. If not constrained, the muscle will spontaneously atrophy, showing a shorter length, and even failure. Therefore, the spring can provide constraint, but when the spring and muscle are assembled to maintain the original length, the spring will inevitably be stretched, and the muscle will be shortened. However, since the spring is further stretched, the elastic force it generates is sufficient to counteract the passive force, so that the muscle does not fail, but still affects the function. Therefore, it is necessary to use a micro cylinder to adjust the spring position to keep the muscle at the original length. The adjustment process is to lengthen the spring, so that the muscle returns to the original length. The part of the spring that is stretched x the elastic coefficient is the passive contraction force of the muscle.

[0045] When the electrode generates an electric field, the muscle is electrically stimulated and produces regular cardiac contraction, driving the spring movement. During this process, the distance that the spring is stretched x the elastic coefficient is the cardiac contraction force of the muscle.

[0046] The structure of the host computer and the like involved in the utility model is a conventional selection, and the utility model has no innovation in software and programming, and only the structural technical features of hardware connection relationship and position relationship are protected, and the person skilled in the art can realize the function of the utility model and solve the technical problems of the utility model by combining the conventional programming logic with the structural features recorded in the utility model.

Claims

1. A human muscle training inspired myotissue electro-force co-stimulation system, comprising: electrodes, annularly distributed in the edge of a culture dish, connected with a multi-channel electrical stimulator; a spring, the movable end of which is connected with myotissue in the culture dish, and the fixed end is connected with a servo cylinder through a connecting piece; a servo cylinder, connected with a host computer through a controller.

2. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1, characterized in that, The electrodes are platinum sheets.

3. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1 or 2, characterized in that, The electrodes are platinum sheets with a length of 15 mm, a width of 5 mm, and a thickness of 0.1 mm.

4. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1 or 2, characterized in that, The electrodes are multiple and uniformly distributed.

5. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1, wherein, The spring is made of PDMS elastic material.

6. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1 or 3, characterized in that, The spring has 3 turns, a spring pitch of 1.5 mm, a spring wire width of 0.8 mm, and a spring wire thickness of 0.5 mm.

7. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1, wherein, One end of the myotissue is connected with the movable end of the spring, and the other end is connected with a microcolumn fixed on the surface of the culture dish.

8. The human muscle training inspired myotissue electro-force co-stimulation system of claim 1, wherein, The connecting piece is a connecting rod, so that the motion direction axis of the cylinder is parallel to the stretching direction axis of the spring.

9. The human muscle training inspired myotissue electro-force co-stimulation system according to claim 1, wherein, A visual monitoring system is further included, which is arranged directly above the culture dish.

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