Method for evaluating degradation process of porous elastic stent based on shear wave attenuation characteristics

Abstract

The invention belongs to the technical field of tissue engineering and regenerative medicine, and particularly discloses a method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics, which comprises the following steps: transmitting ultrasonic pulses to a measurement area of the porous elastic scaffold, quickly tracking shear waves in the measurement area, and collecting real-time echo data; displacement of the porous elastic stent is obtained based on real-time echo data, and then inversion analysis is performed to obtain complex shear wave velocities at different sites in a measured area; determining a shear wave attenuation coefficient according to the complex shear wave speed and the shear wave excitation frequency; based on the shear wave attenuation coefficient, the porosity of the porous elastic stent in the current fluid-structure interaction state is determined, and the porosity is used for feeding back the degradation state of the porous elastic stent. According to the invention, non-invasive monitoring and dynamic evaluation are carried out on the physical structure state and the mechanical property of stent degradation, and quantitative, real-time and accurate monitoring can be carried out on the degradation process of the porous elastic stent in the biomedical field.

Description

Technical Field

[0001] The invention belongs to the technical field of tissue engineering and regenerative medicine, and in particular relates to a method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics. Background Art

[0002] In the field of biomedical engineering, porous elastic scaffolds play a vital role in tissue engineering and regenerative medicine. With the continuous advancement of science and technology, people's demand for tissue repair and regeneration is growing. As an important biomaterial, porous elastic scaffolds can provide space for cells to grow and proliferate, promoting tissue regeneration and repair. These scaffolds usually have good biocompatibility, degradability and certain mechanical strength, and can adapt to the complex environment in the body. However, accurately evaluating the degradation process of porous elastic scaffolds has always been a difficult problem that needs to be solved urgently.

[0003] At present, the technologies related to the propagation characteristics of shear waves are mainly concentrated in the fields of seismology and traditional medicine. There are few technologies related to the attenuation characteristics of shear waves and the degradation evaluation of bioelastic scaffold materials in tissue engineering and regenerative medicine. Shear waves are a type of elastic wave whose vibration direction is perpendicular to the propagation direction. When shear waves propagate in a medium, due to factors such as the internal friction and viscosity of the medium, the energy is gradually dissipated and the amplitude decreases. This phenomenon is called shear wave attenuation. Shear wave attenuation in solid media is greatly affected by the shear modulus and porosity of the medium. In anisotropic solid media, the attenuation degree of shear waves is different when propagating in different directions. By using shear wave elastic imaging technology and other techniques to transmit and receive shear wave signals and analyze the propagation speed and attenuation of shear waves in the medium, the structural and mechanical information of the material medium can be obtained.

[0004] At present, the commonly used methods for evaluating the degradation process of porous scaffolds mainly include traditional histological analysis, biochemical detection, imaging technology, etc. Histological analysis can provide more intuitive information, but it usually requires the implanted scaffold to be removed at a specific time point, sliced ​​and stained, and then the morphology and structural changes of the scaffold are observed under a microscope, which has certain limitations. What's more, it is a destructive detection method and cannot be monitored in real time. In addition, histological analysis requires a complex sample preparation process, the operation is cumbersome, and the results are highly subjective. Biochemical detection mainly evaluates the degradation of the scaffold by detecting specific biochemical indicators in the body, which can often only provide indirect information and cannot intuitively reflect the physical structural changes of the scaffold. For example, the concentration and enzyme activity of the degradation products of the scaffold are detected. The results of biochemical detection are also easily interfered by other factors, such as the metabolic state and inflammatory response in the body. Imaging technologies such as X-rays, CT, MRI, etc. are also used to evaluate the degradation of the scaffold. These technologies can provide non-invasive detection methods, but there are also some shortcomings. For example, the resolution of X-rays and CT for soft tissues is low, making it difficult to accurately evaluate the degradation of porous elastic scaffolds. Although MRI has a high resolution, its detection cost is high and it has high requirements for equipment and technology.

[0005] In summary, the currently used evaluation methods for the degradation process of porous elastic scaffolds have many limitations, such as the need for complex experimental equipment, cumbersome operations, inability to monitor in real time, inaccurate results, etc. These problems restrict the development and design of bioelastic scaffold materials in the field of tissue engineering and regenerative medicine. Therefore, a new and efficient evaluation method is urgently needed to accurately understand the degradation of porous elastic scaffolds. Summary of the invention

[0006] In view of the above-mentioned problems, the purpose of the present invention is to provide a method for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics, which can quantitatively, real-time and accurately monitor the degradation process of porous elastic scaffolds in the biomedical field, and the overall evaluation process is simple and efficient.

[0007] The technical solution of the present invention is: a method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics, comprising the following steps:

[0008] S1. Transmit ultrasonic pulses to the measuring area of ​​the porous elastic support, quickly track the shear waves in the measuring area and collect real-time echo data.

[0009] S2. The displacement of the porous elastic support is obtained based on the real-time echo data, and then an inversion analysis is performed to obtain the complex shear wave velocity at different locations in the measurement area.

[0010] S3. Determine the shear wave attenuation coefficient according to the complex shear wave velocity and the shear wave excitation frequency.

[0011] S4. Based on the shear wave attenuation coefficient, determine the porosity of the porous elastic support in the current fluid-solid coupling state, and the porosity is used to feedback the degradation state of the porous elastic support.

[0012] The shear wave attenuation coefficient β is determined according to the following formula.

[0013] Furthermore, the step S1 uses an ultrasonic transducer to emit ultrasonic pulses to the measurement area of ​​the porous elastic support.

[0014] Furthermore, the step S1 utilizes the same ultrasonic transducer to quickly track the shear wave in the measurement area and collect real-time echo data.

[0015] Furthermore, the shear wave is emitted by the ultrasonic transducer acting on the porous elastic support. Specifically, the acoustic radiation force of the ultrasonic transducer acting on the porous elastic support is focused axially at high speed at different depths of the measurement area, so that the particles in the measurement area vibrate and produce elastic deformation under the action of the acoustic radiation force. Accordingly, this elastic deformation is transmitted between the particles to generate a restoring force. Under the action of the restoring force, shear waves are excited in the measurement area.

[0016] Furthermore, the displacement of the porous elastic support described in step S2 is obtained specifically by: applying a phase shift estimation algorithm to track the micro-displacement of different sites in the imaging plane for inter-frame tissue movement, and obtaining the propagating shear wave displacement data of temporal and spatial variations, that is, obtaining the displacement of the porous elastic support.

[0017] Furthermore, in step S2, the complex shear wave velocity is determined according to the following formula:

[0018]

[0019] Where n represents the frame number, N represents the total number of frames, x, y represent the site positions of the measurement area, T represents the interval between two adjacent frames, and u represents the displacement of the porous elastic support.

[0020] Furthermore, the attenuation coefficient of the shear wave in step S3 is determined according to the following formula.

[0021] Where β represents the shear wave attenuation coefficient, ω represents the shear wave excitation frequency, and I m Represents the imaginary part of a complex number, V s represents the complex shear wave velocity, R e Represents the real part of a complex number.

[0022] Furthermore, the porosity of the porous elastic support in step S4 is determined according to the wave equation function relationship, and the wave equation function relationship is:

[0023]

[0024] in, ω represents the shear wave excitation frequency, represents the porosity of the porous elastic scaffold, X f represents the fluid compressibility, E represents the Young's modulus of the porous elastic support when the water is drained, G represents the shear modulus of the porous elastic support when the water is drained, u represents the displacement of the porous elastic support, ρ d represents the density of the porous elastic support when it is drained of water, ρ f represents the fluid density, p f represents the fluid pore pressure, ρ c (ω represents complex density, α B represents the Biot–Willis coefficient, represents the Hamiltonian operator, and i represents the imaginary unit of the complex number.

[0025] Compared with the prior art, the beneficial effect of the present invention is that the evaluation process of the present invention does not require complicated experimental equipment, and is based on the data foundation of "emitting ultrasonic pulses to the measurement area of ​​the porous elastic stent, quickly tracking the shear waves in the measurement area, and collecting real-time echo data", and both the emission of ultrasonic pulses and the collection of shear waves can be achieved by an ultrasonic transducer. The attenuation coefficient of the shear wave is calculated according to the complex shear wave velocity and the excitation frequency, and the porosity of the porous elastic stent is calculated by the shear wave attenuation coefficient to non-invasively monitor and dynamically evaluate the physical structure state and mechanical properties of the stent degradation, which can quantitatively, real-timely and accurately monitor the degradation process of the porous elastic stent in the biomedical field, and the overall evaluation process is simple and efficient.

[0026] The present invention is suitable for dynamic evaluation and non-invasive monitoring of the physical structure state and mechanical properties of biological porous scaffold materials in the field of tissue engineering and regenerative medicine during degradation, and the method minimizes the influence of boundary conditions, which is beneficial to the design and preparation of porous elastic scaffold materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 It is a work flow chart of the present invention;

[0028] Figure 2 , Figure 3 It is the vibration waveform simulation result of 300Hz shear wave propagation in the elastic support with a porosity of 0.4 in Experimental Example 1 of the present invention;

[0029] Figure 4 It is the comparison result of the relationship between the shear wave attenuation coefficient and the frequency obtained by the technical solution of the present invention and the amplitude attenuation fitting in the elastic support with a porosity of 0.4 in Experimental Example 1 of the present invention;

[0030] Figure 5It is the comparison result of Experimental Example 1 of the present invention between the technical solution of the present invention and the amplitude attenuation fitting to obtain the changing relationship between the shear wave propagation attenuation coefficient with a frequency of 300 Hz and the porosity of the elastic support. DETAILED DESCRIPTION

[0031] Combine the following Figures 1 to 5 , the specific implementation methods of the present invention are described in detail. In the description of the present invention, it should be understood that the terms "center", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention.

[0032] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features; in the description of the present invention, unless otherwise specified, "plurality" means two or more.

[0033] Example

[0034] like Figure 1 A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics is shown, comprising the following steps:

[0035] S1. Transmit ultrasonic pulses to the measuring area of ​​the porous elastic support, quickly track the shear waves in the measuring area and collect real-time echo data.

[0036] S2. The displacement of the porous elastic support is obtained based on the real-time echo data, and then an inversion analysis is performed to obtain the complex shear wave velocity at different locations in the measurement area.

[0037] S3. Determine the shear wave attenuation coefficient according to the complex shear wave velocity and the shear wave excitation frequency.

[0038] S4. Based on the shear wave attenuation coefficient, determine the porosity of the porous elastic support in the current fluid-solid coupling state, and the porosity is used to feedback the degradation state of the porous elastic support.

[0039] Preferably, step S1 uses an ultrasonic transducer to emit ultrasonic pulses to the measurement area of ​​the porous elastic support.

[0040] Preferably, step S1 uses the same ultrasonic transducer to quickly track the shear waves in the measurement area and collect real-time echo data.

[0041] It should be noted that: this embodiment uses an ultrasonic system to transmit ultrasonic pulses during the degradation process of the porous elastic scaffold, quickly track the shear wave and collect real-time echo data. The ultrasonic system includes an ultrasonic transducer, a multi-channel radio frequency transceiver module and a data processing module, wherein the multi-channel radio frequency transceiver module integrates multiple radio frequency channels, can simultaneously send and receive different data signal streams, and arranges the transceiver instructions in a logical order to ensure that the instructions run correctly. The data processing module is connected to the data acquisition storage control computer via PCle bus transmission.

[0042] Preferably, shear waves are emitted by an ultrasonic transducer acting on a porous elastic support. Specifically, the acoustic radiation force of the ultrasonic transducer acting on the porous elastic support is focused axially at high speed at different depths of the measurement area, so that the particles in the measurement area vibrate and produce elastic deformation under the action of the acoustic radiation force. Accordingly, this elastic deformation is transmitted between the particles to produce a restoring force, and under the action of the restoring force, shear waves are excited in the measurement area.

[0043] Preferably, the step S2 of acquiring the displacement of the porous elastic support is specifically as follows: for the inter-frame tissue movement, a phase shift estimation algorithm is applied to track the tiny displacements of different sites in the imaging plane, and the propagating shear wave displacement data of temporal and spatial variations are obtained, that is, the displacement of the porous elastic support is acquired.

[0044] Preferably, the complex shear wave velocity V in step S2 is s Determined according to the following formula.

[0045] Where n represents the frame number, N represents the total number of frames, x, y represent the site positions of the measurement area, T represents the interval between two adjacent frames, and u represents the displacement of the porous elastic support.

[0046] Preferably, the attenuation coefficient of the shear wave in step S3 is determined according to the following formula.

[0047] Where β represents the shear wave attenuation coefficient, ω represents the shear wave excitation frequency, and I m Represents the imaginary part of a complex number, V s represents the complex shear wave velocity, R e Represents the real part of a complex number.

[0048] Preferably, in step S4, the porosity of the porous elastic support is determined according to a wave equation function relationship, and the wave equation function relationship is:

[0049]

[0050] in, ω represents the shear wave excitation frequency, represents the porosity of the porous elastic scaffold, X frepresents the fluid compressibility, E represents the Young's modulus of the porous elastic support when the water is drained, G represents the shear modulus of the porous elastic support when the water is drained, u represents the displacement of the porous elastic support, ρ d represents the density of the porous elastic support when it is drained of water, ρ f represents the fluid density, p f represents the fluid pore pressure, ρ c (ω represents complex density, α B represents the Biot–Willis coefficient, represents the Hamiltonian operator, and i represents the imaginary unit of the complex number.

[0051] This embodiment effectively solves the problem of non-invasive monitoring of the state of porous elastic scaffolds in the field of tissue engineering and regenerative medicine as tissues grow and bioscaffolds degrade. Due to changes in the pore structure and shear wave attenuation characteristics of the porous elastic scaffold, the amplitude and phase of the echo data acquired by ultrasound change. By calculating the displacement and inversion analysis of the echo data, the complex shear wave velocity and attenuation coefficient can be obtained, and the porosity can be inferred from the attenuation coefficient to evaluate the degradation state of the scaffold. Among them, the greater the porosity of the porous elastic scaffold, the higher the degree of degradation of the porous elastic scaffold.

[0052] Experimental Example 1

[0053] The simulation experiment was carried out using the technical solution proposed in the embodiment, specifically:

[0054] The square 3D printed polysebacic acid glycerol porous scaffold is simulated to be completely immersed in physiological fluid to reach a saturated state, and a saturated porous elastic scaffold is obtained. By emitting ultrasonic pulses, shear waves are generated in the saturated porous elastic scaffold, and then the propagation of the shear waves is tracked and real-time echo signals are collected. Based on the echo signal, displacement acquisition and inversion analysis are performed to obtain the complex shear wave velocity at different locations in the test area, and the shear wave attenuation coefficient is calculated. Using the wave equation function relationship satisfied by the shear wave, the shear wave attenuation coefficient is input into the theoretical model, the porosity is solved, and the corresponding relationship change curve between the attenuation coefficient and the porosity of the elastic scaffold is plotted.

[0055] First, shear waves were generated at an excitation frequency of 300 Hz, and the variation of shear wave amplitude with propagation distance in an elastic support with a porosity of 0.4 was observed. Then, the effect of shear wave excitation at different frequencies on the shear wave propagation attenuation coefficient in an elastic support with a specific porosity, such as a porosity of 0.4, was studied. In addition, the relationship between the shear wave attenuation coefficient and the porosity of the elastic support was studied for a fixed shear wave excitation frequency, such as a shear wave excitation frequency of 300 Hz.

[0056] like Figure 2 , Figure 3As shown in Figure 1, the propagation amplitude of shear waves generated at an excitation frequency of 300 Hz in an elastic support with a porosity of 0.4 gradually decreases with the propagation distance. Figure 4 As shown, in an elastic support with a porosity of 0.4, the attenuation coefficient obtained by the technical solution proposed in the embodiment and the shear wave amplitude attenuation fitting both increase with increasing frequency and have good consistency. Figure 5 As shown, when the shear wave excitation frequency is 300 Hz, in elastic supports with different porosities, the attenuation coefficient obtained by fitting the technical solution proposed in the embodiment and the shear wave amplitude has good consistency when the porosity is lower than 0.5.

[0057] It should be noted that this experimental example is a simulation experimental example, which uses the wave equation function relationship satisfied by the shear wave, inputs the shear wave attenuation coefficient into the theoretical model, solves the porosity, and compares and analyzes the results at different times to further understand the changes in the pore structure during the degradation of the stent, and then feedback the degradation status of the stent.

[0058] Experimental Example 2

[0059] The difference between the simulation experiment example and the experiment example 1 is that when the experiment example is performed using the embodiment, the porous elastic scaffold needs to be immersed in the simulated physiological fluid to fully saturate it, obtain the saturated porous elastic scaffold, and then measure the saturated porous elastic scaffold. In addition, the saturated porous elastic scaffold needs to be repeatedly measured within a period of time to obtain the shear wave propagation attenuation coefficient at different time points. Specifically:

[0060] Biodegradable polymer materials are used to prepare porous elastic scaffolds with certain pore structures and shapes through specific molding processes. Specifically, poly 1,8-octanediol-citric acid is used to prepare porous elastic scaffolds with certain pore structures and shapes through 3D printing, freeze drying and other processes.

[0061] The porous elastic scaffold is immersed in a simulated physiological fluid to fully saturate the porous elastic scaffold to obtain a saturated porous elastic scaffold. The simulated physiological fluid is specifically selected from a phosphate buffer solution, 37°C PBS, PH=7.4.

[0062] By emitting ultrasonic pulses, shear waves are generated in the saturated porous elastic support, and then the propagation of shear waves is tracked by ultrasonic transducers to collect real-time echo signals. The sampling frequency is set to a high value, specifically 10MHz, to ensure data accuracy and measurement precision. Based on the echo signal, displacement acquisition and inversion analysis are performed to obtain the complex shear wave velocity at different locations in the test area and calculate the shear wave attenuation coefficient.

[0063] The saturated porous elastic scaffold is placed in an incubator simulating a physiological environment, taken out at certain time intervals, such as 14 days, 28 days, 42 days, etc., and measured again using an ultrasonic transducer system to obtain the shear wave propagation attenuation coefficient at different time points.

[0064] As the saturated porous elastic scaffold degrades, its internal structure changes, the porosity increases, the material density decreases, etc., which leads to a gradual increase in the attenuation coefficient of the shear wave and an enhancement in the dissipation effect of the saturated porous elastic scaffold material on the shear wave.

[0065] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and does not limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention are included in the protection scope of the present invention.

Claims

1. A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics, characterized in that: The following steps are involved: S1, transmitting ultrasonic pulses to the measurement area of ​​the porous elastic support, quickly tracking the shear waves in the measurement area and collecting real-time echo data; S2, obtaining the displacement of the porous elastic support based on the real-time echo data, and then performing inversion analysis to obtain the complex shear wave velocity at different locations in the measurement area; S3, determining the shear wave attenuation coefficient according to the complex shear wave velocity and the shear wave excitation frequency; S4. Based on the shear wave attenuation coefficient, determine the porosity of the porous elastic support in the current fluid-solid coupling state, and the porosity is used to feedback the degradation state of the porous elastic support.

2. A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 1, characterized in that: The step S1 uses an ultrasonic transducer to transmit ultrasonic pulses to the measurement area of ​​the porous elastic support.

3. A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 2, characterized in that: The step S1 uses the same ultrasonic transducer to quickly track the shear wave in the measurement area and collect real-time echo data.

4. A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 3, characterized in that: The shear wave is emitted by the ultrasonic transducer acting on the porous elastic support. Specifically, the acoustic radiation force of the ultrasonic transducer acting on the porous elastic support is focused at high speed along the axial direction at different depths of the measurement area, so that the particles in the measurement area vibrate and produce elastic deformation under the action of the acoustic radiation force. Correspondingly, this elastic deformation is transmitted between the particles to generate a restoring force. Under the action of the restoring force, shear waves are excited in the measurement area.

5. The method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 1, characterized in that: The acquisition of the displacement of the porous elastic support in step S2 is specifically as follows: for the inter-frame tissue movement, a phase shift estimation algorithm is applied to track the tiny displacements of different sites in the imaging plane, and the propagation shear wave displacement data of temporal and spatial variations are obtained, that is, the displacement of the porous elastic support is obtained.

6. A method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 5, characterized in that: The complex shear wave velocity in step S2 is determined according to the following formula: Where n represents the frame number, N represents the total number of frames, x, y represent the site positions of the measurement area, T represents the interval between two adjacent frames, and u represents the displacement of the porous elastic support.

7. The method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 1, characterized in that: The attenuation coefficient of the shear wave in step S3 is determined according to the following formula: Where β represents the shear wave attenuation coefficient, ω represents the shear wave excitation frequency, and I m Represents the imaginary part of a complex number, V s represents the complex shear wave velocity, R e Represents the real part of a complex number.

8. The method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics according to claim 1, characterized in that: The porosity of the porous elastic support in step S4 is determined according to the wave equation function relationship, and the wave equation function relationship is: in, ω represents the shear wave excitation frequency, represents the porosity of the porous elastic scaffold, X f represents the fluid compressibility, E represents the Young's modulus of the porous elastic support when the water is drained, G represents the shear modulus of the porous elastic support when the water is drained, u represents the displacement of the porous elastic support, ρ d represents the density of the porous elastic support when it is drained of water, ρ f represents the fluid density, p f represents the fluid pore pressure, ρ c( ω ) represents the complex density, α B represents the Biot–Willis coefficient, represents the Hamiltonian operator, and i represents the imaginary unit of the complex number.

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