Vascular microcirculation chip and system for in-vitro three-dimensional tissue

Abstract

The invention belongs to the technical field of biochips, and relates to a blood vessel microcirculation chip and system for in-vitro three-dimensional tissue. The blood vessel microcirculation chip of the in-vitro three-dimensional tissue comprises a chip shell component with a culture tank, an in-vitro three-dimensional tissue is arranged in the culture tank, and the in-vitro three-dimensional tissue comprises a matrix, cells in the matrix and a microcirculation vessel network in the matrix; the microcirculation vessel network in the matrix comprises a bionic artery, a bionic vein and a self-development capillary network in the matrix. The in-vitro three-dimensional tissue blood vessel microcirculation chip and system provided by the invention have bionic artery, bionic vein and capillary networks similar to organisms, and simulate the blood vessel microcirculation process of arterial high-pressure exudation mass transfer and oxygen transfer and vein low-pressure reflux metabolism.

Description

Technical Field

[0001] The present invention belongs to the technical field of biochips and relates to a vascular microcirculation chip and system for in vitro three-dimensional tissues. Background Art

[0002] With the continuous development of in vitro biochip technology, its application potential in the field of biological research and pathological and pharmacological analysis has become increasingly prominent. Among them, compared with traditional open-channel organ chips, vascular chips more accurately simulate the in vivo penetration process of drug molecules through the vascular wall, reducing the inaccuracy in drug evaluation experiments caused by the traditional organ chips not considering the role of vascular permeability, and greatly improving the authenticity and reliability of experiments.

[0003] However, most of the vascular structures in current vascular chips are simply single flow channels and do not simulate the vascular microcirculation network structure composed of arteries, veins, and capillary networks in vivo. Therefore, they lack the vascular microcirculation function similar to that in the human body, resulting in insufficient physiological consistency between existing vascular chips and the real in vivo situation. Summary of the Invention

[0004] The present invention provides a vascular microcirculation chip and system for in vitro three-dimensional tissues, which have biomimetic arteries, biomimetic veins, and capillary networks similar to those of organisms, and simulate the vascular microcirculation process of high-pressure exudation of mass transfer and oxygen transfer in arteries and low-pressure reflux metabolism in veins.

[0005] The technical solution of the present invention to solve the above problems is as follows:

[0006] On the one hand, the present invention provides a vascular microcirculation chip for in vitro three-dimensional tissues, which is characterized in that:

[0007] It includes a chip housing component with a culture tank; an in vitro three-dimensional tissue is contained in the culture tank, and the in vitro three-dimensional tissue includes a matrix, cells in the matrix, and a microcirculation vascular network in the matrix; the microcirculation vascular network in the matrix includes biomimetic arteries, biomimetic veins, and a self-developing capillary network in the matrix.

[0008] The function of the chip housing component is to accommodate the in vitro three-dimensional tissue, provide a sealed environment, and provide perfusion interfaces.

[0009] The in vitro three-dimensional tissue refers to a three-dimensional tissue with cell activity formed by a matrix, cells in the matrix, and a microcirculation vascular network in the matrix cultured in vitro.

[0010] The matrix is a gel-like substance with a porous structure composed of biological macromolecules, which is used to provide sites for cells to adhere and develop in three-dimensional space. The cells in the matrix are the active components of the in vitro three-dimensional tissue and the main objects of microcirculation for nutrient supply and metabolism. The microcirculation vascular network in the matrix is the channel for material exchange between the outside of the microcirculation chip and the cells in the matrix. The bionic artery and bionic vein are three-dimensional hollow lumens with a circular cross-section, which can have a single-layer or double-layer wall structure to simulate the multi-layer wall structure of blood vessels in the body, and their axes are continuous straight lines, plane curves or space curves in three-dimensional space. The self-developing capillary network is that the vascular cells in the matrix develop by themselves, grow into a capillary network, and invade and communicate with the bionic artery and bionic vein.

[0011] Furthermore, the matrix is a biocompatible hydrogel composed of one or more of type I collagen, Matrigel matrix glue, fibrin, gelatin, sodium alginate, GelMA, hyaluronic acid, and HAMA.

[0012] Furthermore, the vascular cells in the matrix are one or more of endothelial cells, endothelial cell spheroids, and vascular organoids that have the potential to develop into a capillary network.

[0013] Furthermore, the cells in the matrix may also include one or more of human or animal central nerve cells, peripheral nerve cells, intestinal cells, liver cells, and cardiomyocytes.

[0014] Furthermore, the bionic artery is a circular hollow lumen with an inner diameter of 1.5 - 4 mm, and the bionic artery opens from one side of the matrix and penetrates to the other side of the matrix; the bionic vein is a circular hollow lumen with an inner diameter of 3 mm - 6 mm, and the bionic vein opens from one side of the matrix and penetrates to the other side of the matrix.

[0015] Furthermore, the bionic artery and bionic vein have a single-layer or double-layer porous hydrogel wall structure, where the wall thickness of the bionic artery is 1 - 3 mm, and the wall thickness of the bionic vein is 0.1 - 1.5 mm.

[0016] Furthermore, the walls of the bionic artery and bionic vein contain human or animal endothelial cells; or, the walls of the bionic artery and bionic vein contain a mixture of human endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells; or, the walls of the bionic artery and bionic vein contain a mixture of animal endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells.

[0017] Further, the chip housing component is composed of an upper cover and a lower shell, and the upper cover and the lower shell are encapsulated by threaded fasteners; the lower shell also has four perfusion interfaces for the culture medium to pass through, and the four perfusion interfaces correspond to both ends of the bionic artery and the bionic vein respectively.

[0018] In a second aspect, the present application provides a vascular microcirculation chip system for in vitro three-dimensional tissues, which is characterized in that:

[0019] It includes the above-mentioned vascular microcirculation chip for in vitro three-dimensional tissues, as well as a material tank, a peristaltic pump, a pressure reducing valve, an oxygenator and a filter; the vascular microcirculation chip, the material tank, the peristaltic pump, the pressure reducing valve, the oxygenator and the filter are connected by connecting pipelines.

[0020] The peristaltic pump transfers the culture medium from the material tank to the bionic artery of the microcirculation chip in sequence. After flowing out of the bionic artery, it passes through the pressure reducing valve, flows through the bionic vein, and then passes through the oxygenator and the filter, and finally returns to the material tank.

[0021] The material tank is used to store the culture medium and receive the returned culture medium. The peristaltic pump provides power for the circulation. The pressure reducing valve is used to adjust the fluid pressure entering the bionic vein system. Since the size of the in vitro model cannot fully simulate the in vivo environment, it is difficult to naturally form an arteriovenous pressure difference similar to that in the body. In order to achieve the purpose of simulating the arteriovenous pressure difference in the body, the regulation of the fluid pressure is achieved by installing a pressure reducing valve. The oxygenator is used to process the culture medium flowing out of the bionic vein system of the vascular chip. The filter is specifically configured to filter out the waste generated during the metabolic process and various impurities mixed in it.

[0022] Further, a pressure sensor is connected to the outlet of the peristaltic pump. When the microcirculation chip system operates stably, the outlet pressure of the peristaltic pump is 0.005 Mpa - 0.02 Mpa.

[0023] Further, the outlet pressure of the pressure reducing valve is 10% - 30% of the inlet pressure.

[0024] Further, the oxygenator is a membrane oxygenator.

[0025] Further, the filter is a 0.22 μm needle filter.

[0026] Further, the connecting pipeline is made of silicone or rubber hose with an inner tube diameter of 2 - 5 mm.

[0027] Advantages of the present invention:

[0028] 1. The in vitro three-dimensional tissue vascular microcirculation chip proposed by the present invention successfully replicates the fine structure of in vivo vascular microcirculation, including the complete system of arteries, veins, and capillary networks. This chip not only accurately simulates the anatomical structure of in vivo microcirculation but also deeply mimics the physiological process of blood carrying out material exchange and metabolism through osmosis, improving the physiological consistency of the model and providing a more accurate and reliable in vitro model for the fields of pathology and pharmacology research.

[0029] 2. The in vitro three-dimensional tissue vascular microcirculation chip system proposed by the present invention simulates the circulation process in vivo where arteries have high-pressure fluid rich in oxygen and veins have low-pressure fluid for blood recovery, and has the ability to stably operate in vitro for a long time. This system uses a pressure reducing valve to regulate the fluid pressure in the vein to ensure a reasonable fluid pressure difference between the artery and the vein in a small-sized in vitro model. At the same time, the oxygenator integrated in the system ensures the constant content of oxygen and carbon dioxide in the circulating culture medium. In addition, through the integrated filter, the system can continuously remove the waste and impurities generated by metabolism, ensuring the purity and stability of the environment, providing technical support for simulating the vascular microcirculation process in vitro. Brief Description of the Drawings

[0030] Figure 1 is the structural diagram of a vascular microcirculation chip for an in vitro three-dimensional tissue proposed by the present invention;

[0031] Figure 2 is the structural diagram of the in vitro three-dimensional tissue vascular microcirculation chip system proposed by the present invention;

[0032] Figure 3 is Figure 2 the cross-sectional view in the A-A direction in

[0033] Figure 4 is the structural diagram of another vascular microcirculation chip for an in vitro three-dimensional tissue proposed by the present invention.

[0034] In the figure, 1. upper cover, 2. lower shell, 3. in vitro three-dimensional tissue, 4. bionic vein, 5. matrix, 6. self-developing capillary network, 7. bionic artery, 8. vascular microcirculation chip, 9. oxygenator, 10. filter, 11. material tank, 12. peristaltic pump, 13. pressure reducing valve, 14. pressure sensor. Detailed Embodiments

[0035] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention. Therefore, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the claimed present invention, but merely represents selected embodiments of the present invention.

[0036] Referring to Figure 1 , the present invention provides a vascular microcirculation chip for in vitro three-dimensional tissues, which includes a chip housing component. A culture tank is provided inside the chip housing component, and an in vitro three-dimensional tissue 3 is placed in the culture tank. The in vitro three-dimensional tissue 3 includes a matrix 5, cells in the matrix 5, and a microcirculation vascular network in the matrix 5; the microcirculation vascular network in the matrix 5 includes a bionic artery 7, a bionic vein 4, and a self-developed capillary network 6. Both the bionic artery 7 and the bionic vein 4 are hollow lumens that penetrate both ends of the matrix 5; the self-developed capillary network 6 is a microvascular network self-developed by vascular cells in the matrix 5, and the self-developed capillary network 6 is fused and connected to the bionic artery 7 and the bionic vein 4.

[0037] The function of the chip housing component is to accommodate the in vitro three-dimensional tissue, provide a sealed environment, and provide a perfusion interface.

[0038] The in vitro three-dimensional tissue 3 refers to a three-dimensional tissue with cell activity cultured in vitro, which is composed of a matrix 5, cells in the matrix 5, and a microcirculation vascular network in the matrix 5.

[0039] The matrix 5 is a gel-like substance with a porous structure composed of biological macromolecules, and is used to provide sites for cells to adhere and develop in three-dimensional space.

[0040] The cells in the matrix 5 are used to constitute the cell active components of the in vitro three-dimensional tissue, and are the main objects of microcirculation to supply nutrition and metabolism.

[0041] The microcirculation vascular network in the matrix 5 is a channel for material exchange between the outside of the microcirculation chip and the cells in the matrix.

[0042] The bionic artery 7 and the bionic vein 4 are three-dimensional hollow lumens that penetrate from one side of the matrix 5 to the opposite side. Their cross-sections are circular and can have a single-layer or double-layer wall structure to simulate the multi-layer wall structure of blood vessels in the body. Their axes are continuous straight lines, planar curves, or space curves in three-dimensional space. Among them, the bionic artery 7 is used to transport a culture medium with high pressure, high oxygen, and high nutrition. Under the action of a pressure difference, it penetrates into the matrix pores through the porous tube wall or through the self-developed capillary network 6 connected to it, providing nutrients for the cells in the matrix 5 to simulate the mass transfer function of the artery. The bionic vein 4 is used to return the fluid in the bionic artery and the self-developed capillary network 6, and has a relatively lower pressure than the bionic artery 7. The metabolic wastes of the cells in the matrix 5 penetrate into the bionic vein wall from the matrix 5 or flow into it from the self-developed capillary network 6 under the action of the pressure difference and concentration to simulate the function of venous metabolic wastes and carbon dioxide. The bionic artery 7 and the bionic vein 4 can be realized by embedded coaxial 3D printing or by externally manufacturing blood vessels and then embedding them in an uncrosslinked matrix and crosslinking them later.

[0043] The self-developed capillary network 6 is formed by the blood vessel cells in the matrix 5 growing into a capillary network through self-development and invading and connecting with the bionic artery and the bionic vein.

[0044] In a possible implementation, the matrix 5 is a gel-like substance with a porous structure composed of biological macromolecules. Specifically, the matrix 5 can be a biocompatible hydrogel composed of one or a mixture of type I collagen, Matrigel matrix glue, fibrin, gelatin, sodium alginate, GelMA, hyaluronic acid, HAMA, etc.

[0045] In a possible implementation, the blood vessel cells in the matrix 5 are one or more of endothelial cells, endothelial cell spheroids, and vascular organoids that have the potential to develop into a capillary network.

[0046] In a possible implementation, the cells in the matrix 5 are one or more of human or animal central nerve cells, peripheral nerve cells, intestinal cells, liver cells, and myocardial cells.

[0047] In a possible implementation, see Figure 1 and Figure 3 The bionic artery 7 is a continuous three-dimensional hollow lumen that opens from one side of the matrix 5 and penetrates to the other side of the matrix 5. Its axial cross-section is a circle with a diameter of 1.5 mm - 4 mm, and its axis is a continuous straight line, planar curve, or space curve. The bionic vein 4 is a continuous three-dimensional hollow lumen that opens from one side of the matrix 5 and penetrates to the other side of the matrix 5. Its axial cross-section is a circle with a diameter of 3 mm - 6 mm, and its axis is a continuous straight line, planar curve, or space curve.

[0048] In a possible implementation, the bionic artery 7 and the bionic vein 4 have a single-layer or double-layer porous hydrogel tube wall structure, where the wall thickness of the bionic artery 7 is 1-3 mm, and the wall thickness of the bionic vein 4 is 0.1-1.5 mm.

[0049] In a possible implementation, the tube walls of the bionic artery 7 and the bionic vein 4 contain endothelial cells of humans or animals; alternatively, the tube walls of the bionic artery 7 and the bionic vein 4 contain a mixture of human endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells; alternatively, the tube walls of the bionic artery 7 and the bionic vein 4 contain a mixture of animal endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells.

[0050] In a possible implementation, see Figure 1 , the chip housing component includes an upper cover 1 and a lower shell 2, and the upper cover 1 is encapsulated on the lower shell 2 through threaded fasteners; four perfusion interfaces for the culture medium to pass through are provided on the side wall of the lower shell 2, and the perfusion interfaces correspond to the openings on the bionic artery 7 and the bionic vein 4.

[0051] Example 1:

[0052] Taking the vascular microcirculation chip of an in vitro three-dimensional tissue with central nerve cells as cells in the matrix as an example, the structure of the vascular microcirculation chip 8 is as Figure 1 shown: The vascular microcirculation chip includes a chip housing component and an in vitro three-dimensional tissue 3 inside the chip housing.

[0053] The chip housing component is composed of a transparent upper cover 1 made of PMMA material and a lower shell 2 made of PDMS material. There is a culture tank with a size of 10 mm * 10 mm * 8 mm inside the lower shell, and the in vitro three-dimensional tissue 3 that completely matches the size of the culture tank is inside the culture tank; there are two perfusion interfaces on each of the opposite side walls of the lower shell 2, and the four perfusion interfaces can insert standard stainless steel needles.

[0054] The in vivo three-dimensional tissue 3 is composed of a matrix 5, primary rat neurons in the matrix 5, and a microcirculation vascular network.

[0055] The matrix 5 used is type I collagen hydrogel formed by temperature cross-linking of a type I collagen solution with a concentration of 2 mg / ml.

[0056] The microcirculation vascular network in the matrix 5 includes a bionic artery 7, a bionic vein 4, and a self-developing capillary network 6. The bionic artery 7 is a 0.5% sodium alginate single-layer hollow lumen with a wall thickness of 1 mm and an inner diameter of 2 mm constructed by embedded coaxial 3D printing. The axis is a straight line running through both ends of the matrix, and the inner part of the single-layer tube wall includes mouse brain microvascular endothelial cells (BEND3); the bionic vein 4 is a 0.25% sodium alginate single-layer hollow lumen with a wall thickness of 0.2 mm and an inner diameter of 3 mm constructed by embedded coaxial 3D printing. The axis is a straight line running through both ends of the matrix, and the inner part of the single-layer tube wall includes mouse brain microvascular endothelial cells (BEND3); the self-developing capillary network 6 is formed by mixing human umbilical vein HUVEC at a final concentration of 4*10 6 into the type I collagen hydrogel precursor in the matrix, incubating for a period of time, and using the migration, invasion, and angiogenesis ability of HUVEC to form a microvascular network connected to the bionic artery 7 and the bionic vein 4.

[0057] In addition, referring to Figure 2 , the present invention also proposes a vascular microcirculation chip system for an in vitro three-dimensional tissue, including the above-mentioned vascular microcirculation chip 8 for an in vitro three-dimensional tissue, as well as a material tank 11, a peristaltic pump 12, a pressure reducing valve 13, an oxygenator 9, and a filter 10. The vascular microcirculation chip, the material tank 11, the peristaltic pump 12, the pressure reducing valve 13, the oxygenator 9, and the filter 10 are connected through connecting pipelines.

[0058] The peristaltic pump 12 transfers the culture medium from the material tank 11 to the bionic artery 7 in sequence. After flowing out of the bionic artery 7, it passes through the pressure reducing valve 13, flows through the bionic vein 4, and then passes through the oxygenator 9 and the filter 10, and finally returns to the material tank 11.

[0059] Referring to Figure 2 , a pressure sensor 14 is connected to the outlet of the peristaltic pump 12. When the microcirculation chip system operates stably, the outlet pressure of the peristaltic pump 12 is 0.005 Mpa - 0.02 Mpa.

[0060] Specifically, the outlet pressure of the pressure reducing valve 13 is 10% - 30% of the inlet pressure; the oxygenator 9 is a membrane oxygenator 9; the filter 10 is a 0.22 μm needle filter; the connecting pipeline uses a silicone or rubber hose with an inner tube diameter of 2 - 6 mm.

[0061] Example 2:

[0062] A vascular microcirculation chip system for an in vitro three-dimensional tissue, as Figure 2 shown, includes the above-mentioned vascular microcirculation chip 8 for an in vitro three-dimensional tissue, a material tank 11, a peristaltic pump 12, a pressure reducing valve 13, an oxygenator 9, a filter 10, and a silicone hose with an inner diameter of 2 mm as the connecting pipeline. The silicone hose is connected to the perfusion interface of the vascular microcirculation chip through a G15 stainless steel needle.

[0063] The endothelial cell medium and the mouse primary neuron medium are mixed in a ratio of 1:1 and added to the feed tank 11. The medium flows out of the feed tank 11, passes through the peristaltic pump 12, then through the pressure sensor 14. By adjusting the flow rate of the peristaltic pump 12, the reading of the pressure sensor 14 is made to be 0.005 MPa, and then it flows into the bionic artery of the vascular microcirculation chip. A part of the medium directly flows into the pores of the matrix hydrogel through osmosis, and another part flows into the self-developed capillary network 6 from the connection between the bionic artery and the self-developed capillary, and penetrates into the matrix through the capillary wall to provide nutrients for the mouse primary neurons. The medium flowing out of the bionic artery passes through the diaphragm pressure reducing valve 13. The diaphragm pressure reducing valve 13 adjusts the outlet pressure to 25% of the inlet pressure, and then the medium flows into the bionic vein 4 to form a pressure difference between the artery and the vein. Under the action of the pressure difference, a part of the medium flows back into the bionic vein 4 from the connection between the self-developed capillary network 6 and the bionic vein 4, or directly penetrates into the bionic vein 4 through the wall of the bionic vein 4. Subsequently, the fluid flowing out of the bionic vein 4 passes through the membrane oxygenator 9 to reduce the partial pressure of carbon dioxide in the medium to 35 mmHg and increase the partial pressure of oxygen in the medium to 80 mmHg to ensure the supply of oxygen and the stability of the pH value of the culture environment, and passes through the 0.22 μm filter 10 to filter impurities and metabolic wastes, and finally flows back to the feed tank to form a complete circulation loop.

[0064] Example 3:

[0065] The difference between this example and Example 1 is as follows. Refer to Figure 4 , the axes of the bionic artery 7 and the bionic vein 4 are continuous spatial spiral lines that penetrate from one side of the matrix to the opposite side of the matrix. Specifically, the bionic artery 7 and the bionic vein 4 can be arbitrarily distributed in three-dimensional space, not just on a single plane, but can be a three-dimensional space curve. For thicker tissues, compared with the straight blood vessels in Example 1, the longitudinal range covered by the spatial spiral blood vessels in this example is larger, and the overall area that can achieve microcirculation mass transfer is also larger, which is helpful for better nutrient supply and waste metabolism of the in vitro three-dimensional tissue.

[0066] The above are only the embodiments of the present invention, and do not limit the protection scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the specification and drawings of the present invention, or directly or indirectly applied to other related system fields, shall be included in the protection scope of the present invention by the same token.

Claims

1. A vascular microcirculation chip for in vitro three-dimensional tissue, characterized in that: It includes a chip housing component, and a culture groove is provided inside the chip housing component, and an in vitro three-dimensional tissue (3) is contained in the culture groove; The in vitro three-dimensional tissue (3) includes a matrix (5), cells in the matrix (5), and a microcirculation vascular network in the matrix (5); The microcirculation vascular network in the matrix (5) includes a bionic artery (7), a bionic vein (4), and a self-developing capillary network (6); Both the bionic artery (7) and the bionic vein (4) are hollow lumens that penetrate both ends of the matrix (5); the self-developing capillary network (6) is a microvascular network self-developed by vascular cells in the matrix (5), and the self-developing capillary network (6) is fused and connected to the bionic artery (7) and the bionic vein (4).

2. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 1, characterized in that: The matrix (5) is a gel-like substance with a porous structure composed of biological macromolecules.

3. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 1, characterized in that: The vascular cells in the matrix (5) are one or more of endothelial cells, endothelial cell spheroids, and vascular organoids having the potential to develop into a capillary network.

4. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 1, characterized in that: The cells in the matrix (5) are one or more of human or animal central nerve cells, peripheral nerve cells, intestinal cells, liver cells, and myocardial cells.

5. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 1, characterized in that: The bionic artery (7) is a continuous three-dimensional hollow lumen that opens from one side of the matrix (5) and penetrates to the other side of the matrix (5), and its axial cross-section is a circle with a diameter of 1.5 mm - 4 mm, and the axis is a continuous straight line, plane curve, or space curve; The bionic vein (4) is a continuous three-dimensional hollow lumen that opens from one side of the matrix (5) and penetrates to the other side of the matrix (5), and its axial cross-section is a circle with a diameter of 3 mm - 6 mm, and the axis is a continuous straight line, plane curve, or space curve.

6. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 5, characterized in that: The bionic artery (7) and the bionic vein (4) have a single-layer or double-layer porous hydrogel tube wall structure, wherein the wall thickness of the bionic artery (7) is 1 - 3 mm, and the wall thickness of the bionic vein (4) is 0.1 - 1.5 mm.

7. The vascular microcirculation chip for in vitro three-dimensional tissue according to claim 6, characterized in that: The tube walls of the bionic artery (7) and the bionic vein (4) contain human or animal endothelial cells; or, the tube walls of the bionic artery (7) and the bionic vein (4) contain a mixture of human endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells; or, the tube walls of the bionic artery (7) and the bionic vein (4) contain a mixture of animal endothelial cells and one or more of pericytes, fibroblasts, and smooth muscle cells.

8. An in vitro three-dimensional tissue vascular microcirculation chip according to claim 1, characterized in that: The chip housing component includes an upper cover (1) and a lower shell (2), and the upper cover (1) is encapsulated on the lower shell (2) through threaded fasteners; four perfusion interfaces for the medium to pass through are provided on the side wall of the lower shell (2), and the perfusion interfaces correspond to the openings on the bionic artery (7) and the bionic vein (4).

9. An in vitro three-dimensional tissue vascular microcirculation chip system, characterized in that: It includes the in vitro three-dimensional tissue vascular microcirculation chip according to any one of claims 1-8, as well as a material tank (11), a peristaltic pump (12), a pressure reducing valve (13), an oxygenator (9) and a filter (10); The vascular microcirculation chip, the material tank (11), the peristaltic pump (12), the pressure reducing valve (13), the oxygenator (9) and the filter (10) are connected through connecting pipelines; The peristaltic pump (12) transfers the culture medium from the material tank (11) to the bionic artery (7) in sequence. After flowing out of the bionic artery (7), it passes through the pressure reducing valve (13), flows through the bionic vein (4), and then passes through the oxygenator (9) and the filter (10), and finally returns to the material tank (11).

10. An in vitro three-dimensional tissue vascular microcirculation chip system according to claim 9, characterized in that: A pressure sensor (14) is connected to the outlet of the peristaltic pump (12). When the microcirculation chip system operates stably, the outlet pressure of the peristaltic pump (12) is 0.005 Mpa - 0.02 Mpa; the outlet pressure of the pressure reducing valve (13) is 10% - 30% of the inlet pressure; the oxygenator (9) is a membrane oxygenator (9); the filter (10) is a needle filter; the connecting pipeline is made of silicone or rubber hose with an inner diameter of the tube.

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