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

Abstract

The present application belongs to the technical field of tissue engineering and regenerative medicine, and specifically discloses a method for evaluating the degradation process of a porous elastic scaffold based on shear wave attenuation characteristics, comprising the following steps: emitting an ultrasonic pulse to a measurement area of the porous elastic scaffold, rapidly tracking the shear wave in the measurement area and collecting real-time echo data; obtaining the displacement of the porous elastic scaffold based on the real-time echo data, then performing inversion analysis to obtain the complex shear wave velocity at different sites in the measurement area; determining the shear wave attenuation coefficient according to the complex shear wave velocity and the shear wave excitation frequency; and determining the current fluid-solid coupling state porous elastic scaffold porosity based on the shear wave attenuation coefficient, wherein the porosity is used to feedback the degradation state of the porous elastic scaffold. The present application non-invasively monitors and dynamically evaluates the physical structure state and mechanical properties of the scaffold degradation, and can quantitatively, real-timely and accurately monitor the degradation process of the porous elastic scaffold in the biomedical field.

Description

Technical Field

[0001] This invention belongs to the field of tissue engineering and regenerative medicine technology, and specifically relates to a method for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics. Background Technology

[0002] In the field of biomedical engineering, porous elastic scaffolds play a crucial role in tissue engineering and regenerative medicine. With continuous technological advancements, the demand for tissue repair and regeneration is increasing. As an important biomaterial, porous elastic scaffolds provide space for cell growth and proliferation, promoting tissue regeneration and repair. These scaffolds typically possess good biocompatibility, biodegradability, and a certain degree of mechanical strength, enabling them to adapt to the complex environment within the body. However, accurately assessing the degradation process of porous elastic scaffolds remains a challenging problem to be solved.

[0003] Currently, technologies related to shear wave propagation characteristics are mainly concentrated in seismology and traditional medicine, with few technologies addressing the degradation evaluation of shear wave attenuation characteristics and bio-elastic scaffold materials in tissue engineering and regenerative medicine. A shear wave is an elastic wave whose vibration direction is perpendicular to its propagation direction. When a shear wave propagates in a medium, its energy gradually dissipates and its amplitude decreases due to factors such as internal friction and viscosity; this phenomenon is called shear wave attenuation. Shear wave attenuation in solid media is greatly affected by factors such as the medium's shear modulus and porosity. In anisotropic solid media, the degree of attenuation varies depending on the direction of propagation. By using shear wave elastography and other techniques to transmit and receive shear wave signals, and analyzing the propagation speed and attenuation of shear waves in a medium, structural and mechanical information about the material can be obtained.

[0004] Currently, commonly used methods for assessing the degradation process of porous scaffolds mainly include traditional histological analysis, biochemical testing, and imaging techniques. Histological analysis provides relatively intuitive information, but it typically requires removing the implanted scaffold at specific time points, sectioning and staining it, and then observing the morphological and structural changes of the scaffold under a microscope, which has certain limitations. Moreover, it is a destructive testing method and cannot provide real-time monitoring. Furthermore, histological analysis requires complex sample preparation processes, is cumbersome, and the results are highly subjective. Biochemical testing mainly assesses scaffold degradation by detecting specific biochemical indicators in the organism, often providing only indirect information and not directly reflecting changes in the physical structure of the scaffold. For example, it detects the concentration of scaffold degradation products and enzyme activity. The results of biochemical testing are also easily affected by other factors, such as the metabolic state and inflammatory response in the organism. Imaging techniques such as X-rays, CT, and MRI are also used to assess scaffold degradation. These techniques provide non-invasive detection methods, but they also have some shortcomings. For example, X-rays and CT have low resolution for soft tissues, making it difficult to accurately assess the degradation of porous elastic scaffolds. Although MRI has high resolution, it is expensive to perform and requires advanced equipment and technology.

[0005] In summary, current methods for assessing the degradation process of porous elastic scaffolds have many limitations, such as requiring complex experimental equipment, cumbersome operation, inability to monitor in real time, and inaccurate results. These problems hinder the development and design of bio-elastic scaffold materials in the fields of tissue engineering and regenerative medicine. Therefore, there is an urgent need for a new and efficient assessment method to accurately understand the degradation status of porous elastic scaffolds. Summary of the Invention

[0006] To address the aforementioned problems, the purpose of this invention is to provide a method for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics. This method can quantitatively, in 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 this invention is: a method for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics, comprising the following steps:

[0008] S1. An ultrasonic pulse is emitted into the measurement area of ​​the porous elastic support to quickly track the shear wave within the measurement area and collect real-time echo data.

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

[0010] S3. Determine the shear wave attenuation coefficient based on 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 under the current fluid-structure interaction state. The porosity is used to provide feedback on the degradation state of the porous elastic support.

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

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

[0014] Furthermore, step S1 utilizes the same ultrasonic transducer to rapidly track shear waves within the measurement area and acquire real-time echo data.

[0015] Furthermore, the shear wave is 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 at high speed along the axis at different depths of the measurement area, thereby causing the particles in the measurement area to 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, a shear wave is excited in the measurement area.

[0016] Further, the acquisition of the displacement of the porous elastic scaffold in step S2 is specifically as follows: for inter-frame tissue motion, a phase shift estimation algorithm is applied to track the minute displacements of different sites in the imaging plane to obtain propagating shear wave displacement data that varies in time and space, that is, to obtain the displacement of the porous elastic scaffold.

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

[0018]

[0019] Where n represents the frame number, N represents the total number of frames, x and y represent the location of the site in the measurement area, T represents the time 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 V represents the imaginary part of a complex number. s R represents the complex shear wave velocity. e Represents the real part of a complex number.

[0022] Furthermore, the porosity of the porous elastic support described in step S4 is determined based on the wave equation functional relationship, which is:

[0023]

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

[0025] Compared with existing technologies, the advantages of this invention are as follows: The evaluation process of this invention does not require complex experimental equipment. Based on the data foundation of "emitting ultrasonic pulses to the measurement area of ​​a porous elastic scaffold and rapidly tracking and collecting real-time echo data of the shear waves within the measurement area," both the emission of ultrasonic pulses and the acquisition of shear waves can be achieved through an ultrasonic transducer. The attenuation coefficient of the shear wave is calculated based on the complex shear wave velocity and excitation frequency. This attenuation coefficient is then used to calculate the porosity of the porous elastic scaffold, enabling non-invasive monitoring and dynamic evaluation of the physical structural state and mechanical properties of the scaffold degradation. This allows for quantitative, real-time, and accurate monitoring of the degradation process of porous elastic scaffolds in the biomedical field, and the overall evaluation process is simple and efficient.

[0026] This invention is applicable to the dynamic evaluation and non-invasive monitoring of the physical structure and mechanical properties of porous bio-scaffold materials in the fields of tissue engineering and regenerative medicine during the degradation process. Furthermore, this method minimizes the influence of boundary conditions, which is beneficial for the design and preparation of porous elastic scaffold materials. Attached Figure Description

[0027] Figure 1 This is a flowchart of the process of this invention;

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

[0029] Figure 4 This is a comparison of the relationship between the technical solution of this invention and the shear wave attenuation coefficient and frequency obtained by amplitude attenuation fitting in an elastic support with a porosity of 0.4 in Experiment Example 1 of this invention.

[0030] Figure 5This is the comparison result of Experiment Example 1 of the present invention, which shows the relationship between the shear wave propagation attenuation coefficient at a frequency of 300Hz and the porosity of the elastic support obtained by fitting the technical solution of the present invention with the amplitude attenuation. Detailed Implementation

[0031] The following is combined Figures 1 to 5 The specific embodiments of the present invention will be described in detail below. In the description of the present invention, it should be understood that the terms "center," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings and are only for the convenience of describing the present invention and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention.

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

[0033] Example

[0034] like Figure 1 The method shown here for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics includes the following steps:

[0035] S1. An ultrasonic pulse is emitted into the measurement area of ​​the porous elastic support to quickly track the shear wave within the measurement area and collect real-time echo data.

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

[0037] S3. Determine the shear wave attenuation coefficient based on 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 under the current fluid-structure interaction state. The porosity is used to provide feedback on the degradation state of the porous elastic support.

[0039] Preferably, in step S1, an ultrasonic transducer is used to emit ultrasonic pulses toward the measurement area of ​​the porous elastic scaffold.

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

[0041] It should be noted that this embodiment uses an ultrasonic system to emit ultrasonic pulses during the degradation process of the porous elastic scaffold and to rapidly track and acquire real-time echo data of the shear waves. The ultrasonic system includes an ultrasonic transducer, a multi-channel RF transceiver module, and a data processing module. The multi-channel RF transceiver module integrates multiple RF channels, enabling simultaneous transmission and reception of different data signal streams. It arranges the transmission and reception commands in a logical order to ensure correct command execution. The data processing module is connected to the data acquisition, storage, and control computer via a PCIe bus.

[0042] Preferably, 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 axis to 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, a shear wave is excited in the measurement area.

[0043] Preferably, step S2, obtaining the displacement of the porous elastic scaffold, specifically involves: applying a phase shift estimation algorithm to track the minute displacements at different points within the imaging plane for inter-frame tissue motion, thereby obtaining temporal and spatially varying propagating shear wave displacement data, which is how the displacement of the porous elastic scaffold is obtained.

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

[0045] Where n represents the frame number, N represents the total number of frames, x and y represent the location of the site in the measurement area, T represents the time 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 V represents the imaginary part of a complex number. s R represents the complex shear wave velocity. e Represents the real part of a complex number.

[0048] Preferably, in step S4, the porosity of the porous elastic support is determined based on the wave equation functional relationship, which is:

[0049]

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

[0051] This embodiment effectively addresses the challenge of non-invasive monitoring of the status of porous elastic scaffolds during tissue growth and bioscaffold degradation in tissue engineering and regenerative medicine. Changes in the pore structure and shear wave attenuation characteristics of the porous elastic scaffold lead to variations in the amplitude and phase of the ultrasound-acquired echo data. By calculating displacement and performing inversion analysis using the echo data, the complex shear wave velocity and attenuation coefficient can be obtained. The porosity can then be inferred from the attenuation coefficient to evaluate the scaffold degradation status. A higher porosity indicates a greater degree of degradation in the porous elastic scaffold.

[0052] Experimental Example 1

[0053] The simulation experiment was conducted using the technical solution proposed in the embodiments, specifically as follows:

[0054] A 3D-printed polyglycerol sebate porous scaffold, simulating a square shape, was fully immersed in physiological fluid to achieve saturation, resulting in a saturated porous elastic scaffold. Shear waves were generated within the saturated porous elastic scaffold by emitting ultrasonic pulses. The propagation of the shear waves was then tracked, and real-time echo signals were acquired. Based on the echo signals, displacement acquisition and inversion analysis were performed to obtain the complex shear wave velocity at different locations within the test area, and the shear wave attenuation coefficient was calculated. Using the wave equation function satisfied by the shear wave, the shear wave attenuation coefficient was input into a theoretical model to solve for the porosity, and the curves showing the relationship between the attenuation coefficient and the porosity of the elastic scaffold were plotted.

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

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

[0057] It should be noted that this experimental example is a simulation experiment. It utilizes the wave equation function relationship satisfied by shear waves, 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 pore structure during stent degradation, and thus provide feedback on the stent degradation status.

[0058] Experimental Example 2

[0059] Unlike the simulated experiment in Example 1, the experimental example using this embodiment requires immersing the porous elastic scaffold in simulated physiological fluid until it is fully saturated, resulting in a saturated porous elastic scaffold. Measurements are then taken of the saturated porous elastic scaffold. Furthermore, the saturated porous elastic scaffold needs to be repeatedly measured over a period of time to obtain the shear wave propagation attenuation coefficient at different time points. Specifically:

[0060] Porous elastic scaffolds with specific pore structures and shapes are prepared using biodegradable polymer materials through a specific molding process. Specifically, poly(1,8-octanediol-citric acid) is used to prepare porous elastic scaffolds with specific pore structures and shapes through processes such as 3D printing and freeze-drying.

[0061] The porous elastic scaffold was immersed in simulated physiological fluid until it was fully saturated, resulting in a saturated porous elastic scaffold. The simulated physiological fluid was specifically phosphate-buffered saline (PBS) at 37°C with a pH of 7.4.

[0062] Shear waves are generated in a saturated porous elastic scaffold by emitting ultrasonic pulses. An ultrasonic transducer is then used to track the propagation of these shear waves, acquiring real-time echo signals. The sampling frequency is set to a relatively high value, such as 10MHz, to ensure data accuracy and measurement precision. Based on the echo signals, displacement acquisition and inversion analysis are performed to obtain the complex shear wave velocity at different locations within the measured area, and the shear wave attenuation coefficient is calculated.

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

[0064] As saturated porous elastic scaffolds degrade, their internal structure changes, such as increased porosity and decreased material density, which leads to a gradual increase in the attenuation coefficient of shear waves and enhances the dissipation effect of saturated porous elastic scaffold materials on shear waves.

[0065] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and do not limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention are included within the protection scope of the present invention.

Claims

1. A method for evaluating the degradation process of porous elastic scaffolds based on shear wave attenuation characteristics, characterized in that, Includes the following steps: S1. Emit ultrasonic pulses to the measurement area of ​​the porous elastic support to quickly track the shear waves in the measurement area and collect real-time echo data. S2. The displacement of the porous elastic support is obtained based on real-time echo data, and then the complex shear wave velocity at different points in the measurement area is obtained by inversion analysis. S3. Determine the shear wave attenuation coefficient based on 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 under the current fluid-structure interaction state. The porosity is used to provide feedback on the degradation state of the porous elastic support. In step S1, an ultrasonic transducer is used to emit ultrasonic pulses toward the measurement area of ​​the porous elastic support. Step S1 involves using the same ultrasonic transducer to rapidly track shear waves within the measurement area and collect real-time echo data. The shear waves are 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 within the measurement area, causing the particles in the measurement area to vibrate and undergo 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 within the measurement area. 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, I represents the excitation frequency of the shear wave. m V represents the imaginary part of a complex number. s express Complex shear wave velocity, R e Represents the real part of a complex number; Step S4: The porosity of the porous elastic support is determined based on the wave equation function, which is as follows: ； ； in, , The shear wave excitation frequency is represented by φ, the porosity of the porous elastic scaffold is represented by X. f Let E represent the fluid compressibility coefficient, E represent the Young's modulus of the porous elastic support when drained of water, G represent the shear modulus of the porous elastic support when drained of water, and u represent the displacement of the porous elastic support. This indicates the density of the porous elastic support when it is drained of water. P represents fluid density. f Indicates fluid pore pressure, Denotes the complex density, α B denoted by Biot-Willis coefficient, ▽ denotes the Hamiltonian operator, and i denotes the imaginary unit of the complex number; The specific steps for obtaining the displacement of the porous elastic scaffold in step S2 are as follows: for inter-frame tissue motion, a phase shift estimation algorithm is applied to track the minute displacements at different points in the imaging plane to obtain temporal and spatially varying propagating shear wave displacement data, that is, to obtain the displacement of the porous elastic scaffold. 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 and y represent the location of the site in the measurement area, T represents the time interval between two adjacent frames, and u represents the displacement of the porous elastic support.

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