A bioartificial liver system for convective mass exchange

Abstract

This application discloses a convective material exchange bioartificial liver system: a plasma separation pathway including a plasma separator, an arterial line, and a venous line; a biological purification pathway including a first bioreactor, a solid-liquid separator, a pre-purification line connecting the first inlet of the first bioreactor to the original plasma outlet of the plasma separator, a post-purification line connecting the purified outlet of the first bioreactor to the separation inlet of the solid-liquid separator, and a return line connecting the net plasma outlet of the solid-liquid separator to the venous line; and a biological regeneration pathway including a second bioreactor, a hepatocyte recovery line connecting the recovery inlet of the second bioreactor to the hepatocyte outlet of the solid-liquid separator, and a biological supply line 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 each other in the first bioreactor, thereby creating a convective material exchange state inside the first bioreactor.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to a bioartificial liver system with convective mass exchange. Background Technology

[0002] Bioartificial liver systems can temporarily replace some of the liver's functions, creating conditions for hepatocyte repair and regeneration in patients with liver failure, and also buying time while waiting for a liver transplant donor. However, due to the different types of bioreactors used, the plasma purification effect varies, and the purification efficiency needs to be improved.

[0003] The hepatocyte suspension bioreactor is an early development of a bio-artificial liver. Suspended hepatocytes are easy to culture in vitro and can fully exchange substances with plasma, and it still has application value. However, this technology also has obvious drawbacks. One of them is that the biological activity of suspended hepatocytes is relatively low, and the biological activity will further decline during passage. After being mixed with plasma for detoxification and metabolism, they are difficult to renew themselves. Therefore, a large number of cells are used, but the plasma purification effect is difficult to improve effectively. Summary of the Invention

[0004] This application addresses the shortcomings of existing methods by proposing a convective material exchange bioartificial liver system to solve the technical problems of insufficient purification efficiency and large cell usage in related technologies.

[0005] This application provides a bioartificial liver system for convective mass exchange, comprising:

[0006] The plasma separation pathway includes a plasma separator, an arterial conduit connecting the blood inlet of the plasma separator to the recipient artery, and a venous conduit connecting the blood cell outlet of the plasma separator to the recipient vein.

[0007] The biological purification pathway includes a first bioreactor, a solid-liquid separator, a pre-purification pipeline connecting the first inlet of the first bioreactor to the raw plasma outlet of the plasma separator, a post-purification pipeline connecting the purified outlet of the first bioreactor to the separation inlet of the solid-liquid separator, and a return pipeline connecting the purified plasma outlet of the solid-liquid separator to the venous pipeline.

[0008] The biological regeneration pathway includes 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.

[0009] The first inlet and the second inlet are opposite each other in the first bioreactor, which causes a convective mass exchange state to occur inside the first bioreactor.

[0010] Alternatively, the solid-liquid separator may be a membrane separator and / or a centrifugal separator for separating the solid phase and liquid phase originating from the first bioreactor.

[0011] 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.

[0012] Optionally, the net plasma outlet is provided with a first diverter connecting the return pipeline and the plasma recovery pipeline.

[0013] Alternatively, the biological purification pathway may further include a body fluid replenishment tank, which merges with the return pipeline or venous pipeline via a replenishment pipeline.

[0014] Alternatively, the bioregeneration pathway may further include a waste liquid tank connected to the hepatocyte outlet of the solid-liquid separator via a waste liquid pipeline.

[0015] Furthermore, the hepatocyte outlet is equipped with a second diverter connecting the hepatocyte recovery pipeline and the waste liquid pipeline.

[0016] Furthermore, the bioregeneration pathway also includes an oxygenator and / or a temperature controller connected to the bio-supply pipeline.

[0017] Alternatively, the first bioreactor and the second bioreactor may be respectively a suspended cell bioreactor and / or a semi-suspended cell bioreactor.

[0018] Furthermore, at least one peristaltic pump is installed on each of the pulping pathway, the biological purification pathway, and the biological regeneration pathway.

[0019] The beneficial technical effects of the technical solutions provided in this application include:

[0020] (1) The bioartificial liver system of the present application with convective material exchange forms convective turbulence inside the first bioreactor by controlling the liquid circulation inside the system, thereby accelerating the material exchange inside the first bioreactor and fully utilizing the plasma purification effect of suspended or semi-suspended liver cells.

[0021] (2) The bioartificial liver system of the convective material exchange of this application adds a second bioreactor to form a biological regeneration pathway. On the one hand, it can replenish the liver cells in the first bioreactor. On the other hand, some of the recovered liver cells have the potential to activate passaged cells, thus avoiding the rapid decline of the biological activity of passaged cells.

[0022] (3) The bioartificial liver system of the convective material exchange of this application has a simple pipeline setup, and the system can maintain dynamic balance by controlling the amount of net plasma and liver cell recovery through the shunt. The system is easy to regulate and the operating cost is controllable.

[0023] Additional aspects and advantages of this application will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of this application. Attached Figure Description

[0024] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein:

[0025] Figure 1 This is a schematic diagram of a bioartificial liver system for convective mass exchange provided in an embodiment of this application.

[0026] Figure 2 This is a flowchart illustrating the state changes that occur within the bioartificial liver system of whole blood using convective material exchange as described in this application. Detailed Implementation

[0027] The embodiments of this application are described below with reference to the accompanying drawings. It should be understood that the embodiments described below with reference to the accompanying drawings are exemplary descriptions for explaining the technical solutions of the embodiments of this application, and do not constitute a limitation on the technical solutions of the embodiments of this application.

[0028] Those skilled in the art will understand that, unless specifically stated otherwise, the terms "described" and "the" as used herein may also include plural forms. It should be further understood that the term "comprising" as used in the specification of this application means the presence of the stated features, integers, steps, operations, elements, and / or components, but does not exclude other features, information, data, steps, operations, elements, components, and / or combinations thereof supported by the art. The term "and / or" as used herein refers to at least one of the items defined by the term; for example, "A and / or B" can be implemented as "A," or as "B," or as "A and B."

[0029] To make the objectives, technical solutions, and advantages of this application clearer, the embodiments of this application will be described in further detail below with reference to the accompanying drawings.

[0030] refer to Figure 1 and Figure 2The convective material exchange bioartificial liver system of this application is used for blood purification of recipient 1. The system includes interconnected plasma separation pathway 2, biopurification pathway 3, and bioregeneration pathway 4. At least one peristaltic pump 5 is installed in each pathway to drive the fluid flow. Specifically, plasma separation pathway 2 separates whole blood directly from recipient 1 into plasma and blood cells; biopurification pathway 3 uses suspended hepatocytes to biopurify the plasma; and bioregeneration pathway 4 regenerates and recycles the hepatocytes in biopurification pathway 3. The purified plasma and the previously separated blood cells are then returned to recipient 1, completing the blood purification cycle. The specific structure and working principle of each pathway are detailed below.

[0031] The plasma separation pathway 2 includes a plasma separator 21, an arterial conduit 22 connecting the blood inlet 211 of the plasma separator 21 to the artery of recipient 1, an arterial conduit 22 connecting the plasma separator 21, and a venous conduit 23 connecting the cell outlet of the plasma separator 21 to the vein of recipient 1. The core part of the plasma separator 21 is the separation chamber, which is typically equipped with a filter membrane with a microporous structure for physically separating blood cells and plasma. Thus, the plasma separator 21 has a blood inlet 211, a raw plasma outlet 213, and a blood cell outlet 212. In this embodiment, after the arterial blood of recipient 1 enters the plasma separator 21 via the arterial conduit 22, the blood cells and plasma are separated through the separation chamber. The separated plasma, as raw plasma, flows to other processing stages through the pre-purification conduit 33 described below, while the intercepted blood cells flow back into recipient 1 through the venous conduit 23. In one possible implementation, the arterial conduit 22 includes an arterial catheter connected to a pre-installed deep vein catheter within the recipient 1. The arterial catheter has a puncture head at its end and is equipped with a blood pump and an arterial reservoir. Correspondingly, the arterial catheter has a blood pump mounting position for mounting the blood pump. The arterial reservoir has three connectors: one connector for connecting a pressure sensor, and the remaining two connectors for connecting the arterial catheter, allowing the arterial catheter to be connected via the reservoir. The reservoir's primary function is to prevent air from entering the subsequent circulatory pathway. The venous conduit 23 includes a venous catheter connected to a vein in the recipient 1. The venous catheter has a venous reservoir with four connectors: two connectors for connecting the venous catheter, allowing the reservoir to connect to the venous catheter; and of the remaining two connectors, one connector is for connecting a pressure sensor, and the other is for connecting to the return conduit 35 described below. The venous reservoir's primary function is to prevent air from entering the recipient 1. The specific implementations of the arterial conduit 22 and venous conduit 23 can be optimized and adjusted based on common knowledge without affecting the inventive essence of this application.

[0032] The biological purification pipeline includes a first bioreactor 31 and a solid-liquid separator 32. The first bioreactor 31, serving as the site for biologically purifying plasma, includes a first inlet 311, a second inlet 312, a third inlet 313, and a purified outlet 314. The solid-liquid separator 32 includes a separation inlet 321, a purified plasma outlet 322, and a hepatocyte outlet 323. It also includes:

[0033] The pre-purification pipeline 33 connects the first inlet 311 to the raw plasma outlet 213 of the plasma separator 21, and is used to introduce the raw plasma separated by the plasma separator 21.

[0034] After purification, the pipeline 34 is connected to the purification outlet 314 to the separation inlet 321 of the solid-liquid separator 32, which is used to separate the purified plasma through the solid-liquid separator 32.

[0035] The return line 35 connects the net plasma outlet 322 of the solid-liquid separator 32 to the venous line 23, and is used to combine the blood cells separated from the plasma separator 21 into purified whole blood for re-infusion into the recipient 1.

[0036] In this embodiment, the first bioreactor 31 is a suspended cell bioreactor, which allows the liquid plasma to mix thoroughly with the suspended hepatocytes and their culture medium, improving the exchange of substances between the hepatocytes and plasma. The plasma resides in the first reactor for a sufficient time to allow the hepatocytes and their metabolites to eliminate, transform, or reduce toxic substances in the plasma. These toxic substances include, but are not limited to, endotoxins, high bilirubin levels, other pathological factors, and metabolic waste products caused by liver failure. The sufficient time for plasma to reside in the first reactor should be understood as the total residence time. The plasma can enter the first reactor multiple times for purification, achieving a gradual purification effect through multiple cycles. This embodiment employs two methods of multiple cycles: firstly, repeatedly drawing whole blood from the recipient 1 for purification to maintain the dynamic balance of the recipient 1's blood volume; secondly, partially recovering the purified plasma separated by the solid-liquid separator 32 back into the first bioreactor 31 for repeated processing, improving the "cleanliness" of the purified plasma returning to the recipient 1. Corresponding to the second cycle method, this embodiment provides a plasma recovery pipeline 36 connected to the third inlet 313 of the first bioreactor 31 at the purified plasma outlet 322. Furthermore, the purified plasma outlet 322 is equipped with a first diverter 39, which is used to connect the return line 35 and the plasma recovery line 36, and to adjust the flow rates of the return line 35 and the plasma recovery line 36 respectively, so as to better realize the multiple circulation purification treatment of plasma.

[0037] Considering that some of the purified plasma will be returned to the first bioreactor 31 for circulation, this embodiment includes a body fluid replenishment tank 37. The body fluid replenishment tank 37 connects to the return line 35 via a replenishment line 38, or to the intravenous line 23 via the replenishment line 38. By controlling the flow rate or periodically injecting quantitative amounts of artificial body fluid, timely replenishment of artificial body fluid can be achieved, thereby better maintaining the stability of the recipient's vital signs during treatment. Theoretically, the artificial body fluid needs to simulate all components and proportions of body fluids; however, in clinical applications, appropriate formulations can be used according to actual needs, such as a base of physiological saline mixed with hormones, growth factors, or special electrolyte components.

[0038] In another possible implementation, the first bioreactor 31 can be a semi-suspension cell bioreactor, which utilizes a stationary phase or packing material that can be dispersed in the culture medium as a carrier for hepatocyte adhesion, thereby reducing the impact of shear forces inside the reactor on the adherent cells. This type of reactor combines the advantages of suspension culture and fixed culture. In this case, after the stationary phase or packing material containing hepatocytes reaches the solid-liquid separator 32, it will be separated as a solid phase from the net plasma in the liquid phase. If it is necessary to further separate the suspended hepatocytes, a hepatocyte separation module with a different operating principle needs to be introduced.

[0039] In this embodiment, the solid-liquid separator 32 is used to separate the solid phase of hepatocytes (and their carriers) and the liquid phase of purified plasma. Depending on the separation method, a membrane separator or a centrifugal separator can be used. The separated solid and liquid phases can be recycled separately. Furthermore, the solid-liquid separator 32 can also be equipped with an adsorption separation function to remove non-recoverable substances, such as toxic substances or artificial oxygen carriers, from the purified plasma, ensuring the "cleanliness" of the purified plasma.

[0040] Biological regeneration pathway 4 includes a second bioreactor 41, which serves as a biological replenishment reservoir for the first bioreactor 31. The second bioreactor 41 includes a recovery inlet 411 and a regeneration outlet 412; it also includes:

[0041] The 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 hepatocytes that have participated in the purification process (reacted hepatocytes).

[0042] The biological supply pipeline 43 connects the regeneration outlet 412 to the second inlet 312 of the first bioreactor 31, and is used to deliver hepatocytes with better biological activity (supply hepatocytes) and fresh culture medium to the first bioreactor 31.

[0043] The significant role of the second bioreactor 41 is to replenish the first bioreactor 31 with fresh hepatocytes and culture medium. One possible implementation is to introduce post-reacted hepatocytes into unreacted hepatocytes, potentially activating the unreacted cells and encouraging them to accumulate active substances to counteract toxic substances in the original plasma, thus preventing adverse stress on the replenished hepatocytes in the microenvironment of the first bioreactor. Another possible implementation is to introduce post-reacted hepatocytes into the second bioreactor as supplementary seed cells, promoting hepatocyte proliferation and increasing the number of cells proliferating within the second bioreactor. Furthermore, the post-reacted hepatocytes, in fresh culture medium, may benefit from the influence of other unreacted hepatocytes, potentially aiding in the recovery of their biological activity. Subsequent passaged hepatocytes can then serve as supplementary hepatocytes for further plasma purification.

[0044] This embodiment employs two functionally distinct bioreactors adapted to the physiological characteristics of hepatocytes, ensuring that the in vitro proliferation and metabolism of hepatocytes do not interfere with each other. Optionally, the first bioreactor 31 can be integrated into the corresponding bioartificial liver system to minimize interference with the first bioreactor, while the second bioreactor 41 can be externally connected to the bioartificial liver system via piping for easy disassembly or replacement. The piping connecting the second bioreactor 41 to the system can be the aforementioned hepatocyte recovery piping 42 and bio-supply piping 43, or it can be connected to the hepatocyte recovery piping 42 and bio-supply piping 43 via extended piping.

[0045] In this embodiment, the first inlet 311 and the second inlet 312 in the first bioreactor 31 are arranged opposite to each other within the tank, allowing the raw plasma input from the first inlet 311 and the supplemented hepatocytes input from the second inlet 312 to form a convective turbulent flow inside the first bioreactor 31. This convective turbulent flow facilitates more thorough flow of the solid-liquid mixture or suspended matter inside the first bioreactor, avoiding blind spots in substance exchange. This allows for better purification of the plasma by suspended or semi-suspended hepatocytes.

[0046] In another implementation, the bioregeneration pathway 4 also includes a waste liquid tank 44, which is connected to the hepatocyte outlet 323 of the solid-liquid separator 32 via a waste liquid pipeline 45. Further, a second diverter 46 is installed at the hepatocyte outlet 323 to connect the hepatocyte recovery pipeline 42 and the waste liquid pipeline 45. Since not all hepatocytes are preferably recovered and regenerated after the reaction, the second diverter 46 controls the recovery ratio, and the remaining unrecovered hepatocytes are diverted to the waste liquid tank 44 for temporary storage. In this 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, periodically extracting discarded hepatocytes and their cultures from the waste liquid tank 44 for testing, which can reflect the operational status of the bioartificial liver system to a certain extent. The separated hepatocytes (and their carriers) discharged from hepatocyte outlet 323 are actually in a solid-liquid mixture. The liquid mainly consists of incompletely separated hepatocyte culture. Therefore, the substances discharged through hepatocyte outlet 323 can be used to detect the content of bioactive markers in hepatocytes, the content of toxic substances in residual culture medium, the pH of the culture, dissolved oxygen levels, etc. These detection methods can also be implemented, at least partially, using automated detection equipment. In this case, the waste liquid tank 44 can be part of the automated detection equipment or the location where the bioartificial liver system of this application interfaces with the automated detection equipment. The second diverter 46 is used to adjust the flow rates of the hepatocyte recovery pipeline 42 and the waste liquid pipeline 45 respectively, to control the amount of hepatocytes recovered.

[0047] The flow distribution parameters of the first splitter 39 and the second splitter 46 can be set to fixed values, or they can be adjusted based on feedback data from sensors within the system. Different models of splitters can be selected according to different usage requirements.

[0048] Furthermore, the bioregeneration pathway 4 also includes an oxygenator 47 and / or a temperature controller connected to the biosupply line 43.

[0049] A temperature controller (not shown) provides a stable temperature environment for the bioartificial liver system of this application. When adjusted to a temperature close to that in vivo, it can prevent unnecessary stress on plasma and blood cells in various circulatory pathways, thus avoiding the production of stress products. In addition, a suitable temperature can also maintain the biological activity of hepatocytes and provide a more efficient plasma purification effect.

[0050] One possible implementation is to use an oxygenator 47 containing an oxygen carrier. In blood purification systems, oxygen carriers mainly involve artificial oxygen carriers, which can mimic the function of natural red blood cells and are used to provide oxygen to patients in emergency situations or when transfusion is difficult. Several main oxygen carriers and their usage methods are as follows: Perfluorocarbon (PFC) oxygen carriers; early blood substitutes, but due to their many limitations, the widespread clinical application of PFCs has been greatly restricted. Hemoglobin-modified oxygen carriers; classified according to preparation methods as follows: First generation: mainly including intramolecular and intermolecular cross-linking, polymerization, and recombinant hemoglobin; Second generation: oxygen carriers characterized by cross-linking with certain enzymes; Third generation: microencapsulated type; First and second generation oxygen carriers have oxygen-carrying and oxygen-releasing functions close to those of natural red blood cells and have achieved some clinical application. However, due to their lack of a cell membrane-like barrier, the purity requirements for hemoglobin raw materials are extremely high, and free hemoglobin easily interacts with many active molecules in the blood, inducing a series of abnormal side reactions. Other blood substitutes; hemoglobin oxygen carriers (HBOCs), including polymerized hemoglobin, gene-regulated hemoglobin, and polyethylene glycol (PEG)-modified hemoglobin. These carriers have better stability, do not require blood typing or crossmatching, have a longer circulating half-life, and do not accumulate in relevant 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 hepatocytes and enhancing the purification effect of the bioartificial liver of this application.

[0051] refer to Figure 2 The changes in the whole blood state of receptor 1 using the convective mass exchange bioartificial liver system of this application are as follows:

[0052] Whole blood is separated into protoplasm and blood cells by plasma separator 21. Blood cells are returned to recipient 1. Protoplasm is transported to the convective material exchange zone (first bioreactor 31) to exchange substances with hepatocytes. After the reaction, it is transported to solid-liquid separator 32 to be separated into purified plasma and post-reaction hepatocytes. The purified plasma is divided into two parts: one part is returned to the convective material exchange zone for further purification, and the other part is returned to recipient 1. Post-reaction hepatocytes are also divided into two parts: one part is recycled and regenerated into replenishing hepatocytes, and the other part becomes waste hepatocytes. Replenishing hepatocytes are transported to the convective material exchange zone to exchange substances with protoplasm.

[0053] In summary, a convective material exchange bioartificial liver system includes: a plasma separation pathway, comprising a plasma separator, an arterial conduit connecting the blood inlet of the plasma separator to the recipient artery, and a venous conduit connecting the blood cell outlet of the plasma separator to the recipient vein; a biopurification pathway, comprising a first bioreactor, a solid-liquid separator, a pre-purification conduit connecting the first inlet of the first bioreactor to the original plasma outlet of the plasma separator, a post-purification conduit connecting the purified outlet of the first bioreactor to the separation inlet of the solid-liquid separator, and a return conduit connecting the net plasma outlet of the solid-liquid separator to the venous conduit; and a bioregeneration pathway, comprising a second bioreactor, a hepatocyte recovery conduit connecting the recovery inlet of the second bioreactor to the hepatocyte outlet of the solid-liquid separator, and a biosupply conduit 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 each other in the first bioreactor, thereby creating a convective material exchange state inside the first bioreactor. The bioartificial liver system of this application with convective material exchange forms convective turbulence inside the first bioreactor by controlling the liquid circulation inside the system, thereby accelerating the material exchange inside the first bioreactor and fully utilizing the plasma purification function of suspended or semi-suspended hepatocytes.

[0054] Those skilled in the art will understand that the steps, measures, and solutions in the various operations, methods, and processes discussed in this application can be alternated, modified, combined, or deleted. Furthermore, other steps, measures, and solutions in the various operations, methods, and processes discussed in this application can also be alternated, modified, rearranged, decomposed, combined, or deleted. Furthermore, steps, measures, and solutions in related technologies that are similar to those disclosed in this application can also be alternated, modified, rearranged, decomposed, combined, or deleted.

[0055] In the description of this application, the terms "center," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicate directions or positional relationships based on the exemplary directions or positional relationships shown in the accompanying drawings. They are used to facilitate the description or simplification of the embodiments of this application and are not intended to indicate or imply that the device or component referred to must have a specific orientation or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0056] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, unless otherwise stated, "a plurality of" means two or more.

[0057] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0058] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0059] The above description is only a partial implementation of this application. It should be noted that for those skilled in the art, other similar implementation methods based on the technical concept of this application, without departing from the technical concept of this application, also fall within the protection scope of the embodiments of this application.

Claims

1. A bioartificial liver system for convective material exchange, characterized in that, include: The plasma separation pathway includes a plasma separator, an arterial conduit connecting the blood inlet of the plasma separator to the recipient artery, and a venous conduit connecting the blood cell outlet of the plasma separator to the recipient vein. The biological purification pathway includes a first bioreactor, a solid-liquid separator, a pre-purification pipeline connecting the first inlet of the first bioreactor to the raw plasma outlet of the plasma separator, a post-purification pipeline connecting the purified outlet of the first bioreactor to the separation inlet of the solid-liquid separator, and a return pipeline connecting the purified plasma outlet of the solid-liquid separator to the venous pipeline. The biological regeneration pathway includes 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 each other in the first bioreactor, which causes a convective mass exchange state to occur inside the first bioreactor.

2. The bioartificial liver system with convective material exchange as described in claim 1, characterized in that, The solid-liquid separator employs a membrane separator and / or a centrifugal separator to separate the solid and liquid phases originating from the first bioreactor.

3. The bioartificial liver system for convective material exchange as described in claim 1, characterized in that, 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.

4. The bioartificial liver system with convective mass exchange as described in claim 3, characterized in that, The clean plasma outlet is equipped with a first diverter that connects the return pipeline and the plasma recovery pipeline.

5. The bioartificial liver system for convective material exchange as described in claim 1, characterized in that, The biological purification pathway also includes a body fluid replenishment tank, which merges with the return pipeline or venous pipeline through a replenishment pipeline.

6. The bioartificial liver system for convective material exchange as described in claim 1, characterized in that, The bioregeneration pathway also includes a waste liquid tank, which is connected to the hepatocyte outlet of the solid-liquid separator via a waste liquid pipeline.

7. The bioartificial liver system for convective material exchange as described in claim 6, characterized in that, The hepatocyte outlet is equipped with a second diverter that connects the hepatocyte recovery pipeline and the waste liquid pipeline.

8. The bioartificial liver system for convective material exchange as described in claim 1, characterized in that, The bioregeneration pathway also includes an oxygenator and / or a temperature controller connected to the bio-supply pipeline.

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

10. The bioartificial liver system for convective material exchange as described in claim 1, characterized in that, At least one peristaltic pump is installed on each of the pulping pathway, the biological purification pathway, and the biological regeneration pathway.

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