Bioartificial liver system for convective substance exchange

Abstract

The invention discloses a convection type substance exchange bioartificial liver system. A plasma separation channel comprises a plasma separator, an artery pipeline and a vein pipeline; the biological purification passage comprises a first bioreactor, a solid-liquid separator, a pre-purification pipeline for connecting a first inlet of the first bioreactor to a raw plasma outlet of the plasma separator, and a post-purification pipeline for connecting a purification outlet of the first bioreactor to a separation inlet of the solid-liquid separator; the backflow pipeline is connected with a purified plasma outlet of the solid-liquid separator to the vein pipeline; the biological regeneration channel comprises a second bioreactor, a hepatocyte recovery pipeline for connecting a recovery inlet of the second bioreactor to a hepatocyte outlet of the solid-liquid separator, and a biological supply pipeline for connecting a regeneration outlet of the second bioreactor to a second inlet of the first bioreactor; the first inlet and the second inlet face each other in the first bioreactor such that a convective mass exchange state is generated inside the first bioreactor.

Description

Technical Field

[0001] The present application relates to the technical field of medical devices, and in particular to a bioartificial liver system for convective material exchange. Background Art

[0002] The bioartificial liver system can temporarily replace some of the liver's functions, creating conditions for liver cell repair and regeneration in patients with liver failure, and also creating time for waiting for liver transplant donors. However, due to the different types of bioreactors used, the purification effect of plasma varies, and the purification efficiency needs to be improved.

[0003] The hepatocyte suspension bioreactor is an early reactor developed as a bio-artificial liver. The suspended hepatocytes are easy to culture in vitro and can fully exchange substances with plasma. It still has application value, but this technology also has obvious disadvantages. One of them is that the biological activity of suspended hepatocytes is relatively low, and the biological activity will further decline during the passage process. It is difficult for them to self-renew after mixing with plasma for detoxification metabolism. Therefore, the amount of cells used is large but the plasma purification effect is difficult to effectively improve. Summary of the invention

[0004] In view of the shortcomings of the existing methods, the present application proposes a bioartificial liver system with convective material exchange to solve the technical problems of insufficient purification efficiency and large cell consumption in related technologies.

[0005] The present application provides a bioartificial liver system for convective material exchange, which comprises: The plasma separation passage comprises a plasma separator, an arterial line connecting a blood inlet of the plasma separator to a recipient artery, and a venous line connecting a blood cell outlet of the plasma separator to a recipient vein; a biological purification pathway, comprising a first bioreactor, a solid-liquid separator, a pre-purification pipeline connecting a first inlet of the first bioreactor to a raw plasma outlet of the plasma separator, a post-purification pipeline connecting a purification outlet of the first bioreactor to a separation inlet of the solid-liquid separator, and a return pipeline connecting a clean plasma outlet of the solid-liquid separator to the venous pipeline; a biological regeneration pathway, comprising a second bioreactor, a hepatocyte recovery pipeline connecting a recovery inlet of the second bioreactor to a hepatocyte outlet of the solid-liquid separator, and a biological supply pipeline connecting a regeneration outlet of the second bioreactor to a second inlet of the first bioreactor; The first inlet and the second inlet are opposite to each other in the first bioreactor, so that a convective material exchange state is generated inside the first bioreactor.

[0006] Optionally, the solid-liquid separator is a membrane separator and / or a centrifugal separator, which is used to separate the solid phase and the liquid phase from the first bioreactor.

[0007] Furthermore, the biological purification pathway also includes a plasma recovery pipeline connecting the clean plasma outlet of the solid-liquid separator and the third inlet of the first bioreactor.

[0008] Optionally, the clean plasma outlet is provided with a first flow divider to connect the reflux line and the plasma recovery line.

[0009] Optionally, the biological purification path further comprises a body fluid replenishment tank, which merges with the return line or the venous line through a fluid replenishment line.

[0010] Further optionally, the biological regeneration pathway also includes a waste liquid tank connected to the hepatocyte outlet of the solid-liquid separator via a waste liquid pipeline.

[0011] Furthermore, a second diverter is provided at the hepatocyte outlet to connect the hepatocyte recovery pipeline and the waste liquid pipeline.

[0012] Furthermore, the biological regeneration pathway also includes an oxygenator and / or a temperature controller connected to the biological supply pipeline.

[0013] Optionally, the first bioreactor and the second bioreactor are suspended cell bioreactors and / or semi-suspended cell bioreactors, respectively.

[0014] Furthermore, at least one peristaltic pump is respectively arranged on the slurry separation passage, the biological purification passage and the biological regeneration passage.

[0015] The beneficial technical effects brought about by the technical solution provided by the embodiment of the present application include: (1) The bioartificial liver system with convective material exchange of the present application controls the liquid circulation inside the system to form convective turbulence inside the first bioreactor, thereby accelerating the material exchange inside the first bioreactor and fully exerting the plasma purification effect of suspended or semi-suspended hepatocytes; (2) The bioartificial liver system of the present application with convection material exchange adds a second bioreactor to form a biological regeneration pathway, which can replenish the liver cells in the first bioreactor on the one hand, and on the other hand, some of the recovered liver cells have the potential to activate the passage cells, thus preventing the biological activity of the passage cells from declining too quickly; (3) The bioartificial liver system with convective material exchange of the present application has a relatively simple pipeline configuration, and the net plasma and liver cell recovery amount can be controlled by the diverter to maintain the dynamic balance of the system. The regulation is simple, making the operating cost of the system controllable.

[0016] Additional aspects and advantages of the present application will be partially given in the following description, which will become apparent from the following description, or will be understood through the practice of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The above and / or additional aspects and advantages of the present application will become apparent and easily understood from the following description of the embodiments in conjunction with the accompanying drawings, in which: Figure 1 A schematic structural diagram of a bioartificial liver system for convective substance exchange provided in an embodiment of the present application.

[0018] Figure 2 This is a flow chart of the state changes of whole blood in the bioartificial liver system with convective material exchange of the present application. DETAILED DESCRIPTION

[0019] The embodiments of the present application are described below in conjunction with the drawings in the present application. It should be understood that the implementation methods described below in conjunction with the drawings are exemplary descriptions for explaining the technical solutions of the embodiments of the present application and do not constitute a limitation on the technical solutions of the embodiments of the present application.

[0020] Those skilled in the art will appreciate that, unless expressly stated, the "said" and "the" used herein may also include plural forms. It should be further understood that the term "including" used in the specification of the present application refers to the presence of the features, integers, steps, operations, elements and / or components, but does not exclude the implementation of other features, information, data, steps, operations, elements, components and / or combinations thereof supported by the technical field. The term "and / or" used herein refers to at least one of the items defined by the term, for example, "A and / or B" may be implemented as "A", or as "B", or as "A and B".

[0021] In order to make the objectives, technical solutions and advantages of the present application clearer, the implementation methods of the present application will be further described in detail below with reference to the accompanying drawings.

[0022] refer to Figure 1 and Figure 2The bioartificial liver system of convective material exchange of the present application is used to purify the blood of the receptor 1. The system includes a plasma separation passage 2, a biological purification passage 3 and a biological regeneration passage 4 which are interconnected. At least one peristaltic pump 5 is respectively provided on each of the above passages as the power for the flow of liquid. Among them, the plasma separation passage 2 is used to separate the whole blood directly from the receptor 1 into plasma and blood cells, the biological purification passage 3 is used to biologically purify the plasma through suspended hepatocytes, and the biological regeneration passage 4 is used to realize the regeneration cycle of the hepatocytes in the biological purification passage 3. The purified plasma and the previously separated blood cells finally flow back into the body of the receptor 1 to complete the blood purification cycle. The specific structure and working principle of each passage are described in detail below.

[0023] The plasma separation passage 2 includes a plasma separator 21, an arterial line 22 connecting the blood inlet 211 of the plasma separator 21 to the artery of the recipient 1, an arterial line 22 connecting the plasma separator 21, and a venous line 23 connecting the cell outlet of the plasma separator 21 to the vein of the recipient 1. The core part of the plasma separator 21 is the separation chamber, which is usually equipped with a filter membrane with a microporous structure for physically separating blood cells and plasma. Therefore, the plasma separator 21 is provided with a blood inlet 211, a raw plasma outlet 213 and a blood cell outlet 212. In this embodiment, after the arterial blood of the recipient 1 enters the plasma separator 21 through the arterial line 22, the blood cells and plasma are separated through the separation chamber, and the separated plasma flows as the raw plasma to other processing links through the pre-purification line 33 described below, and the intercepted blood cells flow back to the body of the recipient 1 through the venous line 23. In a possible implementation, the arterial line 22 includes an arterial line connected to a blood-drawing deep venous catheter preset in the receptor 1, a puncture head is provided at the end of the arterial line, and a blood pump and an arterial pot are provided on the arterial line. Correspondingly, a blood pump installation position for installing the blood pump is provided on the arterial line, and the arterial pot is provided with three interface connectors, one of which is used to connect a pressure sensor, and the remaining two interface connectors are used to connect the arterial line, so that the arterial line is connected through the arterial pot, and the role of the arterial pot here is mainly to prevent air from entering the subsequent circulation path. The venous line 23 includes a venous line connected to the vein of the receptor 1, and a venous pot with four connectors is provided on the venous line, two of which are used to connect the venous line, so that the venous pot is connected to the venous line; among the remaining two connectors, one connector is used to connect a pressure sensor, and the other connector is used to connect to the return line 35 below. The role of the venous pot here is mainly to prevent air from entering the body of the receptor 1. The specific implementation of the above arterial line 22 and venous line 23 can be optimized and adjusted according to common knowledge, without affecting the essence of the invention of the present application.

[0024] The biological purification pipeline includes a first bioreactor 31 and a solid-liquid separator 32, wherein the first bioreactor 31 is used as a place for biological purification of plasma, and includes a first inlet 311, a second inlet 312, a third inlet 313 and a purification outlet 314; the solid-liquid separator 32 includes a separation inlet 321, a clean plasma outlet 322 and a liver cell outlet 323. It also includes: a pre-purification pipeline 33, connecting the first inlet 311 to the raw plasma outlet 213 of the plasma separator 21, for introducing raw plasma separated by the plasma separator 21; A post-purification pipeline 34 connects the purification outlet 314 to the separation inlet 321 of the solid-liquid separator 32 for subsequent separation of clean plasma through the solid-liquid separator 32; The reflux pipeline 35 connects the clean plasma outlet 322 of the solid-liquid separator 32 to the venous pipeline 23, and is used to merge with the blood cells separated by the plasma separator 21 to form purified whole blood and then be re-injected into the recipient 1.

[0025] In this embodiment, the first bioreactor 31 adopts a suspended cell bioreactor so that liquid plasma can be fully mixed with suspended hepatocytes and their culture medium, so as to improve the degree of material exchange between hepatocytes and plasma. The plasma stays in the first reactor for a sufficient time so that the hepatocytes and their metabolites can eliminate, transform or reduce toxic substances in the plasma. These toxic substances include but are not limited to endotoxins, high bilirubin, other pathological factors and metabolic wastes caused by liver failure. The sufficient time for plasma to stay in the first reactor should be understood as the total residence time. The plasma can enter the first reactor for purification treatment many times, and the effect of gradual purification can be achieved through multiple cycles. There are two ways of multiple cycles adopted in this embodiment: one is to extract whole blood from the body of the recipient 1 for purification treatment many times to maintain the dynamic balance of the blood volume of the recipient 1; the other is to recycle the clean plasma separated by the solid-liquid separator 32 into the first bioreactor 31 for repeated treatment to improve the "cleanliness" of the clean plasma returning to the recipient 1. Corresponding to the second circulation method, this embodiment sets a plasma recovery pipeline 36 connected to the third inlet 313 of the first bioreactor 31 at the clean plasma outlet 322. Furthermore, the clean plasma outlet 322 is provided with a first diverter 39 for connecting the reflux line 35 and the plasma recovery line 36 and for adjusting the flow rates of the reflux line 35 and the plasma recovery line 36 respectively, so as to better realize multiple circulation purification treatment of plasma.

[0026] Considering that part of the clean plasma will flow back to the first bioreactor 31 for circulation, the present embodiment is provided with a body fluid replenishment tank 37, which is joined with the return line 35 through the replenishment line 38, or the replenishment line 38 is joined with the venous line 23, and the artificial body fluid is replenished in time by controlling the flow rate or periodically injecting quantitatively, thereby better maintaining the stability of the vital signs of the recipient 1 during the treatment process. Artificial body fluid theoretically needs to simulate all the components and proportions of body fluid, but in clinical applications, a suitable formula can be adopted according to actual needs, such as compounding some hormones, growth factors or special electrolyte components based on physiological saline.

[0027] In another possible embodiment, the first bioreactor 31 can adopt a semi-suspended cell bioreactor, that is, a stationary phase or filler that can be dispersed in the culture medium is used as a carrier for hepatocytes to adhere to the wall, thereby reducing the effect of the shear force inside the reactor on the adherent cells. This reactor combines the advantages of suspension culture and fixed culture. In this case, after the stationary phase or filler containing hepatocytes reaches the solid-liquid separator 32, it will be separated as a solid phase and a liquid phase of clean plasma. If it is necessary to separate the suspended hepatocytes, it is necessary to introduce a hepatocyte separation module with other working principles.

[0028] In this embodiment, the solid-liquid separator 32 is used to separate the solid phase of liver cells (and their carriers) and the liquid phase of clean plasma. According to the separation method, a membrane separator or a centrifugal separator can be used, and the separated solid phase and liquid phase can be recycled separately. Furthermore, the solid-liquid separator 32 can also add an adsorption separation function to remove non-recoverable substances free in the clean plasma, such as toxic substances or artificial oxygen carriers, to ensure the "cleanliness" of the clean plasma.

[0029] The biological regeneration path 4 includes a second bioreactor 41, which is used as a biological supplementary reservoir for the first bioreactor 31. The second bioreactor 41 includes a recovery inlet 411 and a regeneration outlet 412; and further includes: A hepatocyte recovery pipeline 42 connects the recovery inlet 411 to the hepatocyte outlet 323 of the solid-liquid separator 32, and is used to recover the hepatocytes after the purification process (reacted hepatocytes); The biological replenishment pipeline 43 connects the regeneration outlet 412 to the second inlet 312 of the first bioreactor 31 , and is used to transport hepatocytes with better biological activity (replenishment hepatocytes) and fresh culture medium to the first bioreactor 31 .

[0030] The second bioreactor 41 has the significant function of supplying fresh hepatocytes and culture medium to the first bioreactor 31. In one possible implementation, the input of the reacted hepatocytes into the unreacted hepatocytes may form a benign activation of the unreacted hepatocytes, prompting the unreacted hepatocytes to accumulate active substances to cope with the toxic substances in the original plasma in advance, and avoiding adverse stress of the supplied hepatocytes when entering the microenvironment of the first cell reactor. Another possible implementation is that the input of the reacted hepatocytes into the second bioreactor can be used as supplementary seed cells, which is beneficial to the proliferation of hepatocytes in the second bioreactor and increases the number of proliferation. In addition, the reacted hepatocytes in the fresh culture medium may be affected by other unreacted hepatocytes, which may be beneficial to the recovery of their own biological activity, and the hepatocytes of subsequent passages can be used as supply hepatocytes to participate in the plasma purification process again.

[0031] This embodiment sets up two bioreactors with different functions, which are adapted to the physiological characteristics of liver cells, so that the in vitro proliferation and in vitro metabolism of liver cells do not interfere with each other. Optionally, the first bioreactor 31 can be integrated into the complete equipment of the corresponding bioartificial liver system to reduce interference with the first bioreactor, and the second bioreactor 41 can be connected to the complete equipment of the bioartificial liver system through pipelines to facilitate disassembly or replacement. The pipeline connecting the second bioreactor 41 to the complete system can be the aforementioned liver cell recovery pipeline 42 and biological supply pipeline 43, or it can be connected to the liver cell recovery pipeline 42 and biological supply pipeline 43 through an extended pipeline.

[0032] In this embodiment, the first inlet 311 and the second inlet 312 in the first bioreactor 31 are arranged relative to each other in the tank body, so that the original plasma input from the first inlet 311 and the replenished hepatocytes input from the second inlet 312 can form a convective turbulence inside the first bioreactor 31. The state of the convective turbulence is conducive to the solid-liquid mixture or suspended matter inside the first bioreactor tank to flow more fully, avoiding the blind area of ​​material exchange. In this way, the purification effect of suspended or semi-suspended hepatocytes on plasma can be better exerted.

[0033] In another implementation, the biological regeneration pathway 4 also includes a waste liquid tank 44, which is connected to the hepatocyte outlet 323 of the solid-liquid separator 32 through a waste liquid pipeline 45. Furthermore, a second diverter 46 is provided at the hepatocyte outlet 323 to connect the hepatocyte recovery pipeline 42 and the waste liquid pipeline 45. After the reaction, it is not preferred that all the hepatocytes are recovered and regenerated, so a second diverter 46 is provided to control the recovery ratio, and the remaining unrecovered hepatocytes are drained to the waste liquid tank 44 for temporary storage. In the present application, the waste liquid tank 44 is the only outlet in the closed circulation pipeline. In some cases, the waste liquid tank 44 can serve as a sampling area, and the discarded hepatocytes and their cultures are regularly extracted from the waste liquid tank 44 for detection, which can reflect the operating status of the bioartificial liver system to a certain extent. The separated hepatocytes (and their carriers) discharged from the hepatocyte outlet 323 are actually in a state of solid-liquid mixture, and the liquid is mainly the hepatocyte culture that has not been completely separated. Therefore, the substances discharged through the hepatocyte outlet 323 can be used to detect the content of bioactive markers of hepatocytes, the content of toxic substances in the residual culture medium, the pH value of the culture, the dissolved oxygen content, etc. The above-mentioned detection content can also be at least partially realized by automated detection equipment. At this time, the waste liquid tank 44 can be a part of the automated detection equipment, or it can be the location where the bioartificial liver system of the present application is docked with the automated detection equipment. The second diverter 46 is used to adjust the flow of the hepatocyte recovery pipeline 42 and the waste liquid pipeline 45 respectively to control the amount of hepatocyte recovery.

[0034] The flow distribution parameters of the first flow splitter 39 and the second flow splitter 46 can be set to fixed values, or can be adjusted in a feedback manner according to sensor data in the system. Different types of flow splitters can be selected according to different usage requirements.

[0035] Furthermore, the biological regeneration pathway 4 further includes an oxygenator 47 and / or a temperature controller connected to the biological supply pipeline 43 .

[0036] The temperature controller (not shown) can provide a stable temperature environment for the bioartificial liver system of the present application. When adjusted to a temperature environment close to that in the body, it can avoid unnecessary stress on plasma and blood cells in various circulation pathways and the production of stress products. In addition, the appropriate temperature can also maintain the biological activity of liver cells and provide a more efficient plasma purification effect.

[0037] One possible implementation is to use an oxygenator containing an oxygen carrier47. In the blood purification system, the oxygen carrier mainly involves artificial oxygen carriers, which can simulate the function of natural red blood cells and are used to provide oxygen to the patient in an emergency or when blood transfusion is difficult. The main oxygen carriers currently exist and their use methods are as follows: perfluorocarbon (PFC) oxygen carriers; blood substitutes used in the early days, but due to its many limitations, the widespread clinical application of PFC has been greatly limited. Hemoglobin modified oxygen carriers; classified according to the preparation method as follows: First generation: mainly including intramolecular, intermolecular cross-linking, polymerization, and recombinant hemoglobin; second generation: oxygen carriers characterized by cross-linking certain enzymes; third generation: microencapsulated type; the first and second generation oxygen carriers have oxygen carrying-releasing functions close to natural red blood cells and have been used to a certain extent in clinical practice. However, due to its lack of a cell membrane-like barrier, it has extremely high requirements for the purity of the hemoglobin raw material, and free hemoglobin is easy to interact with many active molecules in the blood, inducing a series of abnormal side reactions. Other blood substitutes; hemoglobin oxygen carriers (HBOC), including polymerized hemoglobin, genetically regulated hemoglobin, and polyethylene glycol (PEG) hemoglobin. These carriers have better stability, do not require blood typing and cross-matching, have a longer circulation half-life, and will not accumulate in related metabolic organs to produce toxicity. The use of the above artificial oxygen carriers can improve the oxygen supply effect of the first bioreactor 31 and the second bioreactor 41, which is beneficial to maintaining or activating the physiological activity of liver cells and enhancing the purification effect of the bioartificial liver of the present application.

[0038] refer to Figure 2 , using the bioartificial liver system of the present application for convective material exchange, the state of the whole blood of the recipient 1 changes as follows: The whole blood is separated into original plasma and blood cells by the plasma separator 21. The blood cells are returned to the body of the recipient 1. The original plasma is transported to the convection material exchange area (first bioreactor 31) to exchange substances with the liver cells. After the reaction is completed, it is transported to the solid-liquid separator 32 to be separated into clean plasma and liver cells after reaction. The clean plasma is divided into two parts, one part of which is returned to the convection material exchange area for re-purification, and the other part is returned to the body of the recipient 1; the liver cells after reaction are also divided into two parts, one part is recycled and regenerated into replenishment liver cells, and the other part becomes waste liver cells. The replenishment liver cells are transported to the convection material exchange area to exchange substances with the original plasma.

[0039] In summary, a bioartificial liver system for convective material exchange includes: a plasma separation pathway, including a plasma separator, an arterial pipeline connecting the blood inlet of the plasma separator to the recipient artery, and a venous pipeline connecting the blood cell outlet of the plasma separator to the recipient vein; a biological purification pathway, including a first bioreactor, a solid-liquid separator, a pre-purification pipeline connecting the first inlet of the first bioreactor to the original plasma outlet of the plasma separator, a post-purification pipeline connecting the purification outlet of the first bioreactor to the separation inlet of the solid-liquid separator, and a reflux pipeline connecting the clean plasma outlet of the solid-liquid separator to the venous pipeline; a biological regeneration pathway, including a second bioreactor, a hepatocyte recovery pipeline connecting the recovery inlet of the second bioreactor to the hepatocyte outlet of the solid-liquid separator, and a biological supply pipeline connecting the regeneration outlet of the second bioreactor to the second inlet of the first bioreactor; the first inlet and the second inlet are opposite to each other in the first bioreactor, so that a convective material exchange state is generated inside the first bioreactor. The bioartificial liver system with convective material exchange of the present application controls the liquid circulation inside the system, forms convective turbulence inside the first bioreactor, accelerates the material exchange inside the first bioreactor, and can give full play to the plasma purification effect of suspended or semi-suspended hepatocytes.

[0040] Those skilled in the art will appreciate that the various operations, methods, steps, measures, and schemes in the processes discussed in this application may be alternated, changed, combined, or deleted. Furthermore, other steps, measures, and schemes in the various operations, methods, and processes discussed in this application may also be alternated, changed, rearranged, decomposed, combined, or deleted. Furthermore, steps, measures, and schemes in the related art that are similar to those disclosed in this application may also be alternated, changed, rearranged, decomposed, combined, or deleted.

[0041] In the description of the present application, the directions or positional relationships indicated by words such as "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" are based on the exemplary directions or positional relationships shown in the accompanying drawings. They are for the convenience of describing or simplifying the description of the embodiments of the present application, and do not indicate or imply that the referred device or component must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be understood as limitations on the present application.

[0042] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, unless otherwise specified, "plurality" means two or more.

[0043] In the description of this application, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in this application can be understood according to specific circumstances.

[0044] In the description of this specification, specific features, structures, materials or characteristics may be combined in an appropriate manner in any one or more embodiments or examples.

[0045] The above is only a partial implementation method of the present application. It should be pointed out that for ordinary technicians in this technical field, without departing from the technical concept of the scheme of the present application, other similar implementation methods based on the technical ideas of the present application are also within the protection scope of the embodiments of the present application.

Claims

1. A bioartificial liver system with convective material exchange, characterized in that: include: The plasma separation passage comprises a plasma separator, an arterial line connecting a blood inlet of the plasma separator to a recipient artery, and a venous line connecting a blood cell outlet of the plasma separator to a recipient vein; a biological purification pathway, comprising a first bioreactor, a solid-liquid separator, a pre-purification pipeline connecting a first inlet of the first bioreactor to a raw plasma outlet of the plasma separator, a post-purification pipeline connecting a purification outlet of the first bioreactor to a separation inlet of the solid-liquid separator, and a return pipeline connecting a clean plasma outlet of the solid-liquid separator to the venous pipeline; a biological regeneration pathway, comprising a second bioreactor, a hepatocyte recovery pipeline connecting a recovery inlet of the second bioreactor to a hepatocyte outlet of the solid-liquid separator, and a biological supply pipeline connecting a regeneration outlet of the second bioreactor to a second inlet of the first bioreactor; The first inlet and the second inlet are opposite to each other in the first bioreactor, so that a convective material exchange state is generated inside the first bioreactor.

2. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The solid-liquid separator is a membrane separator and / or a centrifugal separator, which is used to separate the solid phase and the liquid phase from the first bioreactor.

3. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The biological purification path also includes a plasma recovery pipeline connecting the clean plasma outlet of the solid-liquid separator and the third inlet of the first bioreactor.

4. The bioartificial liver system for convective material exchange according to claim 3, characterized in that: The clean plasma outlet is provided with a first flow divider to connect the reflux pipeline and the plasma recovery pipeline.

5. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The biological purification path also includes a body fluid replenishment tank, which merges with the return line or the venous line through a fluid replenishment line.

6. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The biological regeneration pathway also includes a waste liquid tank, which is connected to the liver cell outlet of the solid-liquid separator through a waste liquid pipeline.

7. The bioartificial liver system for convective material exchange according to claim 6, characterized in that: The hepatocyte outlet is provided with a second diverter to connect the hepatocyte recovery pipeline and the waste liquid pipeline.

8. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The biological regeneration pathway also includes an oxygenator and / or a temperature controller connected to the biological supply line.

9. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: The first bioreactor and the second bioreactor are respectively suspended cell bioreactors and / or semi-suspended cell bioreactors.

10. The bioartificial liver system for convective material exchange according to claim 1, characterized in that: At least one peristaltic pump is respectively arranged on the pulp separation passage, the biological purification passage and the biological regeneration passage.

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