Construction method of dynamic three-dimensional circulating ventilation stretching model for ventilator-induced lung injury

Abstract

The invention relates to the field of model construction and control, and provides a method for constructing a dynamic three-dimensional circulating ventilation tensile model for lung injury induced by a respirator, which simulates pathological and mechanical characteristics of pulmonary alveoli in a three-dimensional spherical stress environment by constructing a dynamic structure model, so that the simulation is more in line with an actual pathological scene, and the simulation accuracy is improved. The dynamic structure model is subjected to circulating ventilation stretching adjustment through a pneumatic control algorithm, so that the simulation state is more accurate, long-time circulating ventilation stretching can be adapted, continuous simulation stimulation is maintained, and multi-cell co-culture and sequential interaction simulation are realized through simulation optimization; according to the method, the construction accuracy and simulation authenticity of the dynamic three-dimensional circulating ventilation stretching model for the ventilator-induced lung injury are improved.

Description

Methods for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury Technical Field

[0001] This invention relates to the field of model construction and control, and in particular to a method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury. Background Technology

[0002] Mechanical ventilation (MV), a key supportive treatment for critically ill patients, improves patient outcomes by providing respiratory support and allowing respiratory muscle rest. However, MV itself can lead to ventilator-induced lung injury (VILI), characterized by inflammatory cell infiltration, hyaline membrane formation, and pulmonary edema. The core pathological mechanism lies in the disruption of the pulmonary microvascular endothelial-epithelial barrier and the resulting uncontrolled inflammatory cascade. VILI not only exacerbates the primary disease process but also significantly prolongs the treatment period and increases mortality, becoming a major clinical challenge that urgently needs to be addressed. However, the multi-factor coupling of the complex in vivo microenvironment (such as heterogeneous three-dimensional stress, hemodynamics, and inflammatory factor cascades) hinders the analysis of the independent effects of single variables (such as specific mechanical stimuli or cellular temporal responses). Existing in vitro models have significant technical limitations, severely restricting their value in mechanism research and clinical translation potential: 1. Mechanical distortion: Mainstream devices (such as Flexcell and CELL TANK) can only generate two-dimensional planar strain, which cannot simulate the pathomechanical characteristics of alveoli under three-dimensional spherical stress environment; 2. Insufficient long-term stimulation maintenance capacity: The short-term power sources (such as injection pumps) on which microfluidic biomimetic models rely are difficult to achieve the continuous cell stretch stimulation (≥6 hours) required for VILI studies; 3. Throughput limitation: The limited number of culture chambers cannot meet the needs of large-scale cell cluster studies, restricting high-throughput drug screening; 4. Lack of physiological function: Traditional cell immersion culture mode isolates gas exchange and lacks simulation of the key gas-liquid interface physiological function of alveolar epithelium.

[0003] 5. Economic and Practical Limitations: Traditional in vitro models (especially microfluidic chips with complex fluid channels) often use plastic components or disposable bonded designs, which cannot withstand high-temperature and high-pressure sterilization (e.g., 121°C, 15psi, 20min), resulting in them being mostly single-use devices. This not only significantly increases experimental costs but also limits the long-term, stable application of the models due to the inability to guarantee good sterility and batch-to-batch consistency.

[0004] In summary, the shortcomings of existing technologies in areas such as the fidelity of three-dimensional mechanical simulation, the ability to maintain long-term dynamic stimulation, high-throughput compatibility, simulation of the physiological functions of the gas-liquid interface, and cost-effectiveness and practicality significantly weaken the pathological relevance of VILI in vitro models, thereby reducing the clinical translation efficacy of potential therapeutic targets and diagnostic biomarkers. Therefore, developing a biomimetic alveolar platform that can simultaneously achieve three-dimensional dynamic mechanical simulation, large-scale cell culture, a realistic gas-liquid interface environment, and low-cost reusability is a key technological pathway for accurately analyzing the spatiotemporal dynamic interaction network of lung epithelial / endothelial / macrophages in the VILI process and accelerating the translation of medical research. Summary of the Invention

[0005] Based on this, the present invention proposes a method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury. By constructing a dynamic structural model to simulate the pathomechanical characteristics of alveoli under three-dimensional spherical stress environment, the simulation is made more consistent with the actual pathological scenario. Then, the dynamic structural model is adjusted for circulatory ventilation stretching through a pneumatic control algorithm, making the simulation state more accurate and adaptable to long-term circulatory ventilation stretching, maintaining continuous simulation stimulation. Furthermore, through simulation optimization, multi-cell co-culture and temporal interaction simulation are realized. The present invention improves the accuracy and simulation realism of constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury.

[0006] This invention proposes a method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury, comprising: constructing a dynamic structural model, the dynamic structural model being based on a three-layer structure, the three-layer structure including a bottom layer, a middle layer, and a top layer; performing circulatory ventilation stretching adjustment on the dynamic structural model according to a pneumatic control algorithm, the pneumatic control algorithm being based on a PID control algorithm and an adaptive respiratory rhythm control algorithm, the PID control algorithm being based on dynamic deformation rate, and the adaptive respiratory rhythm control algorithm being based on ventilation frequency; and performing simulation optimization based on the dynamic structural model to obtain a final dynamic three-dimensional circulatory ventilation stretching model.

[0007] In summary, based on the above-mentioned method for constructing a dynamic three-dimensional circulatory stretching model of ventilator-induced lung injury, a dynamic structural model is constructed to simulate the pathomechanical characteristics of alveoli under three-dimensional spherical stress environment, making the simulation more consistent with the actual pathological scenario. Then, the dynamic structural model is adjusted for circulatory stretching through pneumatic control algorithms, making the simulation state more accurate and adaptable to long-term circulatory stretching, maintaining continuous simulation stimulation. Furthermore, through simulation optimization, multi-cell co-culture and temporal interaction simulation are realized. This invention improves the accuracy and simulation realism of constructing a dynamic three-dimensional circulatory stretching model of ventilator-induced lung injury. Specifically, a dynamic structural model is constructed based on a three-layer structure, comprising a bottom layer, a middle layer, and a top layer, making the simulation more consistent with actual pathological scenarios. The dynamic structural model is then subjected to cyclic ventilation stretching adjustment using a pneumatic control algorithm based on a PID control algorithm and an adaptive respiratory rhythm adjustment algorithm. The PID control algorithm is based on dynamic deformation rate, and the adaptive respiratory rhythm adjustment algorithm is based on ventilation frequency, resulting in a more accurate simulation state and the ability to adapt to long-term cyclic ventilation stretching, maintaining continuous simulation stimulation. Simulation optimization is performed based on the dynamic structural model to obtain a final dynamic three-dimensional cyclic ventilation stretching model, achieving multi-cell co-culture and temporal interaction simulation. This invention improves the accuracy and simulation realism of constructing a dynamic three-dimensional cyclic ventilation stretching model for ventilator-induced lung injury.

[0008] Furthermore, the step of constructing the dynamic structural model specifically includes: constructing a three-layer structure of the dynamic structural model, the three-layer structure including a bottom layer, an intermediate layer, and a top layer; the bottom layer is a PDMS base layer, the PDMS base layer including a gas microchannel structure and a channel chamber structure; the intermediate layer is a cell culture substrate and a deformation generation layer, the intermediate layer undergoes non-planar strain; the top layer is a PDMS capping layer, the PDMS capping layer including a gas path interface and a cell culture chamber, the top layer is a closed gas phase environment, the top layer and the bottom layer are physically isolated, the physical isolation is based on the effect of the intermediate layer; assembling the three-layer structure to obtain the dynamic structural model.

[0009] Furthermore, the step of assembling the three-layer structure to obtain a dynamic structural model specifically includes: performing plasma treatment on the bottom-middle layer contact surface and the top-middle layer contact surface of the three-layer structure, followed by overnight curing treatment to bond the bottom-middle layer contact surface and the top-middle layer contact surface, wherein the temperature of the overnight curing treatment is kept constant at 65 degrees Celsius; performing alignment and sealing treatment on the three-layer structure to ensure that the three-layer structure is in a gas-liquid isolation state, wherein a stable gas-liquid interface exists in the gas-liquid isolation state; and connecting the bottom and top layers with gas paths to obtain a dynamic structural model.

[0010] Furthermore, the step of performing cyclic ventilation and stretching adjustment on the dynamic structural model according to the aerodynamic control algorithm specifically includes: cyclic ventilation of the dynamic structural model and real-time calculation of the dynamic deformation rate of the intermediate layer. The specific algorithm for the dynamic deformation rate is as follows: ,in, Indicates the dynamic deformation rate. Indicates time, This represents the area of ​​the intermediate layer at the current moment. This represents the original intermediate layer area; the simulated deformation error is calculated based on a preset deformation rate threshold and the dynamic deformation rate. The specific algorithm for calculating the simulated deformation error is as follows: ,in, Indicates the simulated deformation error. This represents a preset deformation rate threshold; PID control is performed based on the simulated deformation error to obtain the regulated air pressure value. The specific algorithm for PID control is as follows: ,in, This indicates the adjustment of the air pressure value. , , The PID coefficient is represented; closed-loop negative feedback regulation is performed based on the adjusted air pressure value; and ventilation modes for different pathological states are simulated based on the adaptive respiratory rhythm algorithm.

[0011] Furthermore, the step of simulating ventilation modes for different pathological states based on the adaptive respiratory rhythm algorithm specifically includes: obtaining the respiratory time for different pathological states to adaptively calculate the ventilation frequency for the ventilation mode simulation. The specific algorithm for the ventilation frequency is as follows: ,in, Indicates ventilation frequency. and These represent the inspiratory and expiratory times, respectively; the timing is adjusted according to the ventilation frequency to perform pneumatic control for long-duration ventilation simulation.

[0012] Furthermore, the step of simulating and optimizing the dynamic structural model to obtain the final dynamic three-dimensional circulatory ventilation stretching model specifically includes: seeding lung epithelial cells and endothelial cells on the surface of the intermediate layer of the dynamic structural model and setting the dynamic structural model in a periodic aerodynamic state; then transferring macrophages to the bottom layer of the dynamic structural model for co-culture of alveolar-vascular-immune cells; performing inflammatory factor analysis and simulating and optimizing the current dynamic structural model to obtain the final dynamic three-dimensional circulatory ventilation stretching model.

[0013] This invention proposes a system for constructing a dynamic three-dimensional circulatory stretching model of ventilator-induced lung injury, comprising: a construction module for constructing a dynamic structural model, the dynamic structural model being based on a three-layer structure, the three-layer structure including a bottom layer, a middle layer, and a top layer; an adjustment module for adjusting the dynamic structural model for circulatory stretching according to a pneumatic control algorithm, the pneumatic control algorithm being based on a PID control algorithm and an adaptive respiratory rhythm control algorithm, the PID control algorithm being based on dynamic deformation rate, and the adaptive respiratory rhythm control algorithm being based on ventilation frequency; and a simulation optimization module for performing simulation optimization based on the dynamic structural model to obtain a final dynamic three-dimensional circulatory stretching model.

[0014] Furthermore, the construction module also includes: a three-layer structure for constructing a dynamic structural model, comprising a bottom layer, a middle layer, and a top layer; the bottom layer is constructed based on PDMS casting, and has gas microchannels and four channel chambers, the gas microchannels being 1mm wide, 15mm long, and 0.3mm deep, and the channel chambers being circular holes with a diameter of 35mm and a depth of 0.3mm, with cell transfer slots provided at the edges of the bottom layer; the middle layer is constructed based on PDMS casting and solidification, and is a PDMS elastic membrane with a thickness of 300μm, the PDMS elastic membrane undergoing non-planar strain under gas pressure, the deformation rate of the non-planar strain ranging from 5% to 50%; the top layer is constructed based on PDMS casting, and has culture wells and four channel chambers, the channel chambers being circular holes with a diameter of 35mm and a depth of 0.3mm.

[0015] The present invention also provides a storage medium storing one or more programs, which, when executed by a processor, implement the method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury as described above.

[0016] The present invention also provides a computer device, the computer device including a memory and a processor, wherein: the memory is used to store a computer program; the processor is used to execute the computer program stored in the memory to implement the method for constructing the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury as described above. Attached Figure Description

[0017] Figure 1 is a flowchart of the construction method of the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury proposed in the first embodiment of the present invention; Figure 2 is a structural schematic diagram of the construction system of the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury proposed in the second embodiment of the present invention; Figure 3 is a flowchart of the construction of the dynamic structural model of the present invention; Figure 4 is an example of interleukin-1 in the verification experiment of the first embodiment of the present invention. Data graphs; Figure 5 shows the data of interleukin-6 in the verification experiment of the first embodiment of the present invention; Figure 6 shows the data of tumor necrosis factor in the verification experiment of the first embodiment of the present invention. Figure 7 shows the LDH level data in the cell supernatant during the verification experiment of the first embodiment of the present invention; Figure 8 shows the cell survival distribution data during the verification experiment of the first embodiment of the present invention; Figure 9 shows the cell survival rate data during the verification experiment of the first embodiment of the present invention; The following detailed embodiments will further illustrate the present invention in conjunction with the above figures. Detailed Implementation

[0018] To facilitate understanding of the present invention, a more complete description will be given below with reference to the accompanying drawings. Several embodiments of the invention are illustrated in the drawings. However, the invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

[0019] It should be noted that when a component is said to be "fixed to" another component, it can be directly on the other component or there may be an intervening component. When a component is said to be "connected to" another component, it can be directly connected to the other component or there may be an intervening component. The terms "vertical," "horizontal," "left," "right," and similar expressions used in this document are for illustrative purposes only.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0021] Please refer to Figure 1, which shows a flowchart of the construction method of the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury proposed in the first embodiment of the present invention. The construction method of this dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury includes steps S01 to S03, wherein: Step S01: Constructing a dynamic structural model; It should be noted that in this embodiment, the dynamic structural model is based on a three-layer structure, which includes a bottom layer, an intermediate layer and a top layer. The three-layer structure of the dynamic structural model includes a bottom layer, an intermediate layer and a top layer. The specific construction process of the dynamic structural model is shown in Figure 3; The bottom layer is a PDMS base layer, which includes a gas microchannel structure and a channel chamber structure; The intermediate layer is a cell culture base and a deformation generation layer, which undergoes non-planar strain; The top layer is a PDMS capping layer, which includes a gas path interface and a cell culture chamber. The top layer is a closed gas phase environment, and the top layer and the bottom layer are physically isolated, which is based on the action of the intermediate layer; The three-layer structure is assembled to obtain the dynamic structural model.

[0022] The bottom-middle layer contact surface and the top-middle layer contact surface in the three-layer structure are subjected to plasma treatment and then overnight curing treatment to bond the bottom-middle layer contact surface and the top-middle layer contact surface, respectively. The temperature of the overnight curing treatment is kept constant at 65 degrees Celsius. The three-layer structure is aligned and sealed to make the three-layer structure in a gas-liquid isolation state with a stable gas-liquid interface. The bottom layer and the top layer are connected by gas path to obtain a dynamic structural model.

[0023] Step S02: The dynamic structural model is subjected to cyclic ventilation and stretching adjustment according to the pneumatic control algorithm. It should be noted that in this embodiment, the pneumatic control algorithm is based on a PID control algorithm and an adaptive respiratory rhythm control algorithm. The PID control algorithm is based on the dynamic deformation rate, and the adaptive respiratory rhythm control algorithm is based on the ventilation frequency. The dynamic structural model is cyclically ventilated, and the dynamic deformation rate of the intermediate layer is calculated in real time. The specific algorithm for the dynamic deformation rate is as follows: ,in, Indicates the dynamic deformation rate. Indicates time, This represents the area of ​​the intermediate layer at the current moment. This represents the original intermediate layer area; the simulated deformation error is calculated based on a preset deformation rate threshold and the dynamic deformation rate. The specific algorithm for calculating the simulated deformation error is as follows: ,in, Indicates the simulated deformation error. This represents a preset deformation rate threshold; PID control is performed based on the simulated deformation error to obtain the regulated air pressure value. The specific algorithm for PID control is as follows: ,in, This indicates the adjustment of the air pressure value. , , The PID coefficient is represented; closed-loop negative feedback regulation is performed based on the adjusted air pressure value; and ventilation modes for different pathological states are simulated based on the adaptive respiratory rhythm algorithm.

[0024] The respiratory time under different pathological states is obtained to adaptively calculate the ventilation frequency of the simulated ventilation mode. The specific algorithm for the ventilation frequency is as follows: ,in, Indicates ventilation frequency, and These represent the inspiratory and expiratory times, respectively; the timing is adjusted according to the ventilation frequency to perform pneumatic control for long-duration ventilation simulation.

[0025] Step S03: Perform simulation optimization based on the dynamic structural model to obtain the final dynamic three-dimensional circulating ventilation stretching model; it should be noted that in this embodiment, lung epithelial cells and endothelial cells are seeded on the surface of the middle layer of the dynamic structural model, and the dynamic structural model is set in a periodic aerodynamic state; then macrophages are transferred to the bottom layer of the dynamic structural model for co-culture of alveolar-vascular-immune cells; inflammatory factor analysis is performed, and the current dynamic structural model is simulated and optimized to obtain the final dynamic three-dimensional circulating ventilation stretching model.

[0026] It should be noted that, in verifying the model of this invention and comparing it with existing models, in the verification experiment of this embodiment, the model used a 30% deformation area to stretch the alveolar epithelial cell line of MLE-12 mice. After collecting samples at different time points, RT-qPCR technology, cell supernatant LDH detection kit, and flow cytometry were used to detect cell apoptosis to verify the changes of various indicators at different time points. The conclusion is that, as the stretching time increases, cell damage worsens and the composition of cell supernatant changes accordingly. This ventilator-induced lung injury dynamic three-dimensional circulatory stretching model can basically simulate the pathomechanical characteristics of alveoli under three-dimensional spherical stress environment in vitro, making it more consistent with the actual pathological scenario. According to statistical analysis: all data are expressed as mean ± standard deviation (Mean ± SD). Statistical analysis was performed using GraphPad Prism software. The Student's t test was used for comparison between two groups, and one-way ANOVA was used for comparison between multiple groups. P < 0.05 was considered statistically significant. After collecting samples at different time points, RT-qPCR was used to verify changes in cellular inflammatory factor levels (see Figures 4, 5, and 6). The conclusion is that cellular inflammatory expression levels increased with prolonged stretching time, with interleukin-1β highest at 24 hours, interleukin-6 highest at 6 hours, and tumor necrosis factor-α highest at 9 hours. After collecting samples at different time points, LDH levels in the cell supernatant were detected using an LDH detection kit (see Figure 7). The conclusion is that LDH levels in the cell supernatant increased with prolonged stretching time, reaching their highest levels at 6 hours and 24 hours. After collecting samples at different time points, flow cytometry was used to detect changes in cell apoptosis (see Figures 8 and 9). The conclusion is that cell viability decreased with prolonged stretching time, with the lowest cell viability in the 12-hour group and the highest rate of mechanical cell damage in the 24-hour group.

[0027] The specific comparison between the model of this invention and the existing technology model is shown in Table 1 below: Table 1 As shown in Table 1, existing in vitro research models for ventilator-induced lung injury (VILI) mainly include two-dimensional periodic mechanical stretching cell models (Flexcell), air-liquid interface periodic pressure models (CPAD), and microfluidic lung organ-on-a-chip models. Among these, the two-dimensional periodic mechanical stretching cell model (Flexcell) is typically based on an elastic membrane substrate, applying uniaxial or biaxial periodic stretching to alveolar epithelial cells or endothelial cells to simulate mechanical stimulation under different tidal volume ventilation conditions. This type of model has a simple structure and easily controllable parameters, but its stress form is mainly planar stretching, making it difficult to realistically reflect the isotropic or non-uniform stress distribution experienced by alveoli in a three-dimensional spherical structure. Furthermore, it is mostly limited to single-cell type culture and cannot simulate the pathological process of multi-cell synergistic action in the alveolar microenvironment. The air-liquid interface periodic pressure model (CPAD) simulates the effect of airway pressure changes on alveolar epithelium during mechanical ventilation by applying periodic pressure fluctuations at the cell-air exposure interface. While these models incorporate ventilation pressure to some extent, their mechanical stimulation primarily relies on pressure changes, lacking simulation of alveolar volume changes and three-dimensional structural deformation. Furthermore, the stimulation patterns are often short-term or discontinuous, making it difficult to achieve stable long-term cyclic ventilation. Recent developments in lung organ-on-a-chip (VILI) or ventilation-on-a-chip models utilize microfluidic technology to construct epithelial-endothelial co-culture structures and introduce periodic stretching or fluid shear forces, improving structural complexity and physiological relevance. However, these models often rely on fixed microstructures or planar membrane deformation, limiting the amplitude and spatial distribution of stretching deformation. This makes it difficult to accurately reconstruct the dynamic three-dimensional expansion-contraction process of alveoli under high-volume ventilation conditions. Moreover, their ventilation regulation often uses preset parameter control, lacking closed-loop control capabilities based on real-time mechanical states. Therefore, existing VILI in vitro models generally suffer from insufficient three-dimensional structural simulation, significant deviations between the mechanical stress field and real alveoli, limited precision in ventilation stretching regulation, and insufficient simulation capabilities for multi-cell temporal interactions. Consequently, they struggle to stably and accurately reproduce the key pathomechanical characteristics of ventilator-induced lung injury under long-term cyclic ventilation conditions.

[0028] In summary, based on the above-mentioned method for constructing a dynamic three-dimensional circulatory stretching model of ventilator-induced lung injury, a dynamic structural model is constructed to simulate the pathomechanical characteristics of alveoli under three-dimensional spherical stress environment, making the simulation more consistent with the actual pathological scenario. Then, the dynamic structural model is adjusted for circulatory stretching through pneumatic control algorithms, making the simulation state more accurate and adaptable to long-term circulatory stretching, maintaining continuous simulation stimulation. Furthermore, through simulation optimization, multi-cell co-culture and temporal interaction simulation are realized. This invention improves the accuracy and simulation realism of constructing a dynamic three-dimensional circulatory stretching model of ventilator-induced lung injury. Specifically, a dynamic structural model is constructed based on a three-layer structure, comprising a bottom layer, a middle layer, and a top layer, making the simulation more consistent with actual pathological scenarios. The dynamic structural model is then subjected to cyclic ventilation stretching adjustment using a pneumatic control algorithm based on a PID control algorithm and an adaptive respiratory rhythm adjustment algorithm. The PID control algorithm is based on dynamic deformation rate, and the adaptive respiratory rhythm adjustment algorithm is based on ventilation frequency, resulting in a more accurate simulation state and the ability to adapt to long-term cyclic ventilation stretching, maintaining continuous simulation stimulation. Simulation optimization is performed based on the dynamic structural model to obtain a final dynamic three-dimensional cyclic ventilation stretching model, achieving multi-cell co-culture and temporal interaction simulation. This invention improves the accuracy and simulation realism of constructing a dynamic three-dimensional cyclic ventilation stretching model for ventilator-induced lung injury.

[0029] Please refer to Figure 2, which shows a schematic diagram of the construction system for the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury proposed in the second embodiment of the present invention. The system includes: a construction module 10 for constructing a dynamic structural model, the dynamic structural model being based on a three-layer structure, the three-layer structure including a bottom layer, a middle layer, and a top layer; the construction module further includes: the three-layer structure for constructing the dynamic structural model, the three-layer structure including a bottom layer, a middle layer, and a top layer; the bottom layer is constructed using PDMS casting, the bottom layer having gas microchannels and four channel chambers, the gas microchannels having a width of 1 mm, a length of 15 mm, and a depth of 0.3 mm, the channel chambers being circular holes with a diameter of 35 mm and a depth of 0.3 mm, and cell transfer slots being provided at the edge of the bottom layer; the middle layer is cast and solidified using PDMS. The structure comprises: an intermediate layer consisting of a 300 μm thick PDMS elastic membrane, which undergoes non-planar strain under pneumatic pressure, with a deformation rate ranging from 5% to 50%; a top layer constructed by PDMS casting, comprising culture wells and four channel chambers, each a circular hole with a diameter of 35 mm and a depth of 0.3 mm; an adjustment module 20 for performing cyclic ventilation stretching adjustment on the dynamic structural model according to a pneumatic control algorithm based on a PID control algorithm and an adaptive respiratory rhythm control algorithm, wherein the PID control algorithm is based on the dynamic deformation rate and the adaptive respiratory rhythm control algorithm is based on the ventilation frequency; and a simulation optimization module 30 for performing simulation optimization on the dynamic structural model to obtain a final dynamic three-dimensional cyclic ventilation stretching model.

[0030] The present invention also proposes a computer storage medium storing one or more programs, which, when executed by a processor, implement the above-described method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury.

[0031] The present invention also proposes a computer device, including a memory and a processor, wherein the memory is used to store computer programs, and the processor is used to execute the computer programs stored in the memory to realize the above-mentioned method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury.

[0032] Those skilled in the art will understand that the logic and / or steps represented in the flowchart or otherwise described herein, for example, can be considered as a sequenced list of executable instructions for implementing logical functions, and can be embodied in any computer-readable medium for use by, or in conjunction with, an instruction execution system, apparatus, or device (such as a computer-based system, a processor-included system, or other system that can fetch and execute instructions from, an instruction execution system, apparatus, or device). For the purposes of this specification, "computer-readable medium" can mean any means that can contain stored, communicated, propagated, or transmitted programs for use by, or in conjunction with, an instruction execution system, apparatus, or device.

[0033] More specific examples of computer-readable media (a non-exhaustive list) include: electrical connections (electronic devices) having one or more wires, portable computer disk drives (magnetic devices), random access memory (RAM), read-only memory (ROM), erasable and editable read-only memory (EPROM or flash memory), fiber optic devices, and portable optical disc read-only memory (CDROM). Furthermore, computer-readable media can even be paper or other suitable media on which the program can be printed, because the program can be obtained electronically, for example, by optically scanning the paper or other medium, followed by editing, interpreting, or otherwise processing as necessary, and then stored in computer memory.

[0034] It should be understood that various parts of the present invention can be implemented in hardware, software, firmware, or a combination thereof. In the above embodiments, multiple steps or methods can be implemented in software or firmware stored in memory and executed by a suitable instruction execution system. For example, if implemented in hardware, as in another embodiment, it can be implemented using any one or a combination of the following techniques known in the art: discrete logic circuits having logic gates for implementing logical functions on data signals, application-specific integrated circuits (ASICs) having suitable combinational logic gates, programmable gate arrays (PGAs), field-programmable gate arrays (FPGAs), etc.

[0035] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0036] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of this patent should be determined by the appended claims.

Claims

1. A method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury, characterized in that, include: A dynamic structural model is constructed, which is based on a three-layer structure, including a bottom layer, a middle layer, and a top layer. The dynamic structural model is subjected to cyclic ventilation stretching adjustment according to the pneumatic control algorithm. The pneumatic control algorithm is based on PID adjustment algorithm and adaptive respiratory rhythm adjustment algorithm. The PID adjustment algorithm is based on dynamic deformation rate, and the adaptive respiratory rhythm adjustment algorithm is based on ventilation frequency. The dynamic structural model is simulated and optimized to obtain the final dynamic three-dimensional circulating ventilation stretching model.

2. The method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 1, characterized in that, The steps for constructing the dynamic structural model specifically include: constructing a three-layer structure of the dynamic structural model, the three-layer structure including a bottom layer, an intermediate layer, and a top layer; the bottom layer is a PDMS base layer, the PDMS base layer including a gas microchannel structure and a channel chamber structure; the intermediate layer is a cell culture substrate and a deformation generation layer, the intermediate layer undergoing non-planar strain; the top layer is a PDMS capping layer, the PDMS capping layer including a gas path interface and a cell culture chamber, the top layer being a closed gas phase environment, the top layer and the bottom layer being physically isolated, the physical isolation being based on the effect of the intermediate layer; assembling the three-layer structure to obtain the dynamic structural model.

3. The method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 2, characterized in that, The step of assembling the three-layer structure to obtain a dynamic structural model specifically includes: performing plasma treatment on the bottom-middle layer contact surface and the top-middle layer contact surface of the three-layer structure, followed by overnight curing treatment to bond the bottom-middle layer contact surface and the top-middle layer contact surface, wherein the temperature of the overnight curing treatment is kept constant at 65 degrees Celsius; performing alignment and sealing treatment on the three-layer structure to ensure that the three-layer structure is in a gas-liquid isolation state, wherein a stable gas-liquid interface exists in the gas-liquid isolation state; and connecting the bottom and top layers with gas paths to obtain a dynamic structural model.

4. The method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 1, characterized in that, The step of performing cyclic ventilation and stretching adjustment on the dynamic structural model according to the pneumatic control algorithm specifically includes: cyclic ventilation of the dynamic structural model and real-time calculation of the dynamic deformation rate of the intermediate layer. The specific algorithm for the dynamic deformation rate is as follows: ,in, Indicates the dynamic deformation rate. Indicates time, This represents the area of ​​the intermediate layer at the current moment. This represents the original intermediate layer area; the simulated deformation error is calculated based on a preset deformation rate threshold and the dynamic deformation rate. The specific algorithm for calculating the simulated deformation error is as follows: ,in, Indicates the simulated deformation error. This represents a preset deformation rate threshold; PID control is performed based on the simulated deformation error to obtain the regulated air pressure value. The specific algorithm for PID control is as follows: ,in, This indicates the adjustment of the air pressure value. 、 、 The PID coefficient is represented; closed-loop negative feedback regulation is performed based on the adjusted air pressure value; and ventilation modes for different pathological states are simulated based on the adaptive respiratory rhythm algorithm.

5. The method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 4, characterized in that, The step of simulating ventilation modes for different pathological states using an adaptive respiratory rhythm algorithm specifically includes: obtaining the respiratory time for different pathological states to adaptively calculate the ventilation frequency for the ventilation mode simulation. The specific algorithm for the ventilation frequency is as follows: ,in, Indicates ventilation frequency, and These represent the inspiratory and expiratory times, respectively; the timing is adjusted according to the ventilation frequency to perform pneumatic control for long-duration ventilation simulation.

6. The method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 1, characterized in that, The step of simulating and optimizing the dynamic structural model to obtain the final dynamic three-dimensional circulatory ventilation stretching model specifically includes: seeding lung epithelial cells and endothelial cells on the surface of the intermediate layer of the dynamic structural model and setting the dynamic structural model in a periodic aerodynamic state; then transferring macrophages to the bottom layer of the dynamic structural model for co-culture of alveolar-vascular-immune cells; performing inflammatory factor analysis and simulating and optimizing the current dynamic structural model to obtain the final dynamic three-dimensional circulatory ventilation stretching model.

7. A system for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury, characterized in that, include: A building module is used to build a dynamic structural model, which is based on a three-layer structure, including a bottom layer, a middle layer, and a top layer. An adjustment module is used to perform cyclic ventilation stretching adjustment on the dynamic structural model according to a pneumatic control algorithm. The pneumatic control algorithm is based on a PID adjustment algorithm and an adaptive respiratory rhythm adjustment algorithm. The PID adjustment algorithm is based on dynamic deformation rate, and the adaptive respiratory rhythm adjustment algorithm is based on ventilation frequency. The simulation optimization module is used to perform simulation optimization based on the dynamic structural model to obtain the final dynamic three-dimensional circulating ventilation stretching model.

8. The system for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury according to claim 7, characterized in that, The construction module further includes: a three-layer structure for constructing a dynamic structural model, comprising a bottom layer, a middle layer, and a top layer; the bottom layer is constructed based on PDMS casting, and has gas microchannels and four channel chambers, wherein the gas microchannels are 1 mm wide, 15 mm long, and 0.3 mm deep, and the channel chambers are circular holes with a diameter of 35 mm and a depth of 0.3 mm, and the bottom layer has cell transfer slots at its edges; the middle layer is constructed based on PDMS casting and solidification, and is a PDMS elastic membrane with a thickness of 300 μm, wherein the PDMS elastic membrane undergoes non-planar strain under gas pressure, and the deformation rate of the non-planar strain ranges from 5% to 50%; the top layer is constructed based on PDMS casting, and has culture wells and four channel chambers, wherein the channel chambers are circular holes with a diameter of 35 mm and a depth of 0.3 mm.

9. A storage medium, characterized in that, The storage medium stores one or more programs that, when executed by a processor, implement the method for constructing a dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury as described in any one of claims 1-7.

10. A computer device, characterized in that, The computer device includes a memory and a processor, wherein: the memory is used to store computer programs; and the processor is used to execute the computer programs stored in the memory to implement the method for constructing the dynamic three-dimensional circulatory ventilation stretching model of ventilator-induced lung injury as described in any one of claims 1-7.

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