Tissue engineering blood vessel culture method and device, electronic equipment and storage medium

Abstract

The invention belongs to the technical field of cell tissue culture, and discloses a tissue engineering blood vessel culture method and device, electronic equipment and a storage medium, and the method comprises the following steps: obtaining a target pressure waveform suitable for cell growth in tubular tissue, decomposing the target pressure waveform into a plurality of sine components through a Fourier transform method, the waveforms of the plurality of pressure waveform adjusting devices are respectively adjusted to be a plurality of corresponding sine components so as to be superposed to form the actual pressure waveform of the tubular tissue, the actual pressure waveform is used for stimulating cell growth in the tubular tissue to be reconstructed into the tissue engineering blood vessel, and the actual pressure waveform of the tubular tissue is monitored according to the target pressure waveform; by means of the Fourier transform method, the waveforms of the multiple pressure waveform adjusting devices are adjusted into the corresponding sine components, so that the pressure waveforms suitable for cell growth in the tubular tissue are obtained through adjustment, the culture efficiency of the tubular tissue is improved, the culture time is shortened, and the mechanical property of the tissue engineering blood vessel is improved.

Description

Technical Field

[0001] The present application relates to the technical field of cell tissue culture, and in particular to a tissue engineering blood vessel culture method, device, electronic equipment and storage medium. Background Art

[0002] The mechanical properties of tissue-engineered blood vessels are one of the important parameters for whether they can be implanted in vivo as grafts. Their mechanical properties are regulated by external mechanical stimulation during the culture process. Therefore, certain mechanical stimulation should be given during the culture of tissue-engineered blood vessels so that the tissue-engineered blood vessels can achieve the mechanical properties required for clinical transplantation. The loading of mechanical stimulation requires a specific pressure generating device, which can adjust the key parameters of the pressure waveform within a certain range, including the pressure peak and period, and finally obtain the set pressure waveform.

[0003] At present, the loading of mechanical stimulation of tissue engineering blood vessels mostly uses peristaltic pumps to extrude silicone tubes. As a mature product, peristaltic pumps have been widely used in pharmaceutical, food, chemical and other industries. Their advantage is that the transported liquid does not contact the pump body, but their adjustment ability is very limited in terms of pressure waveform regulation and control. The pressure waveform obtained by a single peristaltic pump is simple, which is quite different from the actual physiological environment in vivo.

[0004] Therefore, in order to solve the technical problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform consistent with the actual physiological environment, a tissue engineering blood vessel culture method, device, electronic equipment and storage medium are urgently needed. Summary of the invention

[0005] The purpose of the present application is to provide a tissue engineering blood vessel culture method, device, electronic device and storage medium. Through the Fourier transform method, the waveforms of multiple pressure waveform adjustment devices are adjusted to multiple sinusoidal components to superimpose the actual pressure waveforms that constitute the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels. The problem that the existing tissue engineering blood vessel culture methods are difficult to adjust to obtain a pressure waveform that is consistent with the actual physiological environment when adjusting the pressure waveform can be solved. The pressure waveform suitable for the growth of cells in the tubular tissue can be accurately adjusted, the culture efficiency of the tubular tissue is improved, the culture time is shortened, and the mechanical properties of the tissue engineering blood vessels are improved.

[0006] In a first aspect, the present application provides a tissue engineering blood vessel culture method for adjusting the pressure waveform of tubular tissue, comprising: obtaining a target pressure waveform suitable for cell growth in tubular tissue; Decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; respectively adjusting the waveforms of the plurality of pressure waveform adjusting devices to the corresponding plurality of sinusoidal components to superimpose the actual pressure waveform of the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; The actual pressure waveform of the tubular tissue is monitored according to the target pressure waveform.

[0007] The tissue engineering blood vessel culture method provided in the present application can realize the regulation of the pressure waveform of the tubular tissue. Through the Fourier transform method, the waveforms of multiple pressure waveform regulating devices are adjusted to multiple sinusoidal components to superimpose the actual pressure waveform that constitutes the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels. This solves the problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform that is consistent with the actual physiological environment when adjusting the pressure waveform. It can accurately adjust the pressure waveform suitable for the growth of cells in the tubular tissue, improve the culture efficiency of the tubular tissue, shorten the culture time, and enhance the mechanical properties of the tissue engineering blood vessels.

[0008] Optionally, the pressure waveform regulating device is specifically a syringe pump, a diaphragm pump or a peristaltic pump.

[0009] Optionally, the target pressure waveform is decomposed into a plurality of sinusoidal components by a Fourier transform method, including: According to the number of the pressure waveform regulating devices, a corresponding decomposition number is selected; The target pressure waveform is decomposed into a plurality of sinusoidal components based on the decomposition quantity by the Fourier transform method.

[0010] Optionally, the target pressure waveform is decomposed into a plurality of sinusoidal components based on the decomposition quantity by the Fourier transform method, including: Setting a Fourier transform formula corresponding to the decomposition quantity; According to the Fourier transform formula, the target pressure waveform is decomposed into a plurality of sinusoidal components.

[0011] The tissue engineering blood vessel culture method provided in the present application can adjust the pressure waveform of the tubular tissue, set a Fourier transform formula corresponding to the decomposition number, decompose the target pressure waveform into multiple sinusoidal components, and adjust the waveforms of multiple pressure waveform adjustment devices to the corresponding multiple sinusoidal components, thereby adjusting the actual pressure waveform of the tubular tissue to the target pressure waveform to promote cell growth in the tubular tissue, improve the culture efficiency of the tubular tissue, shorten the culture time, and enhance the mechanical properties of the tissue engineering blood vessels.

[0012] Optionally, the Fourier transform formula is specifically: ; in, is the target pressure waveform; is the sinusoidal component; is a sinusoidal waveform; k is the kth sinusoidal component, K is the number of decompositions, 1≤k≤K; is the DC component; is the amplitude of the kth sinusoidal component; is the phase of the kth sinusoidal component; For time; is the waveform frequency, , T is the period, is the angular frequency.

[0013] Optionally, monitoring the actual pressure waveform of the tubular tissue according to the target pressure waveform includes: Calculating a deviation between the actual pressure waveform and the target pressure waveform; The actual pressure waveform of the tubular tissue is monitored according to the magnitude relationship between the deviation and a preset error threshold.

[0014] The tissue engineering blood vessel culture method provided in the present application can adjust the pressure waveform of the tubular tissue. By comparing the preset error threshold with the deviation between the actual pressure waveform and the target pressure waveform, the actual pressure waveform of the tubular tissue is monitored so that the tubular tissue is maintained in a pressure waveform environment suitable for generation, which is beneficial to improving the culture efficiency of the tubular tissue.

[0015] Optionally, monitoring the actual pressure waveform of the tubular tissue according to the magnitude relationship between the deviation and a preset error threshold value includes: Determining whether the deviation is less than or equal to the preset error threshold; If so, determining that the actual pressure waveform is in a use state that promotes cell growth in the tubular tissue; If not, adjust the waveform of one or more of the pressure waveform adjustment devices so that the adjusted deviation is less than or equal to the preset error threshold.

[0016] In a second aspect, the present application provides a tissue engineering blood vessel culture device, comprising: an acquisition module, used for acquiring a target pressure waveform suitable for cell growth in tubular tissue; A decomposition module, used for decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; A regulating module, used for respectively regulating the waveforms of the plurality of pressure waveform regulating devices to the corresponding plurality of sinusoidal components, so as to superimpose the actual pressure waveform of the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; A monitoring module is used to monitor the actual pressure waveform of the tubular tissue according to the target pressure waveform.

[0017] The tissue engineering blood vessel culture device adjusts the waveforms of multiple pressure waveform adjustment devices into multiple sinusoidal components through the Fourier transform method to superimpose the actual pressure waveforms that constitute the tubular tissue, so as to stimulate the growth of cells in the tubular tissue to reconstruct into tissue engineering blood vessels. The problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform that matches the actual physiological environment when adjusting the pressure waveform can be solved. The pressure waveform suitable for the growth of cells in the tubular tissue can be accurately adjusted, the culture efficiency of the tubular tissue is improved, the culture time is shortened, and the mechanical properties of the tissue engineering blood vessels are improved.

[0018] In a third aspect, the present application provides an electronic device, comprising a processor and a memory, wherein the memory stores a computer program executable by the processor, and when the processor executes the computer program, it runs the steps in the tissue engineering blood vessel culture method described above.

[0019] In a fourth aspect, the present application provides a computer-readable storage medium having a computer program stored thereon, and when the computer program is executed by a processor, the steps in the tissue engineering blood vessel culture method described above are executed.

[0020] Beneficial effects: The tissue engineering blood vessel culture method, device, electronic device and storage medium provided in the present application, through the Fourier transform method, adjust the waveforms of multiple pressure waveform adjustment devices into multiple sinusoidal components to superimpose the actual pressure waveforms that constitute the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels, thereby solving the problem that the existing tissue engineering blood vessel culture methods are difficult to adjust the pressure waveform to obtain a pressure waveform that is consistent with the actual physiological environment, and can accurately adjust the pressure waveform suitable for the growth of cells in the tubular tissue, thereby improving the culture efficiency of the tubular tissue, shortening the culture time, and improving the mechanical properties of the tissue engineering blood vessels. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a flow chart of the tissue engineering blood vessel culture method provided in the embodiments of the present application.

[0022] Figure 2 This is a schematic diagram of the structure of the tissue engineering blood vessel culture device provided in the embodiment of the present application.

[0023] Figure 3 A schematic diagram of the structure of an electronic device provided in an embodiment of the present application.

[0024] Figure 4 The relationship triangle of the Fourier series provided in the embodiment of the present application.

[0025] Explanation of reference numerals: 1. Acquisition module; 2. Decomposition module; 3. Adjustment module; 4. Monitoring module; 301. Processor; 302. Memory; 303. Communication bus. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. The components of the embodiments of the present application described and shown in the drawings here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present application provided in the drawings is not intended to limit the scope of the application claimed for protection, but merely represents the selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present application.

[0027] It should be noted that similar reference numerals and letters represent similar items in the following drawings, so once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings. At the same time, in the description of this application, the terms "first", "second", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance.

[0028] Please refer to Figure 1 , Figure 1 A tissue engineering blood vessel culture method in some embodiments of the present application is used to adjust the pressure waveform of tubular tissue, comprising the steps of: Step S101, obtaining a target pressure waveform suitable for cell growth in tubular tissue; Step S102, decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; Step S103, respectively adjusting the waveforms of the multiple pressure waveform adjustment devices to corresponding multiple sinusoidal components to superimpose the actual pressure waveforms constituting the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; Step S104: monitoring the actual pressure waveform of the tubular tissue according to the target pressure waveform.

[0029] The tissue engineering blood vessel culture method adjusts the waveforms of multiple pressure waveform adjustment devices into multiple sinusoidal components through the Fourier transform method to superimpose the actual pressure waveforms that constitute the tubular tissue, so as to stimulate the growth of cells in the tubular tissue to reconstruct into tissue engineering blood vessels. The problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform that matches the actual physiological environment when adjusting the pressure waveform is solved. The pressure waveform suitable for the growth of cells in the tubular tissue can be accurately adjusted, the culture efficiency of the tubular tissue is improved, the culture time is shortened, and the mechanical properties of the tissue engineering blood vessels are improved.

[0030] Specifically, in step S101, a target pressure waveform suitable for cell growth in tubular tissue is obtained, which can be obtained by analyzing the pressure changes of healthy blood vessels under physiological conditions, or customized according to the needs of specific patients. For example, for patients who need coronary artery bypass grafting, the pressure waveform of their healthy coronary arteries or the healthy coronary arteries of other healthy people can be collected as the target pressure waveform. The tubular tissue is reconstructed by cell growth.

[0031] The tissue engineering blood vessel culture method is not only applicable to tubular tissues, but also to tissues of other shapes, by adjusting the pressure waveform of tissues of other shapes as the target pressure waveform, thereby stimulating cell growth of tissues of other shapes.

[0032] In some embodiments, tubular material can be used instead of tubular tissue. The tubular material can be existing mature tissue (before the tissue is implanted into the body, it is given mechanical stimulation training to adapt to the physiological environment of the human body to meet the requirements of transplantation) or scaffold material (the scaffold material is inoculated with cells, which can grow and reconstruct into tissue-engineered blood vessels under the pressure environment of the target pressure waveform).

[0033] Specifically, in step S102, the target pressure waveform is decomposed into multiple sinusoidal components by Fourier transform method, including: According to the number of pressure waveform adjustment devices, select the corresponding decomposition number; The target pressure waveform is decomposed into multiple sinusoidal components based on the decomposition quantity by Fourier transform method.

[0034] In step S102, an appropriate decomposition number is selected according to the number of pressure waveform adjustment devices, and then the target pressure waveform is decomposed into a corresponding number of sinusoidal components through Fourier transform. The superposition of the corresponding number of sinusoidal components can approximately represent the original target pressure waveform, so as to simulate a pressure environment suitable for cell growth in tubular tissue. Because each adjustment device will be responsible for simulating a sinusoidal component, the number of adjustment devices directly determines the number of sinusoidal components that can be decomposed.

[0035] Among them, the Fourier transform method is a powerful mathematical tool that can decompose any periodic signal into a superposition of a series of sine waves.

[0036] The pressure waveform regulating device is specifically a device for regulating the pressure waveform, such as a syringe pump, a diaphragm pump or a peristaltic pump. These devices can be adjusted to obtain a sinusoidal waveform. They each have unique characteristics and advantages and can meet different culture requirements. A suitable pressure waveform regulating device can be selected according to specific culture requirements. Among them, the syringe pump, the diaphragm pump or the peristaltic pump are prior arts and will not be described in detail here.

[0037] Specifically, in step S102, the target pressure waveform is decomposed into a plurality of sinusoidal components based on the decomposition quantity by Fourier transform method, including: Set the Fourier transform formula corresponding to the number of decompositions; According to the Fourier transform formula, the target pressure waveform is decomposed into multiple sinusoidal components.

[0038] In step S102, the Fourier transform method is used to achieve precise control and regulation of the pressure waveform during the tissue engineering blood vessel culture process. First, the corresponding decomposition number is selected according to the number of pressure waveform adjustment devices actually available. Then, according to the decomposition number, the corresponding Fourier transform formula is selected (the parameters in the Fourier transform formula are set according to the decomposition number). According to the Fourier transform formula, the target pressure waveform is decomposed into multiple sinusoidal components.

[0039] Among them, the Fourier transform formula is specifically: ; (1) in, is the target pressure waveform; is the sinusoidal component; is a sinusoidal waveform; k is the kth sinusoidal component, K is the number of decompositions, 1≤k≤K; is the DC component; is the amplitude of the kth sinusoidal component; is the phase of the kth sinusoidal component; For time; is the frequency, , T is the period, is the angular frequency.

[0040] The inverse transform can be used to restore the waveform of the signal based on the amplitude and phase, so the amplitude and phase contain all the information of the signal. The function of amplitude with respect to frequency is called spectrum, and the function of phase with respect to frequency is called phase spectrum.

[0041] above , , , These four parameters can be calculated through calculus, and the error between the waveform obtained by superimposing different numbers of waveforms and the ideal waveform (target pressure waveform) can also be calculated and analyzed, and then the appropriate number of waveforms can be selected according to the actual accuracy requirements, structural complexity and cost.

[0042] The general form of the Fourier series is: ; (2) in, is the DC component of the periodic signal, is the cosine amplitude of the kth cosine component, is the sinusoidal amplitude of the kth sinusoidal component; For formula (2), both ends of the equal sign are arrive Integrate item by item and calculate: ; use Multiply both ends of equation (2) and get arrive Points can be obtained: ; Where n is the nth sinusoidal component.

[0043] Calculated by the above formula: ; (3) Similarly, use Multiply both ends of equation (2) and get Points can be obtained: ; (4) Combining the same frequency terms in formula (2) yields: ; (5) or, ; (6) Here we take the decomposition of a periodic signal into sinusoidal components in formula (6) as an example, where: is the amplitude of the kth sinusoidal component, is the phase of the kth sinusoidal component. Similarly, when the periodic signal is decomposed into cosine components, is the amplitude of the kth cosine component, is the phase of the kth cosine component.

[0044] from Figure 4 The relationship between the coefficients in the Fourier series is obtained as follows: ; In summary, the Fourier transform formula, i.e., formula (1), is calculated and obtained. By using mathematical software or a mathematical toolkit, the target function (target pressure waveform) is input into formula (1) to obtain the required parameters. By adjusting the value of K, i.e., the number of decomposed sinusoidal components, a balance can be found between accuracy and complexity. The mathematical software or mathematical toolkit is a prior art and will not be described in detail here.

[0045] For example, assuming that three pressure waveform adjustment devices are available, K=3 can be selected to decompose the target pressure waveform into three main sinusoidal components, and the three sinusoidal components are synthesized and superimposed so that the actual pressure waveform passing through the tubular tissue reaches a fit of 95% or more than 99% of the target pressure waveform, thereby stimulating the cells in the tubular tissue to grow rapidly and reconstruct into tissue-engineered blood vessels.

[0046] Specifically, in step S103, based on the multiple sinusoidal components calculated by the above-mentioned Fourier transform formula, the waveforms of multiple pressure waveform adjustment devices are respectively adjusted to corresponding sinusoidal components to superimpose the actual pressure waveforms that constitute the tubular tissue, so that the actual pressure waveform of the tubular tissue is close to the target pressure waveform, thereby simulating a pressure environment suitable for cell growth in the tubular tissue to stimulate the cell growth in the tubular tissue to reconstruct into tissue engineering blood vessels.

[0047] Specifically, in step S104, the actual pressure waveform of the tubular tissue is monitored according to the target pressure waveform, including: Calculate the deviation between the actual pressure waveform and the target pressure waveform; The actual pressure waveform of the tubular tissue is monitored based on the magnitude relationship between the deviation and a preset error threshold.

[0048] In step S104, the deviation between the actual pressure waveform and the target pressure waveform is calculated, for example, a point-to-point deviation calculation method (i.e., calculating the absolute value of the difference between the actual pressure waveform and the target pressure waveform at multiple consecutive time points) or a root mean square error statistical method (i.e., calculating the absolute value of the difference between the variance of the actual pressure waveform and the variance of the target pressure waveform in the same time period, and the time period can be set according to actual needs) can be used to compare the calculated deviation with a preset error threshold, and the actual pressure waveform of the tubular tissue is monitored according to the size relationship between the deviation and the preset error threshold. The error threshold can be set according to specific culture requirements and blood vessel types.

[0049] Specifically, in step S104, the actual pressure waveform of the tubular tissue is monitored according to the magnitude relationship between the deviation and the preset error threshold, including: Determine whether the deviation is less than or equal to a preset error threshold; If so, determining that the actual pressure waveform is in a use state that promotes cell growth in the tubular tissue; If not, the waveform of one or more pressure waveform adjustment devices is adjusted so that the adjusted deviation is less than or equal to a preset error threshold.

[0050] In step S104, the deviation is compared with a preset error threshold to determine whether the actual pressure waveform is within an acceptable range, that is, to determine whether the deviation is less than or equal to the preset error threshold (for example, when a point-to-point deviation calculation method is adopted, the absolute value of the difference between the actual pressure waveform and the target pressure waveform at multiple consecutive time points can be calculated (if only the difference between the actual pressure waveform and the target pressure waveform at one time point is calculated, the calculation result will be affected by frequent calculations) to determine whether all absolute values ​​are greater than the preset error threshold. If all absolute values ​​are less than or equal to the preset error threshold, it is considered that the actual pressure waveform is within an acceptable range; otherwise, it is considered that the actual pressure waveform is not within an acceptable range; or, when a root mean square error statistical method is used, it is necessary to calculate the absolute value of the difference between the variance of the actual pressure waveform and the variance of the target pressure waveform in the same time period. If the absolute value is less than or equal to the preset error threshold, it is considered that the actual pressure waveform is within an acceptable range; otherwise, it is considered that the actual pressure waveform is not within an acceptable range).

[0051] When the deviation is less than or equal to a preset error threshold, it is determined that the corresponding actual pressure waveform is within an acceptable range, and that the corresponding actual pressure waveform is in a usage state for promoting cell growth in tubular tissue, and there is no need to adjust the actual pressure waveform.

[0052] When the deviation is greater than a preset error threshold, it is determined that the actual pressure waveform is not within an acceptable range, and that the corresponding actual pressure waveform is in a usage state that cannot promote cell growth in tubular tissue, and that the actual pressure waveform needs to be adjusted. One or more devices are selected from the pressure waveform adjustment devices for waveform adjustment so that the deviation between the adjusted actual pressure waveform and the target pressure waveform is less than or equal to the preset error threshold (for example, the pressure waveform adjustment devices can be sorted in descending order according to the amplitude of the waveform of each pressure waveform adjustment device, and according to the sorting result, the pressure waveform adjustment devices are selected from front to back to perform waveform adjustment within the allowable adjustment range so that the deviation between the adjusted actual pressure waveform and the target pressure waveform is minimized. If the deviation between the adjusted actual pressure waveform and the target pressure waveform still cannot be made less than or equal to the preset error threshold, then while maintaining the adjusted waveform of the selected pressure waveform adjustment device, the next pressure waveform adjustment device is selected for waveform adjustment until the deviation between the adjusted actual pressure waveform and the target pressure waveform is less than or equal to the preset error threshold; wherein the allowable adjustment range includes at least one of an amplitude adjustment range, a frequency adjustment range, and a phase adjustment range, and the specific range can be set according to actual needs).

[0053] As can be seen from the above, the tissue engineering blood vessel culture method obtains a target pressure waveform suitable for cell growth in tubular tissue, decomposes the target pressure waveform into multiple sinusoidal components through the Fourier transform method, and adjusts the waveforms of multiple pressure waveform adjustment devices to corresponding multiple sinusoidal components respectively, so as to superimpose the actual pressure waveform constituting the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, and monitors the actual pressure waveform of the tubular tissue according to the target pressure waveform; thus, the waveforms of multiple pressure waveform adjustment devices are adjusted to multiple sinusoidal components through the Fourier transform method, so as to superimpose the actual pressure waveform constituting the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, thereby solving the problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform consistent with the actual physiological environment, and can accurately adjust the pressure waveform suitable for cell growth in the tubular tissue, thereby improving the culture efficiency of the tubular tissue, shortening the culture time, and improving the mechanical properties of the tissue engineering blood vessel.

[0054] refer to Figure 2 The present application provides a tissue engineering blood vessel culture device for adjusting the pressure waveform of tubular tissue, comprising: An acquisition module 1 is used to acquire a target pressure waveform suitable for cell growth in tubular tissue; A decomposition module 2, used for decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; The regulating module 3 is used to respectively regulate the waveforms of the multiple pressure waveform regulating devices into corresponding multiple sinusoidal components, so as to superimpose the actual pressure waveforms constituting the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; The monitoring module 4 is used to monitor the actual pressure waveform of the tubular tissue according to the target pressure waveform.

[0055] The tissue engineering blood vessel culture device adjusts the waveforms of multiple pressure waveform adjustment devices into multiple sinusoidal components through the Fourier transform method to superimpose the actual pressure waveforms that constitute the tubular tissue, so as to stimulate the growth of cells in the tubular tissue to reconstruct into tissue engineering blood vessels. The problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform that matches the actual physiological environment when adjusting the pressure waveform can be solved. The pressure waveform suitable for the growth of cells in the tubular tissue can be accurately adjusted, the culture efficiency of the tubular tissue is improved, the culture time is shortened, and the mechanical properties of the tissue engineering blood vessels are improved.

[0056] Specifically, when the acquisition module 1 is executed, a target pressure waveform suitable for cell growth in the tubular tissue is acquired. This target pressure waveform can be obtained by analyzing the pressure changes of healthy blood vessels under physiological conditions, or can be customized according to the needs of specific patients. For example, for patients who need coronary artery bypass grafting, the pressure waveform of their healthy coronary arteries or the healthy coronary arteries of other healthy people can be collected as the target pressure waveform. The tubular tissue is reconstructed by cell growth.

[0057] The tissue engineering blood vessel culture method is not only applicable to tubular tissues, but also to tissues of other shapes, by adjusting the pressure waveform of tissues of other shapes as the target pressure waveform, thereby stimulating cell growth of tissues of other shapes.

[0058] In some embodiments, tubular material can be used instead of tubular tissue. The tubular material can be existing mature tissue (before the tissue is implanted into the body, it is given mechanical stimulation training to adapt to the physiological environment of the human body to meet the requirements of transplantation) or scaffold material (the scaffold material is inoculated with cells, which can grow and reconstruct into tissue-engineered blood vessels under the pressure environment of the target pressure waveform).

[0059] Specifically, when the decomposition module 2 decomposes the target pressure waveform into multiple sinusoidal components by Fourier transform method, it executes: According to the number of pressure waveform adjustment devices, select the corresponding decomposition number; The target pressure waveform is decomposed into multiple sinusoidal components based on the decomposition quantity by Fourier transform method.

[0060] When the decomposition module 2 is executed, it selects an appropriate decomposition number according to the number of pressure waveform adjustment devices, and then decomposes the target pressure waveform into a corresponding number of sinusoidal components through Fourier transform. The superposition of the corresponding number of sinusoidal components can approximately represent the original target pressure waveform, so as to simulate a pressure environment suitable for cell growth in tubular tissue. Because each adjustment device will be responsible for simulating a sinusoidal component, the number of adjustment devices directly determines the number of sinusoidal components that can be decomposed.

[0061] Among them, the Fourier transform method is a powerful mathematical tool that can decompose any periodic signal into a superposition of a series of sine waves.

[0062] The pressure waveform regulating device is specifically a device for regulating the pressure waveform, such as a syringe pump, a diaphragm pump or a peristaltic pump. These devices can be adjusted to obtain a sinusoidal waveform. They each have unique characteristics and advantages and can meet different culture requirements. A suitable pressure waveform regulating device can be selected according to specific culture requirements. Among them, the syringe pump, the diaphragm pump or the peristaltic pump are prior arts and will not be described in detail here.

[0063] Specifically, when the decomposition module 2 decomposes the target pressure waveform into multiple sinusoidal components based on the decomposition quantity by Fourier transform method, it executes: Set the Fourier transform formula corresponding to the number of decompositions; According to the Fourier transform formula, the target pressure waveform is decomposed into multiple sinusoidal components.

[0064] When the decomposition module 2 is executed, the Fourier transform method is used to achieve precise control and adjustment of the pressure waveform during the tissue engineering blood vessel culture process. First, the corresponding decomposition number is selected according to the number of pressure waveform adjustment devices actually available, and then the corresponding Fourier transform formula is selected according to the decomposition number (the parameters in the Fourier transform formula are set according to the decomposition number). According to the Fourier transform formula, the target pressure waveform is decomposed into multiple sinusoidal components.

[0065] Among them, the Fourier transform formula is specifically: ; (1) in, is the target pressure waveform; is the sinusoidal component; is a sinusoidal waveform; k is the kth sinusoidal component, K is the number of decompositions, 1≤k≤K; is the DC component; is the amplitude of the kth sinusoidal component; is the phase of the kth sinusoidal component; For time; is the frequency, , T is the period, is the angular frequency.

[0066] The inverse transform can be used to restore the waveform of the signal based on the amplitude and phase, so the amplitude and phase contain all the information of the signal. The function of amplitude with respect to frequency is called spectrum, and the function of phase with respect to frequency is called phase spectrum.

[0067] above , , , These four parameters can be calculated through calculus, and the error between the waveform obtained by superimposing different numbers of waveforms and the ideal waveform (target pressure waveform) can also be calculated and analyzed, and then the appropriate number of waveforms can be selected according to the actual accuracy requirements, structural complexity and cost.

[0068] The general form of the Fourier series is: ; (2) in, is the DC component of the periodic signal, is the cosine amplitude of the kth cosine component, is the sinusoidal amplitude of the kth sinusoidal component; For formula (2), both ends of the equal sign are arrive Integrate item by item and calculate: ; use Multiply both ends of equation (2) and get arrive Points can be obtained: ; Where n is the nth sinusoidal component.

[0069] Calculated by the above formula: ; (3) Similarly, use Multiply both ends of equation (2) and get arrive Points can be obtained: ; (4) Combining the same frequency terms in formula (2) yields: ; (5) or, ; (6) Here we take the decomposition of a periodic signal into sinusoidal components in formula (6) as an example, where: is the amplitude of the kth sinusoidal component, is the phase of the kth sinusoidal component. Similarly, when the periodic signal is decomposed into cosine components, is the amplitude of the kth cosine component, is the phase of the kth cosine component.

[0070] from Figure 4 The relationship between the coefficients in the Fourier series is obtained as follows: ; In summary, the Fourier transform formula, i.e., formula (1), is calculated and obtained. By using mathematical software or a mathematical toolkit, the target function (target pressure waveform) is input into formula (1) to obtain the required parameters. By adjusting the value of K, i.e., the number of decomposed sinusoidal components, a balance can be found between accuracy and complexity. The mathematical software or mathematical toolkit is a prior art and will not be described in detail here.

[0071] For example, assuming that three pressure waveform adjustment devices are available, K=3 can be selected to decompose the target pressure waveform into three main sinusoidal components, and the three sinusoidal components are synthesized and superimposed so that the actual pressure waveform passing through the tubular tissue reaches a fit of 95% or more than 99% of the target pressure waveform, thereby stimulating the cells in the tubular tissue to grow rapidly and reconstruct into tissue-engineered blood vessels.

[0072] Specifically, when the adjustment module 3 is executed, it adjusts the waveforms of multiple pressure waveform adjustment devices to corresponding sinusoidal components according to the multiple sinusoidal components calculated by the above-mentioned Fourier transform formula, so as to superimpose the actual pressure waveforms that constitute the tubular tissue, so that the actual pressure waveform of the tubular tissue is close to the target pressure waveform, thereby simulating a pressure environment suitable for cell growth in the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into tissue engineering blood vessels.

[0073] Specifically, when the monitoring module 4 monitors the actual pressure waveform of the tubular tissue according to the target pressure waveform, it executes: Calculate the deviation between the actual pressure waveform and the target pressure waveform; The actual pressure waveform of the tubular tissue is monitored based on the magnitude relationship between the deviation and a preset error threshold.

[0074] When the monitoring module 4 is executed, it calculates the deviation between the actual pressure waveform and the target pressure waveform, for example, it can use a point-to-point deviation calculation method (i.e., calculating the absolute value of the difference between the actual pressure waveform and the target pressure waveform at multiple consecutive time points) or a root mean square error statistical method (i.e., calculating the absolute value of the difference between the variance of the actual pressure waveform and the variance of the target pressure waveform in the same time period, and the time period can be set according to actual needs), etc., compare the calculated deviation with a preset error threshold, and monitor the actual pressure waveform of the tubular tissue according to the size relationship between the deviation and the preset error threshold. Among them, the error threshold can be set according to specific culture requirements and blood vessel types.

[0075] Specifically, when the monitoring module 4 monitors the actual pressure waveform of the tubular tissue according to the magnitude relationship between the deviation and the preset error threshold, the monitoring module 4 executes: Determine whether the deviation is less than or equal to a preset error threshold; If so, determining that the actual pressure waveform is in a use state that promotes cell growth in the tubular tissue; If not, the waveform of one or more pressure waveform adjustment devices is adjusted so that the adjusted deviation is less than or equal to a preset error threshold.

[0076] When the monitoring module 4 is executed, the deviation is compared with a preset error threshold to determine whether the actual pressure waveform is within an acceptable range, that is, whether the deviation is less than or equal to the preset error threshold (for example, when a point-to-point deviation calculation method is adopted, the absolute value of the difference between the actual pressure waveform and the target pressure waveform at multiple consecutive time points can be calculated (if only the difference between the actual pressure waveform and the target pressure waveform at one time point is calculated, the calculation result will be affected by frequent calculations) to determine whether all absolute values ​​are greater than the preset error threshold. If all absolute values ​​are less than or equal to the preset error threshold, it is considered that the actual pressure waveform is within an acceptable range, otherwise, it is considered that the actual pressure waveform is not within an acceptable range; or, when a root mean square error statistical method is used, it is necessary to calculate the absolute value of the difference between the variance of the actual pressure waveform and the variance of the target pressure waveform in the same time period. If the absolute value is less than or equal to the preset error threshold, it is considered that the actual pressure waveform is within an acceptable range, otherwise, it is considered that the actual pressure waveform is not within an acceptable range).

[0077] When the deviation is less than or equal to a preset error threshold, it is determined that the corresponding actual pressure waveform is within an acceptable range, and that the corresponding actual pressure waveform is in a usage state for promoting cell growth in tubular tissue, and there is no need to adjust the actual pressure waveform.

[0078] When the deviation is greater than a preset error threshold, it is determined that the actual pressure waveform is not within an acceptable range, and that the corresponding actual pressure waveform is in a usage state that cannot promote cell growth in tubular tissue, and that the actual pressure waveform needs to be adjusted. One or more devices are selected from the pressure waveform adjustment devices for waveform adjustment so that the deviation between the adjusted actual pressure waveform and the target pressure waveform is less than or equal to the preset error threshold (for example, the pressure waveform adjustment devices can be sorted in descending order according to the amplitude of the waveform of each pressure waveform adjustment device, and according to the sorting result, the pressure waveform adjustment devices are selected from front to back to perform waveform adjustment within the allowable adjustment range so that the deviation between the adjusted actual pressure waveform and the target pressure waveform is minimized. If the deviation between the adjusted actual pressure waveform and the target pressure waveform still cannot be made less than or equal to the preset error threshold, then while maintaining the adjusted waveform of the selected pressure waveform adjustment device, the next pressure waveform adjustment device is selected for waveform adjustment until the deviation between the adjusted actual pressure waveform and the target pressure waveform is less than or equal to the preset error threshold; wherein the allowable adjustment range includes at least one of an amplitude adjustment range, a frequency adjustment range, and a phase adjustment range, and the specific range can be set according to actual needs).

[0079] As can be seen from the above, the tissue engineering blood vessel culture device obtains a target pressure waveform suitable for cell growth in tubular tissue, decomposes the target pressure waveform into multiple sinusoidal components through the Fourier transform method, and adjusts the waveforms of multiple pressure waveform adjustment devices to corresponding multiple sinusoidal components respectively, so as to superimpose the actual pressure waveform that constitutes the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, and monitors the actual pressure waveform of the tubular tissue according to the target pressure waveform; thus, through the Fourier transform method, the waveforms of multiple pressure waveform adjustment devices are adjusted to multiple sinusoidal components, so as to superimpose the actual pressure waveform that constitutes the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, thereby solving the problem that the existing tissue engineering blood vessel culture method is difficult to adjust the pressure waveform to obtain a pressure waveform that is consistent with the actual physiological environment, and can accurately adjust the pressure waveform suitable for cell growth in the tubular tissue, thereby improving the culture efficiency of the tubular tissue, shortening the culture time, and improving the mechanical properties of the tissue engineering blood vessel.

[0080] Please refer to Figure 3 , Figure 3A schematic diagram of the structure of an electronic device provided in an embodiment of the present application. The present application provides an electronic device, including: a processor 301 and a memory 302. The processor 301 and the memory 302 are interconnected and communicate with each other through a communication bus 303 and / or other forms of connection mechanisms (not shown). The memory 302 stores a computer program executable by the processor 301. When the electronic device is running, the processor 301 executes the computer program to execute the tissue engineering blood vessel culture method in any optional implementation of the above embodiment to achieve the following functions: obtaining a target pressure waveform suitable for cell growth in tubular tissue, decomposing the target pressure waveform into multiple sinusoidal components through a Fourier transform method, respectively adjusting the waveforms of multiple pressure waveform adjustment devices into corresponding multiple sinusoidal components, so as to superimpose an actual pressure waveform constituting the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, and monitoring the actual pressure waveform of the tubular tissue according to the target pressure waveform.

[0081] An embodiment of the present application provides a computer-readable storage medium having a computer program stored thereon. When the computer program is executed by a processor, the tissue engineering blood vessel culture method in any optional implementation of the above-mentioned embodiment is executed to achieve the following functions: obtaining a target pressure waveform suitable for cell growth in tubular tissue, decomposing the target pressure waveform into multiple sinusoidal components through a Fourier transform method, respectively adjusting the waveforms of multiple pressure waveform adjustment devices into corresponding multiple sinusoidal components to superimpose an actual pressure waveform that constitutes the tubular tissue, so as to stimulate the cell growth in the tubular tissue to reconstruct into a tissue engineering blood vessel, and monitoring the actual pressure waveform of the tubular tissue according to the target pressure waveform. Among them, the storage medium can be implemented by any type of volatile or non-volatile storage device or a combination thereof, such as static random access memory (SRAM), electrically erasable programmable read-only memory (EEPROM), erasable programmable read-only memory (EPROM), programmable red-only memory (PROM), read-only memory (ROM), magnetic storage, flash memory, magnetic disk or optical disk.

[0082] In the embodiments provided in the present application, it should be understood that the disclosed devices and methods can be implemented in other ways. The device embodiments described above are merely schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation. For example, multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some communication interfaces, and the indirect coupling or communication connection of the devices or units can be electrical, mechanical or other forms.

[0083] In addition, the units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, and may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0084] Furthermore, the functional modules in the various embodiments of the present application may be integrated together to form an independent part, or each module may exist separately, or two or more modules may be integrated to form an independent part.

[0085] In this document, relational terms such as first and second, etc. are used merely to distinguish one entity or operation from another entity or operation, but do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0086] The above description is only an embodiment of the present application and is not intended to limit the protection scope of the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A tissue engineering blood vessel culture method for regulating the pressure waveform of tubular tissue, characterized in that: Includes steps: obtaining a target pressure waveform suitable for cell growth in tubular tissue; Decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; respectively adjusting the waveforms of the plurality of pressure waveform adjusting devices to the corresponding plurality of sinusoidal components to superimpose the actual pressure waveform of the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; The actual pressure waveform of the tubular tissue is monitored according to the target pressure waveform.

2. The tissue engineering blood vessel culture method according to claim 1, characterized in that: The pressure waveform regulating device is specifically a syringe pump, a diaphragm pump or a peristaltic pump.

3. The tissue engineering blood vessel culture method according to claim 1, characterized in that: The target pressure waveform is decomposed into multiple sinusoidal components by Fourier transform method, including: According to the number of the pressure waveform regulating devices, a corresponding decomposition number is selected; The target pressure waveform is decomposed into a plurality of sinusoidal components based on the decomposition quantity by the Fourier transform method.

4. The tissue engineering blood vessel culture method according to claim 3, characterized in that: By means of the Fourier transform method, based on the decomposition quantity, the target pressure waveform is decomposed into a plurality of sinusoidal components, including: Setting a Fourier transform formula corresponding to the decomposition quantity; According to the Fourier transform formula, the target pressure waveform is decomposed into a plurality of sinusoidal components.

5. The tissue engineering blood vessel culture method according to claim 4, characterized in that: The Fourier transform formula is specifically: ； in, is the target pressure waveform; is the sinusoidal component; is a sinusoidal waveform; k is the kth sinusoidal component, K is the number of decompositions, 1≤k≤K; is the DC component; is the amplitude of the kth sinusoidal component; is the phase of the kth sinusoidal component; For time; is the waveform frequency, , T is the period, is the angular frequency.

6. The tissue engineering blood vessel culture method according to claim 1, characterized in that: Monitoring the actual pressure waveform of the tubular tissue according to the target pressure waveform includes: Calculating a deviation between the actual pressure waveform and the target pressure waveform; The actual pressure waveform of the tubular tissue is monitored according to the magnitude relationship between the deviation and a preset error threshold.

7. The tissue engineering blood vessel culture method according to claim 6, characterized in that: According to the magnitude relationship between the deviation and a preset error threshold, the actual pressure waveform of the tubular tissue is monitored, including: Determining whether the deviation is less than or equal to the preset error threshold; If so, determining that the actual pressure waveform is in a use state that promotes cell growth in the tubular tissue; If not, adjust the waveform of one or more of the pressure waveform adjustment devices so that the adjusted deviation is less than or equal to the preset error threshold.

8. A tissue engineering blood vessel culture device for adjusting the pressure waveform of tubular tissue, characterized in that: include: an acquisition module, used for acquiring a target pressure waveform suitable for cell growth in tubular tissue; A decomposition module, used for decomposing the target pressure waveform into multiple sinusoidal components by Fourier transform method; A regulating module, used for respectively regulating the waveforms of the plurality of pressure waveform regulating devices to the corresponding plurality of sinusoidal components, so as to superimpose the actual pressure waveform of the tubular tissue, so as to stimulate the growth of cells in the tubular tissue and reconstruct them into tissue engineering blood vessels; A monitoring module is used to monitor the actual pressure waveform of the tubular tissue according to the target pressure waveform.

9. An electronic device, characterized in that: The method comprises a processor and a memory, wherein the memory stores a computer program executable by the processor, and when the processor executes the computer program, the steps in the tissue engineering blood vessel culture method according to any one of claims 1 to 7 are executed.

10. A computer-readable storage medium having a computer program stored thereon, characterized in that: When the computer program is executed by a processor, the steps in the tissue engineering blood vessel culture method according to any one of claims 1 to 7 are executed.

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