Biological scaffold viscoelasticity evaluation method and related equipment

Abstract

The invention discloses a biological scaffold viscoelasticity evaluation method and related equipment, and aims to overcome the defects of an existing biological scaffold viscoelasticity test method and biological tissue suitability quantitative evaluation. The method comprises the following steps: determining a target implantation part, and acquiring force relaxation experimental data of a biological scaffold by using an atomic force microscope; judging a contact point of the probe and the bracket based on the data; determining the moment when the force signal is stable after the support is compressed to the preset deformation according to the contact point as a force relaxation starting point; calculating the characteristic time when the force value is attenuated to half by taking the starting point as a timing starting point as a microscopic viscoelasticity index; and finally, realizing quantitative evaluation of viscoelasticity suitability by comparing the characteristic time of the stent and the target tissue.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological scaffolds, in particular to a biological scaffold viscoelasticity evaluation method and related equipment. BACKGROUND

[0002] Tissue engineering aims to construct functional tissue substitutes to repair damaged organs, in which the mechanical properties of biological scaffolds, especially viscoelasticity, have been proven to be key factors in regulating cell behavior, tissue development and ultimately therapeutic effect. Cells perceive the viscoelasticity (such as stress relaxation, creep) of the scaffold through structures such as integrin focal adhesion, and then trigger related signaling pathways to directly regulate stem cell differentiation direction. Natural tissues (such as cartilage, myocardium, blood vessels) generally exhibit significant viscoelastic behavior, and if the scaffold only simulates static modulus and ignores dynamic viscoelasticity, it will lead to mechanical mismatch, causing inflammatory reaction or implant failure. Studies have shown that more than 70% of scaffold implantation failures are due to insufficient mechanical properties.

[0003] Although the existing test method based on a rheometer can quantify the macroscopic viscoelasticity of the material, the probe size is millimeter level, which cannot characterize the local viscoelasticity difference dominated by the internal microstructure (such as pores, fiber nodes) of the scaffold, and the test frequency range is limited, which is difficult to cover the ultra-low frequency and high frequency impact in physiological activities. In addition, although the atomic force microscope can perform micro-nano scale characterization, it lacks a standardized experiment and data analysis system, resulting in poor data comparability, difficulty in model construction, and inability to effectively correlate the mechanical microenvironment perceived by cells at the subcellular scale, causing the contradiction of "macroscopic matching, microscopic mismatch". Therefore, it is urgent to establish a method that can accurately test the micro viscoelasticity of biological scaffolds and realize quantitative comparison and evaluation with target tissues, in order to guide the mechanical adaptability design and optimization of scaffolds and improve the success rate of implantation. SUMMARY

[0004] The purpose of the present application is to provide a biological scaffold viscoelasticity evaluation method and related equipment to overcome the deficiencies of the existing biological scaffold viscoelasticity test method and biological tissue adaptability quantitative evaluation.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: In a first aspect, the present application provides a biological scaffold viscoelasticity evaluation method, comprising: determining a target implantation site, testing a biological scaffold using an atomic force microscope, and obtaining force relaxation experimental data of the biological scaffold; judging the force relaxation curve contact point of the atomic force microscope probe and the biological scaffold according to the force relaxation experimental data; According to the contact point of the force relaxation curve of the atomic force microscope probe and the biological scaffold, the time when the force signal of the biological scaffold is stable after being compressed to the preset deformation amount is determined as the starting point of force relaxation; Taking the starting point of force relaxation as the timing starting point, the characteristic time corresponding to the time when the force value decays to half of the starting point force value is calculated as the micro-viscoelasticity characteristic index of the biological scaffold; The characteristic time of the biological scaffold is compared with the micro-viscoelasticity characteristic index of the target implantation tissue site to obtain the viscoelasticity evaluation result of the biological scaffold.

[0006] Determine the target implantation site, use the atomic force microscope to test the biological scaffold, and obtain the force relaxation experimental data of the biological scaffold, including: The atomic force microscope uses a spherical probe with a diameter of 15-25 microns to approach the biological scaffold at a speed of 15-25 μm / s; After the probe contacts the biological scaffold, continue to compress to a preset deformation amount of the biological scaffold; Keep the preset deformation amount constant, analyze the deflection change of the cantilever beam of the atomic force microscope probe over time, calculate the force relaxation process of the biological scaffold, and obtain the force relaxation experimental data of the biological scaffold.

[0007] According to the force relaxation experimental data, the contact point of the force relaxation curve of the atomic force microscope probe and the biological scaffold is determined, including: The force F-displacement Z curve is included in the force relaxation experimental data, and the inflection point where the value of dF / dZ starts to increase stably from zero is identified by derivative calculation on the force F-displacement Z curve; Based on the noise level of the experimental environment, a force threshold is set to identify the displacement position where the force value first exceeds the force threshold continuously in the force F-displacement Z curve; The contact point is determined comprehensively in combination with the inflection point and the displacement position.

[0008] The time when the force signal of the biological scaffold is stable after being compressed to the preset deformation amount is determined as the starting point of force relaxation, including: Identify the force surge node generated when the atomic force microscope probe reaches the preset deformation amount; Select the time corresponding to 200-300 sampling points from the force surge node as the time when the force signal is stable.

[0009] The characteristic time corresponding to the time when the force value decays to half of the starting point force value is calculated, including: The force relaxation experimental data includes the force relaxation-time curve, and the ratio of the force F(t) at each time to the force F0 at the starting point of force relaxation is calculated by normalizing the force relaxation-time curve; Identify the time point when the ratio first reaches 0.5, and calculate the time difference between the time point and the starting point of force relaxation as the characteristic time.

[0010] The pre-processing of the force relaxation-time curve before normalization of the force relaxation curve includes: The starting point of force relaxation is repeatedly selected and a smoothing algorithm is used on the force relaxation-time curve until the force relaxation-time curve is stable.

[0011] The characteristic time of the biological scaffold is compared with the micro-viscoelasticity characteristic index of the target implantation tissue site, including: A plurality of characteristic time measurement values of the biological scaffold and the target implantation tissue site are obtained respectively to form a characteristic time distribution; Based on the characteristic time distribution, the true positive rate and the false positive rate under different judgment thresholds are calculated; The working characteristic curve of the biological scaffold and the target value such as tissue is drawn to obtain the viscoelasticity evaluation result of the biological scaffold.

[0012] In a second aspect, the present application provides a biological scaffold viscoelasticity evaluation system, comprising: A data acquisition module is configured to determine a target implantation site, test a biological scaffold using an atomic force microscope, and obtain force relaxation experimental data of the biological scaffold; A contact point calculation module is configured to determine the contact point of the atomic force microscope probe and the force relaxation curve of the biological scaffold based on the force relaxation experimental data; A starting point calculation module is configured to determine the time when the force signal is stable after the biological scaffold is compressed to a preset deformation amount as the starting point of force relaxation based on the contact point of the atomic force microscope probe and the force relaxation curve of the biological scaffold; A characteristic time calculation module is configured to calculate the characteristic time corresponding to the time when the force value decays to half of the starting point force value as the micro-viscoelasticity characteristic index of the biological scaffold with the starting point of force relaxation as the timing starting point; An evaluation module is configured to compare the characteristic time of the biological scaffold with the micro-viscoelasticity characteristic index of the target implantation tissue site to obtain the viscoelasticity evaluation result of the biological scaffold.

[0013] In a third aspect, the present application provides a computer device, comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, wherein the processor executes the computer program to implement the steps of the biological scaffold viscoelasticity evaluation method as described above.

[0014] In a fourth aspect, the present application provides a computer readable storage medium, wherein the computer readable storage medium stores a computer program, and the computer program is executed by a processor to implement the steps of the biological scaffold viscoelasticity evaluation method as described above.

[0015] Compared with the prior art, the present application has the following beneficial technical effects: Firstly, this invention provides a viscoelasticity assessment method for biological scaffolds. By employing atomic force microscopy to perform micro / nanoscale testing on the biological scaffolds, force relaxation experimental data reflecting their internal microstructure are directly obtained, overcoming the spatial resolution limitations of traditional rheometer testing. By accurately determining the contact point and start point of the force relaxation curve, a reliable viscoelastic analysis benchmark is established, ensuring the accuracy of characteristic time parameter calculations. Directly comparing the characteristic times of the biological scaffold with corresponding indicators of the target implanted tissue achieves a quantitative assessment of mechanical adaptability at the cellular sensing scale, solving the problems of scale mismatch and lack of unified assessment standards in traditional methods.

[0016] Secondly, this invention provides a viscoelasticity evaluation system for biological scaffolds. The data acquisition module uses atomic force microscopy for testing, ensuring the acquisition of mechanical data of the biological scaffold at the microscopic scale and overcoming the shortcomings of insufficient spatial resolution in traditional rheometers. The contact point calculation module and the start point calculation module establish a reliable mechanical analysis benchmark through precise algorithmic judgment, eliminating interference from human factors and instrument noise. The characteristic time calculation module quantifies the complex viscoelastic behavior into a single characteristic time parameter, achieving standardized characterization of material properties. The evaluation module establishes an objective quantitative evaluation system by directly comparing the characteristic time of the biological scaffold with the corresponding parameters of the target tissue. A complete technical closed loop is formed among the modules: the data acquisition module provides raw data for subsequent analysis; the contact point calculation module and the start point calculation module ensure the accuracy of the analysis benchmark; the characteristic time calculation module realizes parameter transformation; and finally, the evaluation module completes the suitability judgment.

[0017] Thirdly, the present invention provides a computer device that, through a processor executing a specific computer program, can efficiently implement the steps of the method of the present invention. When performing data processing tasks, the computer device can accurately perform numerical calculations and logical judgments, avoiding errors caused by human factors. At the same time, since the computer program has high stability and reliability, it can ensure the accuracy and consistency of the data processing results.

[0018] Fourthly, the present invention provides a computer-readable storage medium. By programming the steps of the method of the present invention into a computer program and storing it on the computer-readable storage medium, users can easily load these programs onto any compatible computer device and execute them without rewriting or converting the code, which greatly improves the convenience and flexibility of program execution. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of a method for evaluating the viscoelasticity of a biological scaffold in an embodiment of the present invention.

[0020] Figure 2A force-displacement curve diagram of force relaxation experiment data in an embodiment of the present application.

[0021] Figure 3 A force-time curve diagram of force relaxation experiment data in an embodiment of the present application.

[0022] Figure 4 A normalized processing result diagram of force relaxation-time curve in an embodiment of the present application.

[0023] Figure 5 An existing bio-scaffold viscoelasticity evaluation schematic diagram.

[0024] Figure 6 A bio-scaffold viscoelasticity evaluation schematic diagram in an embodiment of the present application.

[0025] Figure 7 A bio-scaffold viscoelasticity evaluation system schematic diagram in an embodiment of the present application. DETAILED DESCRIPTION

[0026] Tissue engineering aims to construct functional tissue substitutes to repair damaged organs. As a cell carrier, the viscoelasticity of a bio-scaffold is a key factor in regulating cell behavior and treatment effect. Cells perceive the viscoelasticity of the scaffold through integrin focal adhesion, and then regulate stem cell differentiation. Natural tissues have significant viscoelasticity, and if the scaffold only simulates the static modulus, it will lead to mechanical mismatch, and research shows that more than 70% of implantation failures are due to insufficient mechanical properties.

[0027] Although the existing rheometer test can obtain macroscopic viscoelasticity data, its millimeter-level probe cannot characterize the local differences of the internal microstructure of the scaffold, and the test frequency range is also difficult to cover the full spectrum of physiological activities. Although atomic force microscopy can realize micro-nano scale characterization, it lacks a standardized experiment and data analysis system, resulting in poor data comparability, and cannot effectively correlate the microenvironment perceived by cells, causing the contradiction of "macroscopic matching, microscopic mismatch".

[0028] The present application provides a bio-scaffold viscoelasticity evaluation method and related equipment, which directly obtains micro force relaxation data of the bio-scaffold by using an atomic force microscope, determines the contact point and the relaxation starting point, extracts characteristic time parameters representing viscoelasticity, and realizes direct quantitative comparison of the mechanical properties of the scaffold and the target tissue on a micro scale. This scheme effectively solves the scale mismatch problem existing in traditional methods, establishes a unified quantitative evaluation standard, and provides a reliable basis for scaffold design and optimization.

[0029] With reference to the drawings of the embodiments of the present application, the technical solutions in the embodiments of the present application will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of the present application.

[0030] With reference to Figure 1 As shown in FIG. 1, the method for evaluating the viscoelasticity of a biological stent provided by the present application includes the following steps. The method for evaluating the viscoelasticity of a biological stent includes the following steps. Determine a target implantation site, test the biological stent using an atomic force microscope, and obtain force relaxation experimental data of the biological stent; According to the force relaxation experimental data, determine the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent; According to the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent, determine the time point at which the force signal of the biological stent is stable after being compressed to a preset deformation amount, as the starting point of force relaxation; Take the starting point of force relaxation as the starting point of timing, calculate the characteristic time corresponding to the time when the force value decays to half of the starting point force value, as the micro-viscoelasticity characteristic index of the biological stent; Compare the characteristic time of the biological stent with the micro-viscoelasticity characteristic index of the target implantation tissue site, and obtain the evaluation result of the viscoelasticity of the biological stent.

[0031] In the present embodiment, the determination of the target implantation site establishes the biological benchmark for the mechanical adaptability evaluation, providing the necessary reference standard for subsequent comparison and analysis. The use of the atomic force microscope to test the biological stent takes advantage of the instrument's advantages in micro-nano scale mechanical testing, and its high-resolution detection capability lays a foundation for obtaining accurate force relaxation experimental data.

[0032] According to the force relaxation experimental data, the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent is determined, which establishes an accurate starting benchmark for mechanical measurement and eliminates the influence of long-range forces and instrument noise on the test results. Based on the determined contact point, the time point at which the force signal of the biological stent is stable after being compressed to a preset deformation amount is determined as the starting point of force relaxation, which ensures the accuracy and reliability of the time starting point of viscoelasticity analysis and eliminates transient disturbances such as impact effect.

[0033] The force value decay to half of the starting point force value is calculated as a characteristic time, which is used as a micro-viscoelasticity characteristic index of the biological scaffold. The complex viscoelastic behavior is quantified as a single characteristic parameter, which is convenient for subsequent comparative analysis. The characteristic time of the biological scaffold is compared with the micro-viscoelasticity characteristic index of the target tissue implant site, and the mechanical adaptability of the biological scaffold and the target tissue at the microscale is evaluated through direct parameter comparison.

[0034] The steps are closely related in technology and function: accurate contact point determination provides a basis for determining the starting point of force relaxation, accurate starting point positioning ensures the reliability of characteristic time calculation, and the characteristic time, as a quantitative parameter, provides a unified standard for the final adaptability comparison, which together constitutes a complete micro-viscoelasticity evaluation technical scheme.

[0035] In another specific embodiment of the biological scaffold viscoelasticity evaluation method provided by the application, an active biological scaffold for repairing mouse spinal cord injury is selected, and the mouse spinal cord tissue is determined as the target tissue implant site. Whether the biological scaffold matches the mechanical microenvironment of the target implant site is evaluated by comparing the micro-viscoelasticity characteristics of the biological scaffold and the spinal cord tissue.

[0036] In this specific embodiment, the atomic force microscope, a micro-nano mechanical analysis instrument, is used with a spherical probe with a diameter of 15-25 microns, preferably a silica spherical probe with a diameter of 20 microns, to increase the contact area and reduce local stress concentration and nano-scale mechanical inhomogeneity in micro-mechanical testing.

[0037] The micrometer-sized spherical probe is driven by the atomic force microscope instrument to approach and press into the biological scaffold at a speed of 20 μm / s. After reaching the preset sample deformation, the deformation position is precisely controlled, and the sample is compressed to 1 μm during the control, with a deformation position control accuracy of ±0.2%. At the same time, the deflection change of the atomic force microscope probe cantilever with time is analyzed to calculate the force relaxation process of the biological scaffold, and the results are referred to Figure 2 and Figure 3 wherein Figure 2 is a schematic diagram of the biological scaffold viscoelasticity stress relaxation test process of the atomic force microscope, i.e., a force-displacement curve, including the relationship between the displacement and stress of the probe in the stages of probe contacting the sample, pressing into the sample, sample stress relaxation, probe withdrawing, and probe leaving the sample. Figure 3 is a schematic diagram of the process of rapidly compressing the sample to deform and cause creep response after the probe contacts the sample, Figure 3 wherein A is the stress relaxation process of the sample with time, Figure 3Mid B is the sample strain constant in the strain displacement during the force relaxation process. After obtaining the corresponding biological scaffold force relaxation experimental data, the following analysis is carried out.

[0038] First, the judgment and selection of the contact point of the force relaxation curve of the atomic force microscope probe and the sample. The traditional method is to visually check and judge the force curve to continuously and significantly deviate from the zero force baseline, the probe moves away from the sample, and the force value is close to constant. However, this method is affected by subjectivity, noise, long-range attractive force (which causes the force curve to bend downward first), etc. In this embodiment, by taking the derivative of the force F-displacement Z curve, when dF / dZ is approximately equal to 0, the force is constant, and when the probe contacts the sample, the stiffness of the probe cantilever beam and the sample is coupled, causing dF / dZ to increase sharply, therefore, the point where the dF / dZ curve starts to significantly and stably increase from zero is usually defined as the contact point. Further, in order to avoid long-range attractive forces such as van der Waals forces, electrostatic forces, etc., in this embodiment, a small force threshold value is set according to the force set in the experiment, considering noise level and other factors, when the force value first continuously exceeds or continuously falls below the force threshold value, the displacement position of the threshold value is judged as the contact point, finally, the preliminary judgment of the visual method is realized, the force-displacement curve is derived in combination with the force threshold value judgment, and the precise judgment of the contact point is realized.

[0039] Then, the starting point of the force relaxation process is judged. Since the probe will have an impact effect and force surge and displacement mutation at the moment of contacting the sample, therefore, judging the starting point of the force relaxation is crucial for subsequent calculation of the viscoelastic properties of the sample. In this embodiment, the Matlab program automatically identifies the force surge or force mutation node, selects the 200-300th sampling point after this node as the starting point of force stability, and the 200th sampling point is preferred in this embodiment. Further, by intercepting the nodes of the contact point of the probe and the sample judged and the displacement reaching the preset position (1 μm) of the force relaxation, the distance between the contact point of the force relaxation curve and the starting point of the relaxation is determined, and at the same time, according to the experimental frequency, the corresponding experimental test points are intercepted and truncated, and the force relaxation process of the sample is determined.

[0040] In one specific embodiment of the present application, pre-processing and analysis of the force relaxation-time curve are also included. Microscopic mechanical analysis based on atomic force microscopy is easily affected by various factors such as environment, sample and human operation, causing the measured experimental data to be disturbed and fluctuated, resulting in inaccurate and non-reproducible viscoelastic analysis results of the final sample. In this specific embodiment, the Landweber-O'Sullivan-Schock smoothing method is used, by introducing physical constraints (such as positive definiteness and smoothness), when the SPAN value is closer to 0, it is determined that it is closer to the original data, and when it is closer to 1, it is determined that it is smoother. By repeatedly selecting a suitable starting point of force stability and using a smoothing processing algorithm until the data is stable.

[0041] In the calculation of the force relaxation characteristic time, in order to eliminate the differences in experimental conditions, make the method have better universality, extract the intrinsic material parameters, quantify the viscoelastic response of the sample, and at the same time, realize the cross-scale correlation. In this specific embodiment, the force relaxation-time curve obtained by the experiment is further normalized. By dividing the force F(t) at each time by the force F0 at the starting time of force relaxation, and then plotting it in the time domain, the normalized force relaxation curve is obtained. Referring to Figure 4 different samples, i.e. spinal cord biological scaffold, spinal cord gray matter and spinal cord white matter, under the same deformation conditions, different degrees of stress relaxation occur, Figure 4 A in the above formula is the original stress relaxation over time, Figure 4 B in the above formula is the normalized stress relaxation over time. In this specific embodiment, the time (t 1 / 2 ) used to relax the overall force to half (1 / 2*F0) is selected as the characteristic time for describing the viscoelastic characteristics of the biological scaffold and the spinal cord tissue.

[0042] Based on the obtained characteristic time, the evaluation of the micron-scale viscoelastic adaptability of the biological scaffold. The traditional method of evaluating whether the "elastic modulus ± standard deviation" of the biological scaffold overlaps with the tissue stiffness range cannot quantify the misfit risk, resulting in the failure of the biological scaffold implantation. Referring to Figure 5 the traditional biological scaffold evaluation method, the comparison of the microscopic viscoelastic properties (characteristic time) of the spinal cord biological scaffold, the spinal cord gray matter and the white matter, wherein the biological scaffold is tested at 61 random positions, the spinal cord gray matter is tested at 39 random positions, and the spinal cord white matter is tested at 45 random positions, Figure 5 A in the above formula is the average value of the characteristic time, Figure 5 B in the above formula is the distribution trend and range of the characteristic time.

[0043] In the specific embodiment, in order to quantitatively evaluate whether the micro viscoelastic properties of the biological stent match the target implanted tissue, the viscoelastic mechanical parameters (characteristic time) of the stent are taken as the diagnostic indicators, the micro viscoelastic properties (characteristic time) of the target implanted tissue site (gray matter and white matter of the spinal cord) are taken as the standard, the true positive rate and the false positive rate under different thresholds are calculated, and finally the quantitative and accurate evaluation of the micro viscoelastic adaptability of the biological stent is realized, as shown in FIG. 8. Figure 6 As shown in FIG. 8, the mechanical adaptability curve of the tested target, i.e., the biological stent, the gray matter of the spinal cord and the white matter of the spinal cord, is shown. It can be found from the curve that the viscoelastic properties of the gray matter and the white matter of the spinal cord are significantly different, the viscoelastic properties of the biological stent and the white matter of the spinal cord have no obvious difference, but the viscoelastic properties of the biological stent and the gray matter of the spinal cord are significantly different, thus proving that the viscoelastic mechanical adaptability of the biological stent and the white matter of the spinal cord is good, and the matching with the gray matter of the spinal cord is poor. Further, the threshold for determining whether the biological stent is consistent with the spinal cord tissue is given in the specific embodiment, as shown in the following table.

[0044] In view of the defects of the biological stent macro viscoelastic mechanical property analysis and evaluation method, an analysis method for analyzing the biological stent and the mechanical adaptability thereof is developed, the micro size ball probe is used to accurately test the viscoelastic properties of the micro structure of the biological stent, the applied load (nanonewton scale) is accurately controlled, the compression deformation of the stent is controlled, and the stress decay process with the test time is accurately tested, so as to accurately test the force relaxation process of the biological stent. In addition, an accurate biological stent micro scale viscoelastic mechanical adaptability analysis and evaluation method is provided, by comparing with the micro viscoelastic properties of the target site, the accurate evaluation of the micro mechanical adaptability of the biological stent is realized, the mechanical structure design and manufacturing of the biological stent are guided, and the implantation success rate and the treatment effect are improved.

[0045] In the specific embodiment of the present application, a biological stent viscoelastic evaluation system is also provided, comprising: A data acquisition module is configured to determine a target implantation site, test a biological stent using an atomic force microscope, and obtain force relaxation experimental data of the biological stent. A contact point calculation module is configured to determine a contact point of a force relaxation curve of the atomic force microscope probe and the biological stent based on the force relaxation experimental data. A starting point calculation module is configured to determine a time when a force signal of the biological stent is stable after the biological stent is compressed to a preset deformation as a starting point of force relaxation based on the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent. A characteristic time calculation module is configured to calculate a characteristic time corresponding to a time when a force value decays to half of the starting point force value as a micro viscoelastic property index of the biological stent with the starting point of force relaxation as a timing starting point. The evaluation module is configured to compare the characteristic time of the biological stent with an index of micro-viscoelastic properties of the target tissue implantation site to obtain a viscoelastic evaluation result of the biological stent.

[0046] In the embodiment, the data acquisition module is implemented by an atomic force microscope to accurately measure the micro-nano scale mechanical behavior of the biological stent, thereby providing a raw data basis for subsequent analysis. The contact point calculation module performs differential analysis and threshold judgment on the force relaxation experimental data, accurately identifies the initial contact position of the probe and the sample, and establishes a reference zero point for mechanical measurement.

[0047] The starting point calculation module identifies the force stable time point of the biological stent after reaching the preset deformation amount based on the determined contact point, eliminates impact interference, and ensures that the starting time point of the viscoelastic analysis is accurate and reliable. The characteristic time calculation module takes the force relaxation starting point as a reference, quantifies the force value decay process, converts the complex viscoelastic behavior into a single characteristic time parameter, and realizes the standardized characterization of material properties.

[0048] The evaluation module directly compares the characteristic time parameter of the biological stent with the corresponding parameter of the target tissue implantation site to establish a mechanical adaptability evaluation system at the micro scale. The modules form a complete technical closed loop: the output of the data acquisition module is the input of the contact point calculation module, the result of the contact point calculation module provides a reference for the starting point calculation module, the characteristic time calculation module relies on the output parameters of the previous modules, and the final evaluation module integrates all processing results to complete the adaptability judgment.

[0049] This modular design ensures the coherence of the data processing flow and the implementability of the technical scheme. Each module assumes a specific function and cooperates with each other to realize the complete analysis process from raw data acquisition to final evaluation output. The modular architecture of the system also facilitates the maintenance and extension of the technical scheme, and provides flexible technical support for viscoelastic evaluation in different application scenarios.

[0050] Also provided in the embodiments of the present application is a computer device, which specifically comprises a processor and a memory. The memory is used to store a computer program, and the computer program comprises program instructions. The processor is used to execute the program instructions stored in the computer storage medium. The processor can be a central processing unit (CPU), and can also be other general-purpose processors, digital signal processors (DSP), application specific integrated circuits (ASIC), field programmable gate arrays (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The processor is the computing core and control core of the terminal, and is suitable for implementing one or more instructions, and is specifically suitable for loading and executing one or more instructions to implement a corresponding method flow or a corresponding function. The processor in the embodiments of the present application can be used to determine a target implantation site, test a biological stent by using an atomic force microscope, obtain force relaxation experimental data of the biological stent, judge a contact point of a force relaxation curve of the atomic force microscope probe and the biological stent according to the force relaxation experimental data, determine a time point at which a force signal of the biological stent is stable after the biological stent is compressed to a preset deformation amount as a starting point of force relaxation according to the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent, calculate a characteristic time corresponding to a time when a force value decays to half of a force value of the starting point as a micro-viscoelasticity characteristic index of the biological stent with the starting point of force relaxation as a timing starting point, and compare the characteristic time of the biological stent with the micro-viscoelasticity characteristic index of the target implantation tissue site to obtain a viscoelasticity evaluation result of the biological stent.

[0051] The embodiment of the present application also provides a storage medium, specifically, a computer readable storage medium, which is a memory device in a terminal device and is used for storing programs and data. It can be understood that the computer readable storage medium herein can include a built-in storage medium in the terminal device, and of course can also include an extended storage medium supported by the terminal device. The computer readable storage medium provides a storage space, which stores an operating system of the terminal. In addition, one or more instructions suitable for being loaded and executed by the processor are also stored in the storage space, and the instructions can be one or more computer programs (including program codes). It should be noted that the computer readable storage medium herein can be a high-speed RAM memory or a non-volatile memory such as at least one disk memory. The one or more instructions stored in the computer readable storage medium can be loaded and executed by the processor to implement the corresponding steps of the method in the above embodiment; the one or more instructions in the computer readable storage medium are loaded and executed by the processor to determine a target implantation site, test the biological stent by using an atomic force microscope, and obtain force relaxation experiment data of the biological stent; determine a contact point of a force relaxation curve of the atomic force microscope probe and the biological stent according to the force relaxation experiment data; determine a time point at which the force signal of the biological stent is stable after the biological stent is compressed to a preset deformation amount as a starting point of force relaxation according to the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent; take the starting point of force relaxation as a timing starting point, calculate a characteristic time corresponding to a time when the force value decays to half of the starting point force value as a micro-viscoelasticity characteristic index of the biological stent; and compare the characteristic time of the biological stent with the micro-viscoelasticity characteristic index of the target implantation tissue site to obtain a viscoelasticity evaluation result of the biological stent.

[0052] Those skilled in the art should understand that the embodiments of the present application can be provided as a method, a system, or a computer program product. Therefore, the present application can adopt a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Moreover, the present application can adopt a computer program product in the form of being implemented on one or more computer usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) containing computer usable program codes.

[0053] The computer program instructions can also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer-implemented process such that the instructions which execute on the computer or other programmable apparatus provide steps for implementing the functions specified in the flowchart block or blocks. Figure 1 one or more flow or blocks Figure 1 means for functionally implementing the steps listed in the flowchart block or blocks.

[0054] These computer program instructions can also be stored in a computer-readable memory that can direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture including instructions which implement the function specified in the flowchart block or blocks. Figure 1 one or more flow or blocks Figure 1 means for functionally implementing the steps listed in the flowchart block or blocks.

[0055] The computer program instructions can also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer-implemented process such that the instructions which execute on the computer or other programmable apparatus provide steps for implementing the functions specified in the flowchart block or blocks. Figure 1 one or more flow or blocks Figure 1 means for functionally implementing the steps listed in the flowchart block or blocks.

[0056] The principles and advantages of the present application have been described in above particularity, it is to be understood that the application is not limited to the exemplary embodiments described, and that numerous modifications can be made to the illustrative embodiments without departing from the spirit or essential characteristics of the application. The scope of the application is therefore intended to be defined only by the scope of the claims appended hereto, and not by the explicit description hereinabove. No limitation is intended to the details of construction or design herein shown, other than as described in the claims directly or indirectly attached hereto, which limitation is intended to be subservient to the generic scope of the application.

[0057] Furthermore, it should be understood that although the specification is described in terms of embodiments, each of which contains only one independent technical solution, the specification is described in this way only for the sake of clarity, and the skilled person should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that the skilled person can understand. The above is only to illustrate the technical idea of the present application, and cannot limit the protection scope of the present application. Any modification made on the basis of the technical solutions according to the technical idea of the present application falls within the protection scope of the claims of the present application.

Claims

1. A method of bio-scaffold viscoelasticity assessment, characterized by, The method comprises the following steps: determining a target implantation site, testing a biological stent using an atomic force microscope, and obtaining force relaxation experimental data of the biological stent; judging a contact point of a force relaxation curve of the atomic force microscope probe and the biological stent according to the force relaxation experimental data; determining a time point at which a force signal is stable after the biological stent is compressed to a preset deformation as a starting point of force relaxation according to the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent; calculating a characteristic time corresponding to a time point at which a force value decays to half of a force value at the starting point of force relaxation as a micro-viscoelasticity characteristic index of the biological stent, with the starting point of force relaxation as a time starting point; comparing the characteristic time of the biological stent with the micro-viscoelasticity characteristic index of the target implantation tissue site to obtain a viscoelasticity evaluation result of the biological stent.

2. The method of claim 1, wherein the bio-scaffold is a tissue engineered blood vessel. The method of determining the target implantation site, testing the biological stent using the atomic force microscope, and obtaining the force relaxation experimental data of the biological stent comprises the following steps: the atomic force microscope uses a spherical probe with a diameter of 15-25 microns to approach the biological stent at an approaching speed of 15-25 μm / s; after the probe contacts the biological stent, the biological stent is continuously compressed to a preset deformation; the preset deformation is kept constant, the deflection change of the cantilever beam of the atomic force microscope probe with time is analyzed, the force relaxation process of the biological stent is calculated, and the force relaxation experimental data of the biological stent are obtained.

3. The method of claim 1, wherein the bio-scaffold is a tissue engineered blood vessel. The method of judging the contact point of the force relaxation curve of the atomic force microscope probe and the biological stent according to the force relaxation experimental data comprises the following steps: the force F-displacement Z curve in the force relaxation experimental data is differentiated to calculate and identify an inflection point at which the value of dF / dZ starts to stably increase from zero; a force threshold is set based on the noise level of an experimental environment, and a displacement position at which the force value in the force F-displacement Z curve first continuously exceeds the force threshold is identified; the contact point is comprehensively determined in combination with the inflection point and the displacement position.

4. The method of claim 1, wherein the bio-scaffold is a hydrogel. The method of determining a time point at which a force signal is stable after the biological stent is compressed to a preset deformation as a starting point of force relaxation comprises the following steps: a force surge node generated when the atomic force microscope probe reaches the preset deformation is identified; a time point corresponding to 200-300 sampling points selected from the force surge node backward is selected as the time point at which the force signal is stable.

5. The method of claim 1, wherein the bio-scaffold is a hydrogel. The method of calculating a characteristic time corresponding to a time point at which a force value decays to half of a force value at the starting point of force relaxation comprises the following steps: ​ the force relaxation experimental data comprise a force relaxation-time curve, the force relaxation-time curve is normalized, and the ratio of a force F(t) at each time point to a force F0 at the starting point of force relaxation is calculated; a time point at which the ratio first reaches 0.5 is identified, and a time difference between the time point and the starting point of force relaxation is calculated as the characteristic time.

6. The method of viscoelastic evaluation of a biological stent according to claim 5, wherein Before the force relaxation-time curve is normalized, the force relaxation-time curve is also preprocessed, which comprises the following steps: the starting point of force relaxation is repeatedly selected, and a smoothing processing algorithm is used for the force relaxation-time curve until the force relaxation-time curve is stable.

7. The method of claim 1, wherein the bio-scaffold is a tissue engineered blood vessel. The method of comparing the characteristic time of the biological stent with the micro-viscoelasticity characteristic index of the target implantation tissue site comprises the following steps: a plurality of characteristic time measurement values of the biological stent and the target implantation tissue site are respectively obtained to form a characteristic time distribution; Based on the characteristic time distribution, true positive rate and false positive rate under different judgment thresholds are calculated; The working characteristic curve of the biological stent and the target value such as tissue is drawn to obtain the viscoelasticity evaluation result of the biological stent.

8. A biological scaffold viscoelasticity evaluation system characterized by, The method comprises the steps of: The data acquisition module is configured to determine a target implantation site, test the biological stent using an atomic force microscope, and obtain force relaxation experimental data of the biological stent; The contact point calculation module is configured to determine the contact point between the atomic force microscope probe and the force relaxation curve of the biological stent according to the force relaxation experimental data; The start point calculation module is configured to determine the time when the force signal is stable after the biological stent is compressed to a preset deformation amount as the start point of force relaxation according to the contact point between the atomic force microscope probe and the force relaxation curve of the biological stent; The characteristic time calculation module is configured to take the start point of force relaxation as the starting point of timing, calculate the characteristic time corresponding to the time when the force value decays to half of the start point force value, and take the characteristic time as the micro viscoelasticity characteristic index of the biological stent; The evaluation module is configured to compare the characteristic time of the biological stent with the micro viscoelasticity characteristic index of the target implantation tissue site, and obtain the viscoelasticity evaluation result of the biological stent.

9. A computer device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, The processor executes the computer program to realize the steps of the biological stent viscoelasticity evaluation method according to any one of claims 1 to 7.

10. A computer-readable storage medium storing a computer program, the computer program comprising instructions that, when executed by a computer, cause the computer to perform the method of any one of claims 1 to 9. The computer program is executed by the processor to realize the steps of the biological stent viscoelasticity evaluation method according to any one of claims 1 to 7.

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